Hologic ThinPrep Operator's Manual

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ThinPrep® Imaging System

Review Scope Operator’s Manual

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For Use With Version 6.x.y Software

MAN-03352-001

The ThinPrep® Imaging System is a PC-based and automated review system for use with ThinPrep.

cervical cytology sample slides. The ThinPrep

Imaging System is intended to help a cytotechnologist or pathologist highlight areas of a slide for further manual review. The Product is not a replacement for manual review. Determination of slide adequacy and patient diagnosis is at the sole discretion of

the cytotechnologists and pathologists trained by Hologic to evaluate ThinPrep and only if it is finally determined by a court of competent jurisdiction that the Product sold to Cus

prepared slides. If

tomer thereunder was defective in design or contained a manufacturing defect and that such defect was solely responsible for an error in diagnosis that caused harm to a patient, Hologic shall indem

nify Customer for the compensatory damages paid by Customer to discharge the personal injury judgment with respect to Product.

Caution: Federal law restricts this device to sale by or on the order of a physician, or any other practitioner licensed by the law of the State in which the practitioner practices to use or order the use of the device and are trained and experienced in the use of the ThinPrep Imaging System.

© Hologic, Inc., 2017. All rights reserved. No part of this publication may be reproduced, transmitted, transcribed, stored in a retrieval system, or translated into any language or computer language, in any form, or by any means, electronic, mechanical, magnetic, optical, chemical, manual, or other

wise, without the prior written permission of Hologic, 250 Campus Drive, Marlborough, Massachusetts, 01752, United States of America.

Although this guide has been prepared with every precaution to ensure accuracy, Hologic assumes no liability for any errors or omissions, nor for any damages resulting from the application or use of this information.

This product may be covered by one or more U.S. patents identified at http://www.hologic.com/patentinformation/

Hologic, PreservCyt and ThinPrep are registered trademarks in the United States and other countries. All other trademarks are the property of their respective companies.

Changes or modifications to this unit not expressly approved by the party responsible for compliance could void the user’s authority to operate the equipment.

Document Number: AW-09293-001 Rev. 005

Imaging System

The ThinPrep

Imaging System

Operation Summary and Clinical Information

The ThinPrep® Imaging System

A. INTENDED USE

The Hologic ThinPrep® Imaging System (Imager) is a device that uses computer imaging technology to assist in primary cervical cancer screening of ThinPrep Pap Test slides for the presence of atypical cells, cervical neoplasia, including its precur sor lesio ns (Low Grade Sq uamou s Intraepithelial Lesions, High Grade Squamous Intraepithelial Lesions), and carcinoma as well as all other cytologic criteria as defi ned by 2001 B et hesda Sy stem : Term inol ogy for Rep orti ng Re sults of Cervical Cytology

B. SUMMARY AND EXPLANATION OF THE SYSTEM

The ThinPrep Imaging System is an automated imaging and review system for use with ThinPrep Pap Test slides. It combines imaging technology to identify microscopic fields of diagnostic interest with automated stage movement of a microscope in order to locate these fields. In routine use, the ThinPrep Imaging System selects 22 fields of view for a Cytotechnologist to review. Following review of these fields, the Cytotechnologist will either complete the diagnosis if no abnormalities are identified or review the entire slide if any abnormalities are identified. The ThinPrep Imaging System also allows the physical marking of locations of interest for the Cytopathologist.

C. PRINCIPLES OF OPERATION

The ThinPrep Imaging System consists of an Image Processor and one, or more, Review Scopes. The system makes use of computer imaging to select fields of view for presentation to a Cytotechnologist on a Review Scope. Slides used with this system must first be prepared on a ThinPrep 2000 or 3000 Processor, and stained with ThinPr ep Stain.

The Imaging Processor acquires and processes image data from the slides to identify diagnostically relevant cells or cell groups based on an imaging algorithm that considers cellular features and nuclear darkness. During slide imaging, the alphanumeric slide accession identifier is recorded and the x and y coordinates of 22 fields of interest are stored in the computer database. This computer also coordinates the communication of information between the Image Processor and the Review Scopes.

After image processing, slides are distributed to Cytotechnologists for review utilizing the Review Scopes. The Review Scope is a microscope with an automated stage to facilitate the locating of the 22 fields containing the cells of interest. Additionally, the Review Scope provides a method for automated marking of objects for further review. Slides are individually loaded onto the Review Scope stage, the alphanumeric slide accession identifier is automatically scanned and the stored x and y coordinates representing fields of interest for that slide are electronically downloaded from the computer to the Review Scope. The Cytotechnologist then uses a keypad to step through each of the fields of interest (Autolocate). If the Cytotechnologist identifies any of these fields as containing abnormal objects, that field may be marked electronically. The Review Scope will guide the Cytotechnologist to conduct a review of the entire cell spot for any slide that h as had fields electronically marked (Autoscan). The Cytotechnologist determines specimen adequacy and the presence of infections during the review of the 22 fields of view presented by the ThinPrep Imaging System. Either of two method s can be used to determine specimen adequacy. The first method is to count cells and determine the average number of cells in the 22 fields of view presented by the Imager. The second method is to count and determine the average number of cells in 10 fields of view across the diameter of the cell spot. Either method will enable the Cytotechnologist to determine if the minimum cells, as recommended by Bethesda System 2001 criteria, are present on the slide. At the conclusion of the slide review electronically marked objects are automatically ink marked. Any x and y coordinates representing marked locations al ong with a slide com pletion status are then electronically transmitted back to the computer for storage.

MAN-03938-001 Rev. 002 page 2 of 23

D. LIMITATIONS

 Only pers onnel who ha ve bee n approp riately traine d should operat e the ThinPrep® Imaging System

Image Processor or Review Scope.

 All slides that undergo primary automated screening with the Image Processor require manual

rescreening of the selected fields of view by a Cytotechnologist using a Review Scope.

 The ThinPrep Imaging System is only indicated for use with the ThinPrep Pap Test.

 The laboratory Technical Supervisor should establish individual workload limits for personnel using the

ThinPrep Imaging System. The maximum daily limit specified is only an upper limit and should never be used as an expectation for daily productivity or as a performance target.

 The ThinPre p Im aging Sy ste m has n ot bee n pro ven t o be safe or effective at workload levels which

exceed product labeling.

 ThinPrep slides with fiducial marks must be used.  Slides must be stained using the ThinPrep Stain according to the applicable ThinPrep Imaging

System slide staining protocol.

 Slides should be clean and free of debris before being placed on the system.  The slide coverslip should be dry and located correctly.  Slides that are broken or poorly coverslipped should not be used.  Slides used with the ThinPrep Imaging System must contain properly formatted accession number

identification information as described in the operator’s manual.

 Slides once successfully imag ed on the Image Processor cannot be imaged again.  The performance of the ThinPrep Imaging System using slides prepared from reprocessed sample

vials has not been evaluated; therefore it is recommended that these slides be manually reviewed.

E. WARNINGS

 The Imager generates, uses, and can radiate radio frequency energy and may cause interference to

radio communications.

 A Hologic authorized service representative must install the ThinPrep Imaging System.

F. PRECAUTIONS

 Caution should be used when loading and unloading glass slides on the ThinPrep Imaging System

to prevent slide breakage and/or injury.

 Care should be taken to assure that slides are correctly oriented in the ThinPrep Imaging System

cassettes to prevent rejection by the system.

 Partially processed slide cassettes should not be removed from the Image Processor, as data m ay be

lost.

 The Image Processor should be place d on a flat, sturdy surface away from any vibrating machinery

to assure proper operation.

MAN-03938-001 Rev. 002 page 3 of 23

G. PERFORMANCE CHARACTERISTICS

A multi-center, two-armed clinical study was performed over an eleven (11) month period at four (4) cytology laboratory sites within the United States. The objective of the study entitled “MultiCenter Trial Evaluating the Primary Screening Capability of the ThinPrep to show that routine screening of ThinPrep Pap Test slides using the ThinPrep Imaging System is equivalent to a manual review of ThinPrep slides for all categories used for cytologic diagnosis (specimen adequacy and descriptiv e diagnosis) as defined by the Bethesda System criteria

The two-arm study approach allowed a comparison of the cytologic interpretation (descriptive diagnosis and specimen adequacy) from a single ThinPrep prepared slide, screened first using standard laboratory cervical cytology practices (Manual Review) and then after a 48 day time lag were screened with the assistance of the ThinPrep Imaging System (Imager Review). A subset of slides from the study were reviewed and adjudicated by a panel of three (3) independent Cytopathologists to determine a consensus diagnosis. The consensus diagnosis was used as a “gold standard” for truth to evaluate the results of the study.

G.1 LABORATORY AND PATIENT CHARACTERISTICS

Of the 10,359 subjects in the study, 9,550 met the requirements for inclusion in the descriptive diagnosis analysis. During the study, 7.1% (732/10,359) slides could not be read on the Imager and required a manual review during the Imager Review arm. Excessive number of air bubbles on the slides was the leading contributor. Additional factors included focus pr oblems, slide density, slide identification read failures, slides detected out of position, multip le slides seated within a cassette slot and slides that had already been imaged. The cytology laboratories participating in the study were comprised of four centers. All sites selected had extensive experience in the processing and evaluation of gynecologic ThinPrep slides, and were trained in the use of the ThinPrep Imaging System. The study population represented diverse geographic region s and subject populations of women who would undergo cervical screening with the ThinPrep Imaging System in normal clinical use. These sites included both women being routinely screened (screening population) and patients with a recent previous cervical abnormality (referral population) . The characteristics of the study sites are summarized in Table 1.

Table 1: Site Characteristics

Imaging System” was

Site 1 2 3 4

Low Risk Population

High Risk Population

HSIL+ prevalence

ThinPrep Pap Tests Per Year

Number of Cytotechnologists

Number of Cytotechnologists in Study

Number of Cytopathologists

Number of Cytopathologists in Study

88% 82% 90% 94%

12% 18% 10% 6%

1.1% 0.7% 0.4% 0.6%

120,000 70,200 280,000 105,000

14 9 32 11

2 2 2 2

6 5 6 14

1 2 1 2

MAN-03938-001 Rev. 002 page 4 of 23

G.2 DESCRIPTIVE DIAGNOSIS SENSITIVITY AND SPECIFICITY ESTIMATES

A panel of three independent Cytopathologists adjudicated slides from all discordant (one-grade or higher cytologic difference) descriptive diagnosis cases (639), all concordant positive cases (355) and a random 5% subset of the 8550 negative concordant cases (428). The Cytopathologists on the adjudication panel were board-certified, all of whom had a subspecialty certification in Cytopathology. Their experience levels in Cytopathology ranged from 6 to 12 years. Two of the adjudicators were from university practices and one adjudicator was from a private medical center. The volumes for the adjudicator’s institutions ranged from 12,0 00 to 30,000 ThinPrep annually.

A consensus diagnosis was defi ned as agreement by at least 2 of 3 Cytopathologists. All sli des sent to the panel of Cytopathologists were not identified by site nor ordered in any fashion. When a consensus diagnosis could not be obtained by at least 2 of 3 Cytopathologists, the full panel of Cytopathologists reviewed each case simul taneously usin g a mult i-headed mi croscope to determ ine a consensus diagnosis.

The adjudicated results were used as a “gold standard” to define the following major “true” descriptive diagnosis classifications of the Bethesda System: Negative, ASCUS, AGUS, LSIL, HSIL, Squamous Cell Carcinoma (SQ CA) and Glandular Cell Carcinoma (GL CA). Estimates of sensitivity and specificity together with 95% confidence intervals were calculated for the Manual Review and Imager Review arms of the study. The differences in sensitivity and specificity between the two arms, together with their 95% confidence intervals were also calcu lated. Among the random 5% subset of 8,550 cases (428 slides) that were found to be negative by both arms and adjudicated, there were 425 “true” negative and 3 “true” ASCUS slides. A multiple imputation technique was used to adjust the numbers of true positives and true negatives for the 8,550 negative concord ant cases based on the 5% of cases that were adjudicated

Pap Tests

Tables 2-4 below summarize the descriptive diagnosis sensitivity and specificity estimates with 95% confidence intervals for each of the four sites and all sites combined for “true” ASCUS+, LSIL+ and HSIL+.

Table 2: Adjudicated Review Versus Imager And Manual Reviews ASCUS+ Descriptive Diagnosis Summary.

Sensitivity is a percent of “true” ASCUS+ (combined ASCUS, AGUS, LSIL, HSIL, SQ CA and GL CA) slides classified in either study arm as ASCUS+ and specificity is a percent of “true” Negative slides classified in either study arm as Negative.

Sensitivity Specificity

Site/

Number

Cases Site 1 180 Site 2 230 Site 3 103 Site 4 179 All 692

Numbers in parentheses represent 95% confidence intervals.

Manual Imager Difference

77.2%

(70.4, 83.1)

63.1%

(56.5, 69.3)

80.6%

(71.6, 87.7)

87.2%

(81.4, 91.7)

75.6%

(72.2, 78.8)

78.3%

(71.6, 84.1)

77.5%

(71.4, 82.6)

94.2%

(87.8, 97.8)

84.4%

(78.2, 89.4)

82.0%

(78.8, 84.8)

+1.1%

(-5.8, 8.0)

+14.4%

(8.2, 20.5)

+13.6%

(4.3, 22.9)

-2.8%

(-10.6, 5.0)

+6.4%

(2.6, 10.0)

Site/

Number

Cases Site 1 2132 Site 2 2210 Site 3 2196 Site 4 2313 All 8851

Manual Imager Difference

98.7%

(98.1, 99.1)

95.8%

(94.9, 96.6)

98.5%

(97.9, 99.0)

97.3%

(96.6, 97.9)

97.6%

(97.2, 97.9)

99.2%

(98.7, 99.5)

96.1%

(95.2, 96.9)

98.8%

(98.3, 99.2)

97.0%

(96.2, 97.7)

97.8%

(97.4, 98.1)

+0.4%

(-0.1, 1.0)

+0.3%

(-0.7, 1.3)

+0.4%

(-0.3, 1.0)

-0.3%

(-1.1, 0.5)

+0.2%

(-0.2, 0.6)

The results presented in Table 2 show that for ASCUS+, the increase in sensitivity of the Imager Review over the Manual Review was statistically significant with the lower limit of the 95% confidence interval being 2.6% for all sites combined. The observed difference between sensitivities for ASCUS+ varied among the sites from –2.8% with a 95% confi dence int erval of (–10.6%; 5.0%) to +14.4% with a 95% confidence interval of (8.2%; 20.5%) . The difference in specificity results between the Imager Review and the Manual Review was not statistically significant with a 95% confidence interval of -0.2% to +0.6%. The observed differences between specificities varied am ong the sites from –0.3% to +0.4%.

MAN-03938-001 Rev. 002 page 5 of 23

Table 3: Adjudicated Review Versus Imager Review LSIL+ Descriptive Diagnosis Summary for Each Site and All Sites Combined.

Sensitivity is a percent of “true” LSIL+ (combined LSIL, HSIL, SQ CA and GL CA) slides classified in either study arm as LSIL+ and specificity is a percent of “true” Non-LSIL+ (combined Negative, ASCUS, AGUS) slides classified in either study arm as Non-LSIL+.

Sensitivity Specificity

Site/

Number

Cases Site 1 104 Site 2 98 Site 3 62 Site 4 111 All 375

Numbers in parentheses represent 95% confidence intervals.

Manual Imager Difference

84.6%

(76.2, 90.9)

70.4%

(60.3, 79.2)

77.4%

(65.0, 87.1)

84.7%

(98.1, 99.1)

79.7%

(75.3, 83.7)

82.7%

(74.0, 89.4)

72.4%

(62.5, 81.0)

85.5%

(74.2, 93.1)

78.4%

(76.6, 90.8)

79.2%

(74.7, 83.2)

-1.9%

(-9.5, 5.6)

+2.0%

(-6.9, 11.0)

+8.1%

(-4.0, 20.1)

-6.3%

(-14.7, 2.1)

-0.5%

(-5.0, 4.0)

Site/

Number

Cases Site 1 2208 Site 2 2342 Site 3 2237 Site 4 2381 All 9168

Manual Imager Difference

98.7%

(98.1, 99.1)

99.3%

(98.8, 99.6)

99.2%

(98.7, 99.5)

98.7%

(98.2, .99.2)

99.0%

(98.8, 99.2)

99.3%

(98.9, 99.6)

98.9%

(98.4, 99.3)

99.5%

(99.1, 99.8)

98.7%

(98.1, 99.1)

99.1%

(98.9, 99.3)

+0.6%

(0.1, 1.0)

-0.4%

(-0.8, .001)

+0.3%

(-0.1, 0.6)

-0.08%

(-0.6, 0.4)

+0.09%

(-0.1, 0.3)

The results presented in Table 3 show that the difference between sensitivities of the Imager Review and Manual Review arms for LSIL+ for all sites co mbined was not statistically significant with a 95% confidence interval of –5.0% to +4.0%. The observed difference between sensitivities for LSIL+ varied among the sites from –6.3% with a 95% confidence interval of (–14.7%; 2.1%) to +8.1% with a 95% confidence interval of (–4.0%; 20.1%). The difference in specificity results between the Imager Review and the Manual Review was not statistically significant with a 95% confidence interval of -0.1% to +0.3%. The observed differences between specificities varied am ong the sites from –0.4% to +0.6%.

Table 4: Adjudicated Review Versus Imager Review HSIL+ Descriptive Diagnosis Summary for Each Site and All Sites Combined.

Sensitivity is a percent of “true” HSIL+ (combined HSIL, SQ CA and GL CA) slides classified in either study arm as HSIL+ and specificity is a percent of “true” Non-HSIL+ (combined Negative, ASCUS, AGUS, LSIL) slides classified in either study arm as Non-HSIL+.

Sensitivity Specificity

Site/

Number

Cases Site 1 38 Site 2 40 Site 3 22 Site 4 39 All 139

Numbers in parentheses represent 95% confidence intervals.

Manual Imager Difference

89.5%

(75.2, 97.1)

72.5%

(56.1, 85.4)

72.7%

(49.8, 89.3)

61.5%

(44.6, 76.6)

74.1%

(66.0, 81.2)

92.1%

(78.6, 98.3)

70.0%

(53.4, 83.4)

86.4%

(65.1, 97.1)

74.4%

(57.9, 87.0)

79.9%

(72.2, 86.2)

2.6%

(-8.9, 14.1)

-2.5%

(-15.4, 10.4)

+13.6%

(-0.7, 28.0)

+12.8%

(-1.7, 27.4)

+5.8%

(-1.1, 12.6)

Site/

Number

Cases Site 1 2274 Site 2 2400 Site 3 2277 Site 4 2453 All 9404

Manual Imager Difference

98.8%

(98.3, 99.2)

99.8%

(99.5, 99.9)

99.7%

(99.4, 99.9)

99.5%

(99.2, 99.8)

99.4 %

(99.2, 99.6)

99.5%

(99.1, 99.8)

99.6%

(99.2, 99.8)

99.7%

(99.4, 99.9)

99.8%

(99.5, 99.9)

99.6%

(99.5, 99.7)

+0.7%

(0.2, 1.2)

-0.1%

(-0.3, .09)

(-0.2, 0.2)

+0.3%

(-0.003, 0.6)

+0.2%

(0.06, 0.4)

MAN-03938-001 Rev. 002 page 6 of 23

The results presented in Table 4 show that the difference between sensitivities of the Imager Review and Manual Review arms for HSIL+ for all sites combined was not statistically significan t with a 95% confidence interval of -1.1% to +12.6%. The observed difference between sensitivities for HSIL+ varied among the sites from –2.5% with a 95% confidence interval of (–15.4%; 10.4%) to +13.6% with a 95% confidence interval of (–0.7%; 28.0%). The increase in specificity of the Imager Review over the Manual Review was statistically significant with a 95% confidence interval of +0.06% to +0.4%. The observed differences between specificities varied among the sites from –

0.1% to +0.7%. Tables 5-9 show the performance of the Imager Review and Manual Review compared to the final

consensus diagnosis made by the adjudication panel (truth) for the following major descriptive diagnosis classifications of the Bethesda System: Negative, ASCUS, AGUS, LSIL, HSIL, Cancer* (CA)

*Includes SQ CA and GL CA.

Abbreviations for Diagnoses: NEG = Normal or negative, ASCUS = Atypical Squamous Cells of Undetermined Significance,

AGUS = Atypical Glandular Cells of Undetermined Significance, LSIL = Low-grade Squamous Intraepithelial Lesion, HSIL = High-grade Squamous Intraepithelial Lesion, SQ CA = Squamous Cell Carcinoma, GL CA = Glandular Cell Adenocarcinoma.

All 786 Cases Determined To Be Negative By Adjudication

Table 5: 6x6 “True Negative” Contingency Table For All Sites Combined

Unadjudicated Manual Review Arm Diagnosis

NEG ASCUS AGUS LSIL HSIL CA TOTAL NEG 425 138 6 10 6 2 587 ASCUS 130 39 1 3 - - 173 AGUS 5 - - - - - 5 LSIL 9 5 - 2 - - 16 HSIL 1 1 - - 3 - 5 CA - - - - - - 0

Unadjudicated Imager

Review Arm Diagnosis

TOTAL 570 183 7 15 9 2 786

Among the 786 cases determined by the adjudication panel to be Negative, 587 (74.7%) cases in the Imager Review arm and 570 (72.5%) cases in the Manual Review arm were diagnosed as Negative and 21 (2.7%) cases in the Imager Review arm and 26 (3.3%) cases in the Manual Review arm were diagnosed as LSIL+.

Table 6: 6x6 “True ASCUS” Contingency Table For All Sites Combined

All 251 Cases Determined To Be ASCUS By Adjudication

Unadjudicated Manual Review Arm Diagnosis

NEG ASCUS AGUS LSIL HSIL CA TOTAL NEG 3 32 - 7 3 - 45 ASCUS 70 47 1 20 4 - 142 AGUS 1 - - - - - 1 LSIL 6 21 - 16 7 - 50 HSIL 2 3 - 5 1 1 12 CA 1 - - - - - 1

Unadjudicated Imager

Review Arm Diagnosis

TOTAL 83 103 1 48 15 1 251

Among the 251 cases determi ned by the adjudication panel to be ASCUS, 142 (56.6%) cases in the Imager Review arm and 103 (41.0%) cases in the Manual Review arm were diagnosed as ASCUS and 45 (17.9%) cases in the Imager Review arm and 83 (33.1%) cases in the Manual Review arm were diagnosed as Negative.

MAN-03938-001 Rev. 002 page 7 of 23

Table 7: 6x6 “True AGUS” Contingency Table For All Sites Combined

All 10 Cases Determined To Be AGUS By Adjudication

Unadjudicated Manual Review Arm Diagnosis

NEG ASCUS AGUS LSIL HSIL CA TOTAL NEG - 2 1 - 1 - 4 ASCUS - - 1 - - - 1 AGUS 2 - 1 - - 1 4 LSIL - - - - - - 0 HSIL - - - - - - 0 CA - - - - - 1 1

Unadjudicated Imager

Review Arm Diagnosis

TOTAL 2 2 3 0 1 2 10

Among the 10 cases determined by the adjudication panel to be AGUS, 4 (40.0%) cases in the Imager Review arm and 3 (30.0%) cases in the Manual Review arm were diagnosed as AGUS and 4 (40.0%) cases in the Imager Review arm and 2 (20.0%) cases in the Manual Review arm were diagnosed as Negative.

Table 8: 6x6 “True LSIL” Contingency Table For All Sites Combined

All 236 Cases Determined To Be LSIL By Adjudication

Unadjudicated Manual Review Arm Diagnosis

NEG ASCUS AGUS LSIL HSIL CA TOTAL NEG - 4 - 12 1 - 17 ASCUS 13 16 - 20 1 - 50 AGUS - - - - - - 0 LSIL 8 20 - 115 12 - 155 HSIL - - - 5 9 - 14 CA - - - - - - 0

Unadjudicated Imager

Review Arm Diagnosis

TOTAL 21 40 0 152 23 0 236

Among the 236 cases determined by the adjudication panel to be LSIL, 155 (65.6%) cases in the Imager Review arm and 152 (64.4%) cases in the Manual Review arm were diagnosed as LSIL and 17 (7.2%) cases in the Imager Review arm and 21 (8.9%) cases in the Manual Review arm were diagnosed as Negative.

Table 9: 6x6 “True HSIL” Contingency Table For All Sites Combined

All 138 Cases Determined To Be HSIL By Adjudication

Unadjudicated Manual Review Arm Diagnosis

NEG ASCUS AGUS LSIL HSIL CA TOTAL NEG - 1 - - 1 - 2 ASCUS 2 4 - 2 1 - 9 AGUS - - - - - - 0 LSIL 1 - - 10 6 - 17 HSIL 3 3 1 9 91 1 108 CA - - - - 1 1 2

Unadjudicated Imager

Review Arm Diagnosis

TOTAL 6 8 1 21 100 2 138

MAN-03938-001 Rev. 002 page 8 of 23

Among the 138 cases determined by the adjudication panel to be HSIL, 108 (78.3%) cases in the Imager Review arm and 100 (72.5%) cases in the Manual Review arm were diagnosed as HSIL and 2 (1.4%) cases in the Imager Review arm and 6 (4.3%) cases in the Manual Review arm were diagnosed as Negative.

There was one (1) squamous cell carcinoma (SQ CA) case resulting from adjudication. It was diagnosed as HSIL in the Imager Review arm and SQ CA in the Manual Review arm.

Table 10 shows the study subjects unadjudicated descriptive diagnosis marginal frequencies for benign cellular changes for all sites combined.

Table 10: Unadjudicated Marginal Frequencies Summary of Descriptive Diagnosis for Benign Cellular Changes – All Sites Combined.

Manual Review Imager Review

Number of Patients: 9550 9550

Descriptive Diagnosis N % N %

Benign Cellular Changes:

Infection:

Trichomonas Vaginalis 8 0.1 8 0.1 Fungal organisms consistent with Candida spp. 47 0.5 31 0.3 Predominance of coccobacilli 71 0.7 60 0.6 Bacteria consistent with Actinomyces spp. 1 0.0 1 0.0 Cellular Changes associated with Herpes virus 1 0.0 1 0.0 Other Infection 1 0.0 0 0.0

Reactive Cellular Changes Associated with:

Inflammation 218 2.3 156 1.6 Atrophic with inflammation (atrophic vaginitis) 68 0.7 46 0.5 Radiation 0 0.0 0 0.0 Intrauterine contraceptive device (IUD) 0 0.0 0 0.0 Other Reactive Cellular Change 34 0.4 14 0.1

Note: Some patients had more than one diagnostic subcategory.

405 4.2 293 3.1

The Manual Review showed a higher rate of Benign Cellular Changes (405) than the Imager Review cases (293).

G.3 ANALYTICAL PERFORMANCE OF THINPREP IMAGING SYSTEM FOR DETECTION OF CERVICAL CANCER USING THINPREP

PAP TEST SLIDES

FRESHLY PREPARED FROM ARCHIVAL SAMPLES

This analytical study was conducted to compare the Bethesda System 2001 results, obtained by a Cytotechnologist and a Cytopathologist, when their review was limited to 22 fields that were selected by the ThinPrep Imaging System, to their diagnostic results obtained from their independent blinded review of the entire cell spot on the ThinPrep Pap Test slides. All of the reviews were performed in an independent and blinded manner. The test materials consisted of 33 archival PreservCyt-preserved cervical samples that had been previously diagnose d a s AG US o r cancer . One ThinPrep Pap Test slide was freshly prepared from each of the 33 original PreservCyt vials. All of the ThinPrep slides used in the study were made on the TP-2000 processor and stained with ThinPrep Stain. Based on the cur rent cervical cancer prevalence rate in the United States, 33 cases of cervical cancer would represent the number of invasive cervical cancer cases in a population of approximately 275,000 women

Initially, a board-certified Cytopathologist manually reviewed all of the fields on the ThinPrep Pap Test slides and identified and recorded the number of individual cancer cells and clusters of cancer cells that were present. For this part of the study, the Cytopathologist was not required to record any other cells with other Bethesda System 2001 diagnoses. The 33 cases included slides that represented both rare numbers of cancer cells (5-20 per slide), and numerous cancer cells (>20/slide). Cancer cells were categorized according to Bethesda System 2001 criteria for Glandular Cancer, Ade nocarcinom a-in-situ and Squamous Cell Cancer. Each slide was then processed on a ThinPrep Imaging System. The Cytotechnologist then reviewed only the 22 fields of view presented by the Autolocate mode of the Review Scope. No review outside of the selected 22 fields of view was permitted. For each field of view, the Cytotechnologist counted and recorded all abnormal cell types based on the following seven Bethesda System classifications: ASCUS, LSIL, HSIL, AGUS, Glandular Cancer, Squamous Cell Carcinoma and Adenocarcinoma-In-Situ.

MAN-03938-001 Rev. 002 page 9 of 23

Finally, the same Cytopathologist who had conducted the manual review of the entire ThinPrep

Pap Test slide, independently re-reviewed the slides using the identical method used by the Cytotechnologists. The Cytopathologist was blinded from the original manual review results. For each of the 22 fields of view selected by the ThinPrep Imaging System, the Cytopathologist verified and recorded the number of individual cancer cells, clusters of cancer cells, and any other abnormalities present. Table 11 summarizes the results from this study:

Table 11: Summary of Results From Restricted Analytical Cancer Study

Cytopathologist Full Manual

Review

10 Glandular Cancer

1 Adenocarcinoma In-situ 1 Adenocarcinoma In-Situ 1 Adenocarcinoma In-Situ

22 Squamous Cell Carcinoma

Total = 33 Total = 33 Total = 33

Cytotechnologist Review of Imager

Identified 22 Fields of View *

5 Glandular Carcinoma 1 Squamous Cell Carcinoma 1 Adenocarcinoma In-situ 2 HSIL/AGUS 1 ASC-H/ASC-US

3 Glandular Carcinoma 12 Squamous Cell Carcinoma 1 Squamous/Glandular Carcinoma 2 Adenocarcinoma In-situ 4 HSIL

Cytopathologist Review of

Imager Identified 22 Fields

of View **

7 Glandular Carcinoma 1 Squamous Cell Carcinoma 1 AGUS 1 HSIL

21 Squamous Cell Carcinoma 1 Adenocarcinoma In-situ

* In the intended use of the ThinPrep Imaging System (Imager), the Cytotechnologist would perform a full manual slide review

of each of these cases and pass them on to a Cytopathologist for further review.

* *In the intended use of the ThinPrep Imaging System (Imager), the Cytopathologist would perform a full manual slide review of

each of these cases.

The results in Table 11 demonstrate the ability of the ThinPrep Imaging System to successfully identify abnormalities in the 22 fields of view presented during the Autolocate mode of slide review. In all 33 cases in this study, the ThinPrep Imaging System identified and presented cells among the 22 fields of view that were categorized as Cancer, HSIL, AGUS or ASCUS. In addition, the Cytopathologists’ confirming review of the identical 22 fields of view showed consistent, but slightly improved results with all cases being categorized as Cancer, HSIL or AGUS. Consistent with the intended use of the ThinPrep Imaging System, the Cytotechnologists’ diagnoses in every one of these 33 cas es would have invoked the full slide Autoscan mode that would require a Cytotechnologist to screen the entire slide before making a final diagnosis. The results of this study indicate that ThinPrep Imaging System will accurately lead to a full manual slide review for the detection of cervical cancer or its precursor lesi ons.

G.4 SPECIMEN ADEQUACY STUDY

Of the 10,359 subjects in the study, 9627 met the requirements for inclusion in the specimen adequ acy analysis.

MAN-03938-001 Rev. 002 page 10 of 23

Table 12: Unadjudicated Marginal Frequencies Summary of Specimen Adequacy Results – All Sites Combined.

Manual Review Imager Review

Number of Patients:

Descriptive Diagnosis N % N %

Satisfactory for Evaluation Satisfactory but Limited by

Endocervical Component Absent 1196 12.4 1397 14.5 Scant Squamous Epithelial Component 92 1.0 102 1.1 Obscuring Blood 45 0.5 17 0.2 Obscuring Inflammation 69 0.7 68 0.7 No Clinical History 982 10.2 933 9.7 Cytolysis 4 0.0 2 0.0 Other 6 0.1 33 0.3

Unsatisfactory for Evaluation

Endocervical Component Absent 6 0.1 0 0.0 Scant Squamous Epithelial Component 35 0.4 22 0.2 Obscuring Blood 17 0.2 2 0.0 Obscuring Inflammation 8 0.1 5 0.1 No Clinical History 2 0.0 2 0.0 Cytolysis 0 0.0 0 0.0 Other 2 0.0 0 0.0

Note: Some patients had more than one diagnostic subcategory.

9627 9627

7375 76.6 7346 76.3 2186 22.7 2252 23.4

66 0.7 29 0.3

For SAT cases, there was agreement between the Manual Review cases (7375) and the Imager Review cases (7346). For SBLB cases, there is agreement between the Manual Review cases (2186) and the Imager Review cases (2252). Unsatisfactory cases were greater in the Manual Review cases (66) versus the Imager Review cases (29).

The adjudicated results were used as a “gold standard” to define “true” specimen adequacy classifications of the Bethesda System: SAT/SBLB and UNSAT. There were 58 “true” UNSAT cases and 9569 “true” SAT/SBLB cases.

Table 13 below summarizes specimen adequacy performance for the Imager Review and Manual Review arms for all four sites and all sites combined using the Bethesda System 1991 criteria.

Table 13: Adjudicated Review Versus Imager Review Specimen Adequacy Summary for All Sites and All Sites Combined.

Sensitivity is a percent of “true” UNSAT slides classified in either study arm as UNSAT and specificity is a percent of “true” SAT/SBLB slides classified in either study arm as SAT/SBLB.

Sensitivity Specificity

Site/

Number

Cases Site 1 21 Site 2 6 Site 3 5 Site 4 26

All 58 CI*

*95% Confidence Interval

Manual Imager Difference

(0/21)

100%

(6/6)

80.0%

(4/5)

30.8%

(8/26)

29.3%

(17/58)

(18.1, 42.7)

(0/21)

16.7%

(1/6)

60.0%

(3/5)

19.2%

(5/26)

13.8%

(8/58)

(6.1, 25.4)

0.0%

(0/21)

-83.3%

(-5/6)

-20.0%

(-1/5)

-11.5%

(-3/26)

-15.5%

(-9/58)

(-25.9, -5.0)

All ThinPrep

slides that produced discordant unsatisfactory determinations (Manual Review arm

Site/

Number

Cases Site 1 2292 Site 2 2476 Site 3 2323 Site 4 2478

All 9569 CI*

Manual Imager Difference

100%

(2292/2292)

98.9%

(2449/2476)

99.2%

(2304/2323)

99.9%

(2475/2478)

99.5%

(9520/9569)

(99.3, 99.6)

100%

(2292/2292)

99.6%

(2465/2476)

99.7%

(2315/2323)

99.9%

(2476/2478)

99.8%

(9548/9569)

(99.7, 99.9)

0.0%

(0/2292)

+0.6%

(16/2476)

+0.5%

(11/2323)

+0.04%

(1/2478)

+0.3%

(28/9569)

(0.2, 0.4)

MAN-03938-001 Rev. 002 page 11 of 23

vs. Imager Review arm) during the clinical study were assessed in an additional clinical support study to compare the method used for specimen adequacy in the clinical study with a control cell count of the slides and 3 differ ent methods as foll ows: (1) Manual assessment of specim en adequacy on the entire microscope slide based on ThinPrep Bethesda System 1991 criteria; (2) Using the “diameter” method of Bethesda Syst em 2001, which requi res that t he Cyt otechn ologi st c ounts cel ls in 10 fields of view along the diameter of the cell spot and calculate the number of cells on the slide; (3) Having the Cytotechnologist count the cells in the 22 fields o f view pre sented by t he system and calculate the number of cells on the slide.

This additional support study demonstrated that the Bethesda System 1991 estimation methods, including the method used in the clinical study, do not generate similar specimen adequacy determinations when compared against each other or with the control method. Therefore, the recommended methods for determining specimen adequacy on the ThinPrep Imaging System are (1) the Bethesda System 2001 count of fields along a diagonal of the cell spot or (2) counting the cells in the 22 fields-of-view selected by the ThinPrep Imager System. Refer to the ThinPrep Imaging System Review Scope Operator’s Manual for instructions on the proper use of these methods.

G.5 CYTOTECHNOLOGIST SCREENING RATES

Daily Cytotechnologist screening rates were recorded throughout the duration of the clinical study. The study was conducted in a manner designed to reproduce actual clinical conditions. Eight (8) Cytotechnologists participated in the study; two (2) at each clinical site. The experience levels of the Cytotechnologists ranged from 5 to 23 y ears. During the study the Cytotechnologist’s screening times for the Imager Review arm included automated screening of the 22 fields of view with subsequent full side review of abnormal slides. A full slide review co nsists of approximately 120 fields of view. The number of hours each Cytotechnologist screened slides per day varied due to logistical issues and scheduling. With the ThinPrep Imaging System, Cytotechnologist screening rates were uniformly faster than the Manual Review method.

Table 14 summarizes the Cytotechnologist screening rates for both the Imager Review and the Manual Review methods. The total number of slides reviewed in the study and the average number

of hours screened per day are presented for each Cytotechnologist and site. Screening rates (extrapolated to an 8 hour wo rkday) are pres ented as the low, average and high daily screening rates achieved by each Cytotechnologist and site. The low and high daily rates were selected from the lowest and highest daily hourly rates, respectively, and are extrapolated to 8 hours.

MAN-03938-001 Rev. 002 page 12 of 23

Table 14: Cytotechnologist Screening Rates

Site/CT

Review

Methods

Site 1 Manual 2568 7.4 49 69 94

1-1 Manual 1284 7.5 49 60 72

1-2 Manual 1284 7.3 70 78 94

Site 2 Manual 2686 7.7 40 68 80

2-1 Manual 1348 7.6 40 71 80

2-2 Manual 1338 7.8 55 66 75

Site 3 Manual 2738 7.9 20 80 101

3-1 Manual 1368 7.9 63 82 91

3-2 Manual 1370 7.8 20 78 101

Site 4 Manual 2612 7.6 42 69 94

4-1 Manual 1305 8.2 59 75 84

4-2 Manual 1307 6.9 42 63 94

Table 15 summarizes the Manual Review versus the Imager Review for ASCUS+ and HSIL+ sensitivity and specificity by site. The table also presents the prevalence of ASCUS+, LSIL+, and HSIL+ among the reviewed slides and the respective screening daily rates of each review method. The daily screening rates are extrapolated to an 8-hour workday and are presented as the low, average and high daily screening rates by site.

Table 15: Screening Rates, Prevalence of ASCUS+, LSIL+, HSIL+, and Respective Performance for ASCUS+ and HSIL+.

Site % of

ASCUS+

Site 1 7.7% 4.5% 1.6%

Site2 9.2% 4.0% 1.6%

Site 3

Site 4 7.2% 4.5% 1.6%

4.4% 2.7% 1.0%

% of

LSIL+

% of

HSIL+

Total

Number of

Slides

Evaluated

Average

Number of

Hours

Screened Per

Extrapolated Daily Rates

(8-hour workday)

Low Day

Average

Day

High

Day

Imager 2297 6.0 107 153 206

Imager 1168 6.1 117 153 182

Imager 1129 5.9 107 154 206

Imager 2665 7.8 69 109 131

Imager 1309 7.9 97 110 118

Imager 1356 7.7 69 109 131

Imager 2726 4.5 148 204 320

Imager 1460 4.2 167 230 320

Imager 1266 4.7 148 178 212

Imager 2524 5.1 86 138 198

Imager 1252 5.1 86 150 190

Imager 1272 5.0 109 126 198

Review

Methods

Manual 49 69 94 77.2%

Imager 107 153 206 78.3% 99.2% 92.1% 99.5%

Manual 40 68 80 63.1%

Imager 69 109 131 77.7% 96.1% 70.0% 99.6%

Manual 20 80 101 80.6%

Imager 148 204 320 94.2% 98.8% 78.6% 99.7%

Manual 42 69 94 87.2%

Imager 86 138 198 84.4% 97.0% 74.4% 99.8%

Extrapolated Daily Rates

(8-hour workday)

Low Day

Average

Day

High

Day

Performance for

ASCUS+

Sensitivity Specificity Sensitivity Specificity

98.7%

+1.1%

+14.4%

+13.6%

-2.8%

95.8%

98.5%

97.3%

+0.4%

+0.3%

+0.4%

-0.3%

89.5%

72.5%

64.3%

61.5%

Performance for

HSIL+

98.8%

+2.6%

99.8%

-2.5%

99.7%

+13.6%

99.5%

+12.8%

+0.7%

-0.1%

+0.3%

The clinical study data show that the screening rates achieved with the ThinPrep® Imaging System resulted in sensitivity or specificity values that fall within acceptable limits.

MAN-03938-001 Rev. 002 page 13 of 23

Laboratorians should use the following method when calculating workload:

 All slides with Fields of View (FOV) only review count as 0.5 or ½ slide  All slides with full manual review (FMR) using the Autoscan feature count as 1 slide (as mandated by CLIA’88 for

manual screening)

 Then, slides with both FOV and FMR count as 1.5 or 1½ slides  Use these values to count workload, not exceeding the CLIA maximum limit of 100 slides in no less than an 8-hour

day.

FMR = 1 slide

FOV = 0.5 slide

FMR + FOV = 1.5 slides

Upper Limit = 100 slides

The ThinPrep

 Screening 22 Fields of View  Full manual slide review using the Autoscan feature  Review clinical history  Record results and triage appropriately

An example of workload scenario for ThinPrep Pap slides using the ThinPrep Imaging System: 100 FOV review only = 50 slides (100 x 0.5 = 50) 30 FOV review + FMR = 45 slides (30 x 1.5 = 45) Total number of slides screened = 95 (50 FOV only and 45 FOV + FMR)

 Note: ALL laboratories should have a clear standard operation procedure for documentation of their method of workload

counting and for establishing workload limits.

 It is the responsibility of the Technical Supervisor to evaluate and set workload limits for individual cytotechnologists

based on laboratory clinical performance.

According to CLIA ’88, these workload limits should be reassessed every six months.

Imaging System limit of 100 slides in an 8-hour workday includes the following:

For less than an 8-hour workday, the following formula must be applied to determine the maximum number of slides to be reviewed during that workday:

󰇧

The manual workload limit does not supercede the CLIA requirement of 100 slides in a 24-hour period in no less than an 8-hour day. Manual review includes the following types of slides:

 Slides reviewed on the ThinPrep Imaging System using the Autoscan feature  Slides reviewed without the ThinPrep Imaging System  Non–gynecologic slides.

When conducting manual review, refer to the CLIA requirements for calculating workload limits.

G.6 THINPREP IMAGING SYSTEM USE WITH THINPREP 5000 PROCESSOR

A study was conducted to estimate the Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA) for Imager-assisted review as compared with manual review of specimens processed on the ThinPrep 5000 processor.



󰇨100

MAN-03938-001 Rev. 002 page 14 of 23

Clinical Study Design

The study was a prospective, multi-center, blinded evaluation of ThinPrep slides of known diagnoses generated from residual cytological specimens which were prepared, reviewed and adjudicated in a previous study.

One thousand two hundred sixty (1260) slides were prepared on a ThinPrep 5000 processor and were reviewed independently by a Cytotechnologist and confirmed by a Pathologist. All cytologic diagnoses were determined in accordance with the Bethesda System 2001 c riteria for all slides study was conducted at Hologic, Inc., Marlborough, MA and at two external laboratories in the United States.

Table 16: Laboratory Imager-Assisted Review Diagnosis vs. Laboratory Manual Review Diagnosis by one Pair of Cytotechnologist/Pathologist (Combined Sites)

Lab ImagerAssisted Review Diagnosis

UNSAT 30 10 2 0 1 0 0 0 43 NILM 10 620 36 1 5 5 3 1 681 ASC-US 3 40 35 10 8 1 2 0 99 AGUS 0 10 28 127 8 0 8 0 181 LSIL 0 4 9 4 14 2 13 0 46 ASC-H 2 2 1 0 1 3 1 2 12 HSIL 1 3 6 15 24 2 111 5 167 Cancer 1 0 0 0 1 1 7 21 31

Total 47 689 117 157 62 14 145 29 1260

UNSAT NILM ASC-US AGUS LSIL ASC-H HSIL Cancer Total

Lab Manual Review Diagnosis

. The

Reference Diagnosis by Adjudication Review

All slides were subject to an adjudication review. Adjudication was done at a facility that was not one of the study sites conducting the study. Slides for adjudication were even ly divided between three (3) adjudication panels each consisting of one (1) Cytotechnologist and three (3) independent Pathologists. Each adjudicatio n pa nel was bli nde d t o the ori ginal revi ew di agn osis for al l slides a nd each independent Pathologist within each panel was also blinded to other adjudicator’s diagnoses for all slides. Adjudication consensus agreement was obtained for each slide reviewed. Consensus agreement was achieved when at least two (2) of the three (3) Pathologists from a panel rendered an identical diagnosis. In cases where consensus agreement was not achieved the panel members were brought together at a multi-head microscope to review the slides together and come to a consensus diagnosis.

In the study, there were 18 Cancer, 92 HSIL, 37 ASC-H, 180 LSI L, 18 AGUS, 122 ASC-US, 770 NILM, and 23 UNSAT specimens. Clinical sensitivity and specificity (e.g., with reference to a histological diagnosis) cannot be measured in this study which relied on cytological examination alone. Instead, laboratory positive and negative diagnoses by both methods, Imager-assisted and manual review, for the specimens with Reference Diagnosis of ASC-US+ (combined ASC-US, AGUS, LSIL, ASC-H, HSIL, and Cancer), LSIL+ (combined LSIL, ASC-H, HSIL, and Cancer), ASC-H+ (combined ASC-H, HSIL, and Cancer) and HSIL+ (combined HSIL and Cancer) were compared.

MAN-03938-001 Rev. 002 page 15 of 23

Clinical Study Results

Tables 17 through 20 present the comparison of Laboratory true positive and negative rates for ASC-US+, LSIL+, ASC-H+, and HSIL+.

Table 17: Laboratory Imager-Assisted Review Results vs. Laboratory Manual Review Results for the Specimens with Reference Diagnosis of ASC-US+

In the study, there were 467 specimens with Reference Diagnosis of ASC-US+ (combined ASC-US, AGUS, LSIL, ASC-H, HSIL, and Cancer) and 770 specimens with Reference Diagnosis of NILM.

In this table, “Positive” means ASC-US+ or UNSAT, and “Negative” means NILM. All percentages are rounded to the nearest 0.1%.

ASC-US+ Positive Percent Agreement Negative Percent Agreement Lab CT/

Pathologist

Combined

Imager-Assisted Manual Difference Imager-Assisted Manual Difference

(95% CI) (95% CI) (95% CI) (95% CI) (95% CI) (95% CI)

93.8% 95.1% -1.3% 84.4% 81.9% 2.5%

(287/306) (291/306) (-4/306) (434/514) (421/514) (13/514)

(90.5% to 96.0%) (92.1% to 97.0%) (-4.2% to 1.5%) (81.0% to 87.3%) (78.3% to 85.0%) (-0.2% to 5.3%)

91.6% 92.3% -0.6% 84.8% 85.2% -0.4%

(428/467) (431/467) (-3/467) (653/770) (656/770) (-3/770)

(88.8% to 93.8%) (89.5% to 94.4%) (-3.3% to 1.9%) (82.1% to 87.2%) (82.5% to 87.5%) (-2.9% to 2.1%)

91.9% 91.4% 0.4% 83.0% 83.4% -0.4%

(429/467) (427/467) (2/467) (639/770) (642/770) (-3/770)

(89.0% to 94.0%) (88.5% to 93.6%) (-2.1% to 3.0%) (80.2% to 85.5%) (80.6% to 85.8%) (-2.9% to 2.1%)

92.3% 92.7% -0.4% 84.0% 83.7% 0.3%

(1144/1240) (1149/1240) (-5/1240) (1726/2054) (1719/2054) (7/2054)

(90.6% to 93.6%) (91.1% to 94.0%) (-1.9% to 1.1%) (82.4% to 85.6%) (82.0% to 85.2%) (-1.1% to 1.8%)

MAN-03938-001 Rev. 002 page 16 of 23

Table 18: Laboratory Imager-Assisted Review Results vs. Laboratory Manual Review Results for the Specimens with Reference Diagnosis of LSIL+

In the study, there were 327 specimens with Reference Diagnosis of LSIL+ (combined LSIL, ASC-H, HSIL, and Cancer) and 910 specimens with Reference Diagnosis of (combined NILM, ASC-US, and AGUS).

In this table, “Positive” means LSIL+ or UNSAT, and “Negative” means NILM or ASC-US/AGUS. All percentages are rounded to the nearest 0.1%.

LSIL+ Lab CT/

Pathologist

Combined

Imager-Assisted Manual Difference Imager-Assisted Manual Difference

(95% CI) (95% CI) (95% CI) (95% CI) (95% CI) (95% CI)

93.9% 90.0% 3.9% 86.1% 85.3% 0.8%

(215/229) (206/229) (9/229) (509/591) (504/591) (5/591)

(90.0% to 96.3%) (85.4% to 93.2%) (-0.5% to 8.5%) (83.1% to 88.7%) (82.2% to 87.9%) (-1.7% to 3.5%)

85.0% 88.1% -3.1% 87.4% 87.7% -0.3%

(278/327) (288/327) (-10/327) (795/910) (798/910) (-3/910)

(80.7% to 88.5%) (84.1% to 91.2%) (-7.0% to 0.8%) (85.0% to 89.4%) (85.4% to 89.7%) (-2.3% to 1.6%)

93.9% 87.5% 6.4% 84.3% 84.6% -0.3%

(307/327) (286/327) (21/327) (767/910) (770/910) (-3/910)

(90.7% to 96.0%) (83.4% to 90.6%) (3.2% to 10.0%) (81.8% to 86.5%) (82.1% to 86.8%) (-2.4% to 1.7%)

90.6% 88.3% 2.3% 85.9% 85.9% 0.0%

(800/883) (780/883) (20/883) (2071/2411) (2072/2411) (-1/2411)

(88.5% to 92.4%) (86.0% to 90.3%) (0.1% to 4.5%) (84.5% to 87.2%) (84.5% to 87.3%) (-1.3% to 1.2%)

Positive Percent Agreement Negative Percent Agreement

MAN-03938-001 Rev. 002 page 17 of 23

Table 19: Laboratory Imager-Assisted Review Results vs. Laboratory Manual Review Results for the Specimens with Reference Diagnosis of ASC-H+

In the study, there were 147 specimens with Reference Diagnosis of ASC-H+ (combined ASC-H, HSIL, and Cancer) and 1,090 specimens with Reference Diagnosis of (combined NILM, ASC-US/AGUS, and LSIL).

In this table, “Positive” means ASC-H+ or UNSAT, and “Negative” means NILM, ASC-US/AGUS, or LSIL. All percentages are rounded to the nearest 0.1%.

ASC-H+ Lab CT/

Pathologist

Combined

Imaged Manual Difference Imaged Manual Difference

(95% CI) (95% CI) (95% CI) (95% CI) (95% CI) (95% CI)

93.7% 88.3% 5.4% 86.7% 86.7% 0.0%

(104/111) (98/111) (6/111) (615/709) (615/709) (0/709)

(87.6% to 96.9%) (81.0% to 93.0%) (-0.6% to 12.0%) (84.0% to 89.0%) (84.0% to 89.0%) (-2.2% to 2.2%)

86.4% 86.4% 0.0% 89.4% 89.4% -0.1%

(127/147) (127/147) (0/147) (974/1090) (975/1090) (-1/1090)

(79.9% to 91.0%) (79.9% to 91.0%) (-6.8% to 6.8%) (87.4% to 91.1%) (87.5% to 91.1%) (-1.8% to 1.6%)

95.2% 89.8% 5.4% 88.2% 87.4% 0.7%

(140/147) (132/147) (8/147) (961/1090) (953/1090) (8/1090)

(90.5% to 97.7%) (83.8% to 93.7%) (-0.1% to 11.4%) (86.1% to 90.0%) (85.3% to 89.3%) (-1.0% to 2.5%)

91.6% 88.1% 3.5% 88.3% 88.0% 0.2%

(371/405) (357/405) (14/405) (2550/2889) (2543/2889) (7/2889)

(88.5% to 93.9%) (84.6% to 90.9%) (0.0% to 7.0%) (87.0% to 89.4%) (86.8% to 89.2%) (-0.8% to 1.3%)

Positive Percent Agreement Negative Percent Agreement

MAN-03938-001 Rev. 002 page 18 of 23

HSIL+ Lab CT/

Pathologist

Combined

Table 20: Laboratory Imager-Assisted Review Results vs. Laboratory Manual Review Results for the Specimens with Reference Diagnosis of HSIL+

In the study, there were 110 specimens with Reference Diagnosis of HSIL+ (combined HSIL and Cancer) and 1,127 specimens with Reference Diagnosis of (combined NILM, ASC-US/AGUS, LSIL, and ASC-H).

In this table, “Positive” means HSIL+ or UNSAT, and “Negative” means NILM, ASC-US/AGUS, LSIL, or ASC-H. All percentages are rounded to the nearest 0.1%.

Positive Percent Agreement Negative Percent Agreement

Imaged Manual Difference Imaged Manual Difference

(95% CI) (95% CI) (95% CI) (95% CI) (95% CI) (95% CI)

90.7% 80.2% 10.5% 86.8% 89.1% -2.3%

(78/86) (69/86) (9/86) (637/734) (654/734) (-17/734)

(82.7% to 95.2%) (70.6% to 87.3%) (2.9% to 18.8%) (84.1% to 89.0%) (86.6% to 91.2%) (-4.6% to -0.1%)

80.9% 74.5% 6.4% 92.1% 92.3% -0.2%

(89/110) (82/110) (7/110) (1038/1127) (1040/1127) (-2/1127)

(72.6% to 87.2%) (65.7% to 81.8%) (-2.0% to 14.7%) (90.4% to 93.5%) (90.6% to 93.7%) (-1.7% to 1.4%)

90.9% 82.7% 8.2% 89.0% 89.7% -0.7%

(100/110) (91/110) (9/110) (1003/1127) (1011/1127) (-8/1127)

(84.1% to 95.0%) (74.6% to 88.7%) (0.7% to 16.0%) (87.0% to 90.7%) (87.8% to 91.3%) (-2.4% to 0.9%)

87.3% 79.1% 8.2% 89.6% 90.5% -0.9%

(267/306) (242/306) (25/306) (2678/2988) (2705/2988) (-27/2988)

(83.1% to 90.5%) (74.2% to 83.3%) (3.7% to 12.7%) (88.5% to 90.7%) (89.4% to 91.5%) (-1.9% to 0.1%)

In the study, there were 1.83% (23/1260) ThinPrep 5000 slides with UNSAT results by Adjudication.

MAN-03938-001 Rev. 002 page 19 of 23

ImagerAssisted

Review

Three lab CTs have

read the

same slide

Agreement among Laboratory Cytotechnologists/Pathologists

The following tables indicate the extent to which the laboratory Cytotechnologists/Pathologists at a given site agreed amongst t hemselves on the diagno sis, comparing the Im ager-assisted review to the manual review. Tables are provided for ASC-US+ and ASC-H+. Note that since one site had only two CT/Pathologist pairs, the three-way agreement analysis is available for just two sites, with 840 total specimens.

In Table 21 for ASC-H+, the number of specimens is shown for which various levels of agreement among the CTs occurred. Either all three CTs rated the slide as positive (ASC-H+), two out of three rated it positive, one out of three, or none of them.

Table 21: Laboratory Cytotechnologist/Pathologist Agreement, All Results, ASC-H+

ASC-H+

Three CTs had

ASC-H+

Two CTs had ASC-H+

and one had <ASC-H

One CT had ASC-H+ and two had <ASC-H

Three lab CTs have read the same slide

Three CTs

had

ASC-H+

91 23 8 0 122

12 21 7 8 48

3 12 16 11 42

Manual Review

Two CTs had

ASC-H+

& one had

<ASC-H

One CT had

ASC-H+

& two had

<ASC-H

Three

CTs had

<ASC-H

Totals

Three CTs had

<ASC-H

Totals

ASC-H+

ImagerAssisted

Review

Three lab CTs have

read the

same slide

Three or two CTs had

ASC-H+

Three or two CTs had

<ASC-H

Totals

0 2 22 604 628

106 58 53 623 840

Manual Review

Three lab CTs have read the same slide

Three or two CTs

had ASC-H+

147 23 170

17 653 670

164 676 840

Three or two CTs

had <ASC-H

Totals

MAN-03938-001 Rev. 002 page 20 of 23

The rate of agreement between the Imager-assisted review result an d the m anual revi ew result from the previous table is presented below. PPA is the positive percent agreement, percent of specimens of ASC-H+ diagnosis with Imager-assisted review by a majority of laboratory CT/Pathologists among all specimens of ASC-H+ diagnosis with manual review by a majority of laboratory CT/Pathologists. NPA is the negative percent agreement, percent of specimens of <ASC-H diagnosis with Imager-assisted review by a majority of laboratory CT/Pathologists among all specimens of <ASC-H diagnosis with manual review by a majority of laboratory CT/Pathologists.

Table 22: Rate of CT/Pathologist Agreement, ASC-H+

ASC-H+

PPA NPA

89.0% (147/164) (83.3% to 92.9%)

96.6%

(653/676)

(95.0% to 97.7%)

In Table 23 for ASCUS+, the number of specimens is shown for which various levels of agreement among the CTs occurred. Either all three CTs rated the slide as positive (ASCUS+), two out of three rated it positive, one out of three, or none of them.

Table 23: CT Agreement, All Results, ASCUS+

Manual Review

Two CTs had

ASCUS+ &

one had

<ASCUS

One CT had

ASCUS+ &

two had

<ASCUS

ImagerAssisted

Review

Three lab CTs

have read the

same slide

ASCUS+

Three CTs had

ASCUS+

Two CTs had

ASCUS+ and one had

<ASCUS

One CT had ASCUS+ and two had <ASCUS

Three CTs had

<ASCUS

Three lab CTs have read the same slide

Three CTs

had

ASCUS+

272 22 8 0 302

15 16 6 7 44

7 10 24 38 79

0 5 28 382 415

Three CTs

had

<ASCUS

Totals

ASCUS+

ImagerAssisted

Review

Three lab CTs have

read the

same slide

Three or two CTs had

ASCUS+

Three or two CTs had

<ASCUS

Totals 347 493 840

294 53 66 427 840

Manual Review

Three lab CTs have read the same slide

Three or two CTs

had ASCUS+

325 21 346

472 494

Three or two CTs

had <ASCUS

MAN-03938-001 Rev. 002 page 21 of 23

Totals

The rate of agreement between the Imager-assisted review result an d the m anual revi ew result from the previous table is presented below. PPA is the positive percent agreement, percent of specimens of ASCUS+ diagnosis with Imager-assisted review by a majority of laboratory CT/Pathologists among all specimens of ASCUS+ diagnosis with manual review by a majority of laboratory CT/Pathologists. NPA is the negative percent agreement, percent of specimens of <ASCUS diagnosis with Imager-assisted review by a majority of laboratory CT/Pathologists among all specimens of <ASCUS diagnosis with manual review by a majority of laboratory CT/Pathologists.

Table 24: Rate of CT Agreement, ASCUS+

ASCUS+

PPA NPA

93.7% (325/347) (90.6% to 95.8%)

95.7% (472/493) (93.6% to 97.2%)

H. Clinical Investigation Conclusions

 For all sites combined for ASCUS+, the improvement in sensitivity of the Imager Review

method over the Manual Review method is statistically significant. This increase is 6.4% with a 95% confidence interval of 2.6% to 10.0% for all sites combined. The differences in sensitivity varied among the sites from –2.8% to +14.4%. For LSIL+ and HSIL+ the sensitivity of the Imager Review method is equivalent to the Manual Review method.

 For all sites combined for HSIL+, the improvement in specificity of the Imager Review

method over the Manual Review method is statistically significant. This increase is 0.2% with a 95% confidence interval of 0.06% to 0.4% for all sites combined. The differences in specificity varied among the sites from –0.1% to +0.7%. For ASCUS+ and LSIL+ the specificity of the Imager Review method is equivalent to the Manual Review method.

 Specimen adequacy can be determined using the method described in Bethesda System

2001 or by having the Cytotechnologist count the cells in the 22 fields of view presented by the Imager.

 The workload limit for the ThinPrep Imaging System has be en est a bl is hed at 200 slides in

no less than an 8-hour workday. This workload limit of 200 slides includes the time spent for manual review of slides that is not to exceed 100 slides in an 8 hour workday.

For these clinical sites and these study populations, the data from the clinical trial and clinical support studies demonstrate that the use of the ThinPrep Imaging System to assist during primary screening of ThinPrep Pap Test slides for all cytologic interpretations, as defined by the Bethesda System, is safe and effective for the detection of cervical abnormalities.

Performance may vary from site to site as a result of differences in patient populations and reading practices. As a result each laboratory using t his device s houl d employ qualit y assurance a nd contr ol systems to ensure proper use and selection of appropriate workload limits.

MAN-03938-001 Rev. 002 page 22 of 23

I. Bibliography

1. Solomon D., Davey D, Kurman R, Moriarty A, O’Connor D, Prey M, Raab S, Sherman M, Wilbur D, Wright T, Young N, for the Forum Group Members and the 2001 Bethesda Workshop. The 2001 Bethesda System Terminology for Reporting Results of Cervical Cancer. JAMA. 2002;287:2114-2119.

2. Kurman RJ, Solomon D. The Bethesda System for Reporting Cervical/Vagin al Cytologic Diagnoses. Springer-Verlag 1994.

3. Schafer, J.L. Multiple imputation: a primer. Statistical Methods in Medical Research, 1999, 8:3-

15.

4. Nationa l Cancer Institute. SEER Cancer Statistics Review 1973-1998. Available at:

http://www.seer.cancer.gov. Accessed February 2002.

Hologic, Inc. 250 Campus Drive Marlborough, MA 01752 USA 1-800- 442-9892 www. hologic.com

MAN-03938-001 Rev. 002 page 23 of 23

AW-12515-001 Rev. 001

Table of Contents

Chapter One

INTRODUCTION

SECTION A:

SECTION B:

SECTION C:

SECTION D:

SECTION E:

SECTION F:

SECTION G:

Chapter Two

INSTALLATION

SECTION A:

SECTION B:

SECTION C:

SECTION D:

SECTION E:

SECTION F:

SECTION G:

Overview and Function of the Review Scope 1.1

The ThinPrep® Imaging System Process 1.4

Specimen Preparation and Processing 1.6

Review Scope Technical Specifications 1.6

Internal Quality Control 1.13

Review Scope Hazards 1.13

Disposal 1.18

General 2.1

Action Upon Delivery 2.1

Preparation Prior to Installation 2.1

Moving the Review Scope 2.2

Connecting Review Scope Components 2.3

Power On the Review Scope 2.7

Storage and Handling - Post Installation 2.10

Chapter Three

OPERATION OF THE REVIEW SCOPE

SECTION A:

SECTION B:

SECTION C:

SECTION D:

SECTION E:

SECTION F:

Overview 3.1

Materials Required Prior to Operation 3.5

Auto Review 3.6

Subsequent Review 3.16

Manual Slide Review 3.18

Shutting Down the Review Scope 3.24

Review Scope Operator’s Manual

Chapter Four

OPERATION OF THE SOFTWARE MENU

SECTION A:

SECTION B:

SECTION C:

SECTION D:

SECTION E:

SECTION F:

SECTION G:

Introduction 4.1

Menu Option 1 Login/Logout 4.3

Menu Option 2 Joystick Calibration 4.4

Menu Option 3 Setup Marker 4.6

Menu Option 4 Preferences 4.13

Menu Option 5 Open Error Log 4.27

Menu Option 6 Usage Count 4.28

ThinPrep Review Scope Preferences Worksheet

Chapter Five

REVIEW SCOPE MAINTENANCE

SECTION A:

SECTION B:

SECTION C:

SECTION D:

SECTION E:

Daily 5.1

General Cleaning 5.1

Replacing the Illuminator Light Bulb 5.2

Replacing the Fuses 5.5

Koehler Alignment 5.8

Chapter Six

TROUBLESHOOTING

SECTION A:

SECTION B:

SECTION C:

SECTION D:

Chapter Seven

DEFINITIONS AND ABBREVIATIONS 7.1

Chapter Eight

SERVICE INFORMATION 8.1

Chapter Nine

ORDERING INFORMATION 9.1

INDEX

Review Scope Operator’s Manual

Operation Errors 6.1

User-Correctable Errors 6.4

Recoverable System Errors 6.13

Miscellaneous 6.13

1. Introduction

INTRODUCTION

SECTION

Chapter One

Introduction

OVERVIEW AND FUNCTION OF THE REVIEW SCOPE

The Review Scope is an automated microscope to be used by a cytotechnologist (CT) to screen ThinPrep® Pap Test slides that have been imaged by a ThinPrep Image Processor. The microscope uses stan-

dard microscope optics enhanced with automated features that facilitate review of the slide. The CT views the slide and by means of automatic stage movement, is presented with fields of view containing objects of interest identified by the Imaging System. A motorized nosepiece allows the CT to change magnification via a pod device, without interrupting visual observation of the slide. An automated slide marking system allows the CT to mark objects for further review by a pathologist. The Review Scope is networked to the imaging system and slide data is retrieved from and later updated and returned to a slide database maintained by the imaging system.

Review Scope Operator’s Manual

1.1

INTRODUCTION

1.2

Review Scope Operator’s Manual

Figure 1-1 Review Scope

ThinPrep® Imaging System: Laboratory Flow

INTRODUCTION

Figure 1-2 Lab Flow

Review Scope Operator’s Manual

1.3

INTRODUCTION

SECTION

THE THINPREP® IMAGING SYSTEM PROCESS

Slides that have been prepared for screening are loaded into cassettes which are placed into the Imaging Station. The operator uses a PC keyboard, mouse and monitor to interact with the instru ment via a graphic, menu driven interface.

A slide ID reader scans the slide accession ID and then the Imaging Station scans the entire ThinPrep cell spot. The system identifies objects of interest found on the slide, based on integrated optical den sity. (Refer to Figure 1-3, ThinPrep Imaging Process.) The coordinates of 22 of those objects are recorded and the slide is returned to its cassette. Following processing of each cassette of slides, the numeric slide ID and associated data record are sent to the Server.

The Server acts as the central data manager for the ThinPrep® Imaging System. As slides are imaged by the Image Processor and reviewed at the Review Scope, the Server stores, retrieves and transmits information based on the slide ID.

The Cytotechnologist (CT) reviews slides at the Review Scope (RS). The RS consists of elements of a standard microscope, augmented with automated capabilities for viewing and marking the micro scope slides. The RS contains an optical scanner which reads the slide ID when a slide is loaded on the stage. When a valid slide accession ID has been identified at the RS, the Server sends the object of interest coordinates for that ID and the CT is presented with the 22 fields of view determined for that slide. It is required that the CT review each of these fields of view before completing a slide review.

As each field of view is being reviewed, the CT has the option to electronically mark the contents of the field for subsequent physical marking at completion of the slide review. The CT always has the option to control the position of the stage/slide manually, which provides complete freedom to move any portion of the ThinPrep cell spot into the field of view for examination.

Note:

Before completing the review, the CT may revisit any locations and mark or unmark fields of view, as desired. At the conclusion of electronically marking the slide, physical marks are applied at those locations with a semi-permanent translucent marker. A “slide reviewed” mark is placed on the slide at the end of the review, whether or not any physical marks were placed.

The object of interest is typically placed in the center of the field of view, however the CT screen the entire field of each of the 22 fields of view presented.

must

1.4

Review Scope Operator’s Manual

INTRODUCTION

Figure 1-3 ThinPrep® Imaging Process

Review Scope Operator’s Manual

1.5

INTRODUCTION

SECTION

SPECIMEN PREPARATION AND PROCESSING

Specimens for the ThinPrep® Pap Test cytology slide are collected by a clinician, then immersed and

rinsed in a PreservCyt ratory equipped with a ThinPrep Processor. The samples are processed on ThinPrep Imaging System slides. After being processed, the slides are stained with ThinPrep Stain.

Please refer to the Operator’s Manuals of these instruments and stain for more information regarding preparation and processing of ThinPrep slides.

Specimen Handling and Stability

The ThinPrep slides are stored, transported and handled the same as conventional cytology slides. Please refer to your laboratory guidelines for specimen handling.

Solution sample vial. The sample is then capped, labeled, and sent to a labo-

REVIEW SCOPE TECHNICAL SPECIFICATIONS

Overview of Components

Refer to Figure 1-4 to Figure 1-8 for information regarding components and specifications.

1.6

Review Scope Operator’s Manual

INTRODUCTION

Motorized Object Marker Mechanism

Motorized Nosepiece

Binoculars

Object Marker Pen

Network Connection (on

rear of Scope)

Model/Rating Label (on

rear of Scope)

Power Cord;

On/Off Switch

(on rear of Scope)

Coarse Focus

Fine Focus (on both

sides of Scope)

10X/40X Objectives Motorized Nosepiece

Motorized Stage

Condenser (Aperture) Lens (underneath stage)

Collector (Field) Lens

Illuminator Assembly (underneath)

Lamp On/Off Switch

Lamp Intensity Adjustment

Console

Navigator Pod

White & Green Mark Indicator Intensity Adjustments

(4-Button Pod) or ( 5-Button Pod)

Note: only one pod is used

Focus Knob for Condenser Lens

Note:

Certain models of the ThinPrep Review Scope (model numbers 70669-001, 70669-002, and 70669-003) require a different pen and special setup instructions. See "MENU OPTION 3 SETUP MARKER" on page 4.6.

Figure 1-4 Review Scope Components

Review Scope Operator’s Manual

1.7

Dimensions

12

(304 mm)

Wide

21

(533 mm)

High

23

(584 mm)

Deep

Approximate Weight: 38 lbs (17.24 kg)

4

(101 mm)

Rear

27

(610 mm)

Deep

32

(813 mm)

Wide

12

(305 mm)

Wide

INTRODUCTION

Figure 1-5 Review Scope Dimensions

Figure 1-6 Recommended Clearances

1.8

Review Scope Operator’s Manual

INTRODUCTION

5.5

(140 mm)

7

(178 mm)

3

(76 mm)

1 (25 mm)

4

(102 mm)

3

(76 mm)

4.75

(121 mm)

1.5

(38 mm)

Console (Display and Keypad)

Approximate Weight:

3.3 oz (95 g)

Approximate Weight:

13.4 oz (380 g)

4-Button Pod

5-Button Pod

Note: (only one pod is used)

Approximate Weight:

4.3 oz (122g)

Figure 1-7 Console and Navigator Pod

Review Scope Operator’s Manual

1.9

INTRODUCTION

14-digit numeric accession ID (OCR label format shown)

Fiducial Mark

Frosted portion of the slide

Cell spot - contains patient

sample cells

Fiducial Mark

ThinPrep® Microscope Slide for Use with the Imaging System

The ThinPrep microscope slide is used by the ThinPrep Processor in preparing the patient slide. The slide utilizes fiducial marks, or fixed reference points, which are permanently printed features on the slide that are used to register the slide position on the stage. A coordinate system is based on the fidu cial marks, for locating objects of interest on the cell spot.

Slide Labeling Formats

The formats that the optical scanner on the Review Scope can read for the accession ID on the slide label are configured on the Imaging System server. Refer to the Image Processor Operator’s Manual for specifications for slide label formats.

Environmental

Operating Temperature Range:

16°C to 32°C

Non-Operating Temperature Range:

-28°C to 50°C

Operating Humidity Range:

20 to 80% relative humidity, non-condensing

Non-Operating Humidity Range:

15 to 95% relative humidity, non-condensing

Pollution Degree II

Figure 1-8 ThinPrep Microscope Slide

(the Review Scope is plugged in and turned on.)

(the Review Scope is plugged in but not turned on)

, in accordance with IEC 60664.

1.10

Review Scope Operator’s Manual

INTRODUCTION

Category II

ronment.

Altitude:

Atmospheric Pressure:

. The ThinPrep Review Scope is for indoor use only in an office or a clean laboratory envi-

0 meters (sea level) to 2000 meters

Power

Voltage:

100-120 / 200-240~ (Volts alternating current, no selection required)

Mains supply voltage not to exceed ± 10% of the nominal voltage

Frequency:

50-60 Hz

Power:

2A maximum

Heat Generated:

Approximately 600 BTU/HR (176W)

Fusing:

1100 millibar to 500 millibar

Two T2.5A, 250V, 5 x 20 mm, glass, time delay, low break capacity

F1 - 2.5A fused AC to 12V supply, located on Illumination Control Board

Protective Temperature Coefficient Devices

This unit contains protective temperature coefficient (PTC) devices intended for protection against occasional overcurrent or overtemperature fault conditions. These devices automatically reset after the overcurrent or overtemperature condition has been removed.

The PTCs locations and functions are as follows:

System Hardware Electromechanical Processor (SHEMP) F1 - 1A PTC - 5V sensor power to sensor ports J4 and J5 F2 - 1A PTC - 5V sensor power to sensor ports J2 and J3 F3 - 1A PTC - Isolated 5V for the CAN BUS F4 - 500ma PTC - 24V line to protect against motor or drive failure

Servo Interface Module (SERVIM) R21 - 1.85A PTC - 24V line to protect FETS and motors

Review Scope Operator’s Manual

1.11

INTRODUCTION

Dimensions and Weight (Approximate)

Review Scope: 21” (533mm) H x 12” (304mm) W x 23” (584mm) D 38 lbs (17 kg)

Console:

3.5” (89mm) H x 5.5” (140mm) W x 7” (178mm) D

13.4 oz (380 g)

Navigator Pod:

4-button pod: 1” (25mm) H x 4” (102mm) W x 3” (76mm) D

3.3 oz (95 g)

5-button pod:

4.75” (121mm) H x 3” (76mm) W x 1.5” (38mm) D

4.3 oz (122 g)

Review Scope Standards

The ThinPrep® Review Scope Laboratory (NRTL) to comply with current Safety, Electro-Magnetic Interference (EMI) and Elec tro-Magnetic Compatibility (EMC) standards. Refer to the product label, located on the rear of the instrument, to see the safety certification markings.

Do not use this device in close proximity to sources of strong electromagnetic radiation (e.g., unshielded intentional RF sources), as these may interfere with proper operation.

has been tested and certified by a U.S. nationally recognized testing

This product is in vitro diagnostic (IVD) medical equipment.

This product contains a device classified per EN 60825-1: 1994, Issue 2, June 1997 as a Class 1 LED Product.

1.12

Review Scope Operator’s Manual

INTRODUCTION

SECTION

INTERNAL QUALITY CONTROL

Power On Self Test

When the Review Scope is powered on (refer to Power On the Review Scope page 2.7), the instrument goes through a self-diagnostic test. Electrical, mechanical and software systems are tested to confirm each functions properly. Network communication is tested at the time the user Logs In for an Auto Review session. The operator is alerted to any malfunction via a message on the console dis play.

If the system does not function, or there are persistent errors, contact Hologic Technical Support. (Refer to

Service Information, Chapter 8.)

REVIEW SCOPE HAZARDS

The Review Scope is intended to be operated in the manner specified in this manual. Be sure to review and understand the information listed below in order to avoid harm to operators and/or damage to the instrument.

If this equipment is used in a manner not specified by the manufacturer, then the protection provided by the equipment may be impaired.

Warnings, Cautions and Notes

The terms WARNING, CAUTION and Note have specific meanings in this manual.

• A

WARNING

injury or death.

• A

CAUTION

inaccurate data or invalidate a procedure, although personal injury is unlikely.

• A

Note

provides useful information within the context of the instructions being provided.

advises against certain actions or situations that could result in personal

advises against actions or situations that could damage equipment, produce

Review Scope Operator’s Manual

1.13

INTRODUCTION

Symbols Used on the Instrument

The following is an explanation of the symbols that may appear on your product:

Symbol Title Description Standard information

Caution Indicates the need for th e user

to consult the instructions for use for important cautionary information such as warnings and precautions that cannot, for a variety of reasons, be presented on the medical device itself.

In vitro diagnostic medical device

Authorized Representative in the European Community

Serial number Indicates the manufacturer’s

Indicates a medical device that is intended to used as an in vitro diagnostic medical device

Indicates the Authorized Representative in the European Community

serial number so that a specific medical device can be identified

ISO 15223-1 Medical devices—Symbols to be used with medical device labeling and information to be supplied, Section 5.4.4

ISO 15223-1 Medical devices—Symbols to be used with medical device labeling and information to be supplied, Section 5.5.1

ISO 15223-1 Medical devices—Symbols to be used with medical device labeling and information to be supplied, Section 5.1.2

ISO 15223-1 Medical devices—Symbols to be used with medical device labeling and information to be supplied, Section 5.1.7

Catalogue Number

Manufacturer Indicates the medical device

Fuse To identify fuse boxes or their

1.14

Review Scope Operator’s Manual

Indicates the manufacturer's catalogue number so that the medical device can be identified

manufacturer, as defined in the EU Directives 90/385/EEC, 93/ 42/EEC and 98/79/EC

location.

ISO 15223-1 Medical devices—Symbols to be used with medical device labeling and information to be supplied, Section 5.1.6

ISO 15223-1 Medical devices—Symbols to be used with medical device labeling and information to be supplied, Section 5.1.1

IEC 60417 Graphical symbols for use on equipment, symbol 5016

INTRODUCTION

Symbol Title Description Standard information

Caution, hot surface To indicate that the marked

item can be hot and should not be touched without taking care

Caution, risk of electric shock

Protective earth; protective ground

Figure 1-9 Symbols used on the instrument

The Review Scope has symbols placed on it specifically to advise the operator to refer to the Operator’s Manual. (Refer to Figure 1-10.) Be sure to review and understand the warnings listed below in order to avoid damage to the instrument and any harm to operators. One or more of the warnings may be pertinent to the area marked.

To identify equipment that has risk of electric shock

To identify any terminal which is intended for connection to an external conductor for protection against electric shock in case of a fault, or the terminal of a protective earth (ground) electrode

IEC 60417 Graphical symbols for use on equipment, symbol 5041

IEC 60417 Graphical symbols for use on equipment, symbol 5042

IEC 60417 Graphical symbols for use on equipment, symbol 5019

The instrument model/rating label and the serial number label are also located on the Review Scope.

Review Scope Operator’s Manual

1.15

INTRODUCTION

Motorized Stage

Crushing/Pinch Point Moving Parts Glass

Rear Of Scope

External Connections Fusing Grounded Outlet

Bottom, Interior of Scope

Hot Surfaces (the lightbulb itself may be hot)

Bottom, Exterior of Scope

Operator Access

Model/Rating Label

Serial Number Label

Review Scope

ThinPrep Imaging System

CYTYC

corporation

85 Swanson Road Boxborough, MA USA 01719

90-264V~ 4A 47-63 Hz

2 X T6.3AL 250V 5x20 mm

Part Number Label

WEEE Label

Location of Labels on the Instrument

1.16

Review Scope Operator’s Manual

Figure 1-10 Label Locations

INTRODUCTION

Warnings Used in this Manual:

WARNING

Service Installation Only

This instrument is to be installed by trained Hologic® personnel only.

WARNING

Instrument Fusing

For continued protection against fire, replace only with fuses of the specified type and current rating. Refer to the Refer to Ordering Information for fuse specification and ordering.

Review Scope Maintenance chapter for instructions on replacing user accessible fuses.

WARNING

Moving Parts

The instrument contains moving parts. Keep hands, hair, loose clothing, jewelry, etc., clear.

WARNING

Grounded Outlet

To ensure safe operation of the instrument, use a three-wire grounded outlet.

WARNING

Glass

The instrument uses microscope slides, which have sharp edges. In addition, the slides may be broken in their storage packaging or on the instrument. Use caution when handling glass slides and when cleaning the instrument.

Review Scope Operator’s Manual

1.17

INTRODUCTION

SECTION

WARNING

Hot Surfaces

The microscope contains hot surfaces. Use extreme caution when handling items near these surfaces. Allow hot surfaces to cool before handling. The light bulb contained in the collector housing may be hot.

DISPOSAL

Disposal of Consumables

Marking Pens. No special instructions; used marking pens may be disposed of in your laboratory refuse.

Halogen light bulbs. No special instructions; used light bulbs may be disposed of in your laboratory refuse.

Instrument fuses. No special instructions; used fuses may be disposed of in your laboratory refuse.

Disposal of the Device

Please contact Hologic Service (refer to Service Information, Chapter 8).

Do not dispose in municipal waste.

Please contact Hologic Technical Support.

Hologic, Inc. 250 Campus Drive Marlborough, MA 01752 USA Tel: 1-800-442-9892

1-508-263-2900 Fax: 1-508-229-2795 Web: www.hologic.com

1.18

Review Scope Operator’s Manual

2. Installation

Chapter Two

SECTION

Installation

INSTALLATION

WARNING:

Service Installation Only

GENERAL

The ThinPrep® Review Scope must be installed by Hologic Service Personnel. When installation is complete, Hologic personnel trains the operator(s), using the Operator’s Manual as the training guide.

ACTION UPON DELIVERY

Remove and read the

Inspect the packing cartons for damage. Report any damage immediately to the shipper and/or Hologic Technical Support as soon as possible. (Refer to

Leave the instrument in the packing cartons for Hologic Service installation.

Store the instrument in a suitable environment until installation (cool, dry, vibration-free area).

Operating Instructions Prior to Installation

Service Information, Chapter 8.)

sheet attached to the packing carton.

PREPARATION PRIOR TO INSTALLATION

Pre-Installation Site Assessment

A pre-installation site assessment is performed by Hologic Service Personnel. Be sure to have prepared any and all site configuration requirements as instructed by the Service personnel.

Location And Configuration

Review Scopes connected to the Server may be local or up to 200 meters (656 feet) away. Room for the console and Navigator Pod that accompany each review scope should be accommodated, as well as a comfortable amount of desk space for placing slide cassettes, flats or other slide containers. (Refer to Figure 2-1.)

Review Scope Operator’s Manual

2.1

INSTALLATION

SECTION

CAUTION:

over, or disconnecting cabling, do not place cabling near foot traffic.

The Review Scope is sensitive to vibrations. It should be placed on a flat, sturdy surface away from any vibrating equipment.

Route connections carefully to avoid pinching the cables. To avoid tripping

Figure 2-1 A Typical Review Scope

MOVING THE REVIEW SCOPE

The Review Scope is a precision instrument and should be handled with care. If the microscope must be moved, it should be grasped and lifted by the frame housing. (Refer to instrument by the motorized stage will cause damage to the microscope and may render it inoperable.

If the Review Scope is to be shipped to a new location, please contact Hologic Technical Support. (Refer to

CAUTION:

Do not rest the stage against your body, as this may misalign the stage.

2.2

Service Information, Chapter 8.)

Do not lift or handle the Review Scope by the stage.

Review Scope Operator’s Manual

Figure 2-2.) Lifting the

INSTALLATION

SECTION

Figure 2-2 Moving the Review Scope

CONNECTING REVIEW SCOPE COMPONENTS

The Review Scope provides electrical and software interface for the display console and the control pod. The microscope is connected to the Server via an ethernet cable to receive and transmit slide data, user preferences and other data for report generation.

The power cord (refer to Figure 2-3) provides electrical power to the Review Scope. It must be plugged into a 3-prong grounded outlet. Disconnection from the power supply source is by removal of the power cord.

• The network connection (refer to Figure 2-3) connects the Review Scope to the hub, enabling

communication to the Server located in the Image Processor Controller.

• The console connection is used to interface the console and pod to the Review Scope. The

operator interfaces with the Review Scope via these peripheral devices.

• The service port (refer to Figure 2-3) is to be used only by trained Hologic personnel for ser-

vice and diagnostic purposes.

Review Scope Operator’s Manual

2.3

INSTALLATION

Network connection

Interconnection to RS Console

(Bottom - Service Port for Hologic use only)

Fusing

On Off

Power Cord

Console Contrast Adjustment Knob

(Turn the knob to adjust the contrast of the

console display.)

Interconnection Cable to Navigator Pod

Cable to Review Scope

Console and Navigator Pod

Connect the console unit to the Review Scope by plugging the end of the serial cable into the middle right port on the rear of the microscope. Plug the other end of the cable into the rear of the console.

The console and pod may be placed on either side of the microscope, depending on user preference. The connection cord between them is short, so they must be located together.

The network connection cable from the Server snaps into an available port on the hub or switch. Another cable goes from the hub to the Review Scope, snapping into the connection jack at the top port on the rear of the Scope. (Refer to

CAUTION:

Review Scope.

2.4

Review Scope Operator’s Manual

Only the optional accessories listed in Table 9.2 may be used with the

Figure 2-3 Review Scope, Rear

Figure 2-4 Console, Rear

Figure 2-3.)

INSTALLATION

Eyepieces

Binocular Head

The Review Scope is supplied with a standard, tilting binocular head. (Refer to Figure 2-5.)

Hologic has evaluated the use of an optional riser and an optional telescoping binocular head with the Review Scope. The Hologic Technical Support for more information on the installation of these items.

specific riser and head that may be used are listed in Table 9.1. Contact

CAUTION:

tute eyepieces or lenses.

Eyepieces

The 10X eyepieces slide into their mounting holes in the binoculars. (Refer to Figure 2-5.)

Objectives

The 10X and 40X objective lenses are mounted in the motorized nosepiece on the microscope at the factory.

If an objective must be replaced, an optical alignment is required. Please contact Hologic Technical Support.

Only use Hologic supplied eyepieces and objective lenses. DO NOT substi-

Figure 2-5 Binocular Head With Eyepieces

Review Scope Operator’s Manual

2.5

INSTALLATION

Marking Pen

CAUTION:

Marker function via the software menu.

Certain models of the ThinPrep Review Scope (model numbers 70669-001, 70669-002, and 70669-003) require a different pen and special setup instructions.

The marking pen for some models of the ThinPrep Review Scope is a Sharpie® Ultra Fine Point marking pen. Only use this specified marker for ThinPrep Review Scope model numbers 70575-001, 70575-003, 71062-001, and 71062-002. (Refer to

The marking pen should ONLY be loaded by performing the Calibrate

Figure 2-6.)

Figure 2-6 Sharpie® Marking Pen

The marking pen for the other models of the ThinPrep Review Scope is a Pilot Extra Fine Point marking pen. Only use this specified marker for ThinPrep Review Scope model numbers 70669-001, 70669-002, and 70669-003. (Refer to

The marking pen must be present for physical marking of the slide at the conclusion of a review. Loading the marking pen should Scope software menu. (Refer to Marker Calibration on

Focus Knob Covers

Rubber knob covers for the fine focus knobs are available. They are placed over the focus knob and remain in place via a friction fit. (Refer to them.

Figure 2-7.)

Figure 2-7 Pilot Marking Pen

only

be done by executing “Calibrate Marker” from the Review

page 4.8.)

Figure 2-8.) Contact Hologic Technical Support to request

2.6

Review Scope Operator’s Manual

Figure 2-8 Focus Knob Covers

SECTION

INSTALLATION

POWER ON THE REVIEW SCOPE

The Review Scope power On/Off switch is located at the rear of the microscope. Confirm that it is in the Off position and plug the receptacle end of the power cord into the socket. Plug the other end of the power cord into a wall outlet. To ensure safe operation of the microscope, a three wire grounded outlet must be used. (Refer to

WARNING:

Instrument Fusing Do not power on or operate if equipment has been damaged.

To ensure network communication necessary to operate the automated Review Scope for auto review, the server must be powered on and initialized. The Review Scope may be turned on at any time. Entering a valid Login ID will make a network connection if the server is available.

Power on the Review Scope by pressing the rocker switch on the rear of the scope to On. An audible beep will be heard as the unit powers up. It takes less than a minute for the microscope to become ready for use.

Note:

Disconnection from power supply source is by removal of the power cord.

Grounded Outlet

Figure 2-9.)

Review Scope Operator’s Manual

2.7

INSTALLATION

On Off

Power On LED

Soft keys

(software definable) will implement user selections or actions, associated with the labels on the display directly above the key. Soft key functions and availability will change depending on the current software operational state or mode.

Cancel

key will abort the current operation. Use the Cancel key to back out of submenus or to terminate the slide review.

SOFT KEYS

CANCEL KEY

Figure 2-9 Power Entry Module and On/Off Switch

Allow the microscope to initialize. The instrument is ready for operation when the display on the console shows

Enter Login ID

[Offline]. (Refer to Figure 2-10.)

Figure 2-10 Console Keypad and Display

The Navigator Pod connects to the Review Scope, through the console. The pod is ready for use as soon as

Objective

2.8

Load Slide

Review Scope Operator’s Manual

is displayed on the console.

Figure 2-11 Pod (Default Button Configuration)

used to advance through functions used to pause /resume stage motion during scan used to adjust user preference settings

used to return to fields of view during review used to adjust user preference settings

used to toggle between 10x and 40x magnification

INSTALLATION

OBJECTIVE (10X / 40X) both sides

MARK

JOYSTICK

OBJECTIVE (10X / 40X)

MARK

JOYSTICK

4-BUTTON POD

5-BUTTON POD

Note: Only one pod is used.

Mark

Joystick

Note:

At the control panel on right side of the microscope, turn the lamp power rocker switch to the “on” position. Adjust the illumination to the desired intensity by turning the lamp intensity adjustment dial.

The white and green mark indicator intensities may be set individually by turning their respective adjustment knobs. (Refer to

Koehler illumination may be adjusted using the condenser and collector assemblies. Instructions for making this adjustment may be found in the Koehler Alignment section on

The Navigator Pod button functions are illustrated showing the default configuration. The Next, Previous, Objective and Mark functions can be assigned by the user. Refer to Button Setup.

used to electronically mark or unmark cells for dotting by the marking pen

used for directional and velocity control of the motorized stage during slide review used to increase or decrease stage speed during autoscan

page 4.24,

Figure 2-12.)

page 5.8.

Review Scope Operator’s Manual

2.9

INSTALLATION

Lamp On/Off

Lamp Intensity Adjustment

White & Green Mark Indicator Intensity Adjustments

Focus Knob (on left & right sides, both)

Fine Focus Coarse Focus

Condenser (Aperture) Adjustment Thumbscrews

Condenser (Aperture) Focus Knob

SECTION

The Review Scope may be stored in the location where it was installed. When it is not in use, the power should be turned off. Cover the instrument with the microscope dust cover.

Figure 2-12 Illumination Control Panel

STORAGE AND HANDLING - POST INSTALLATION

2.10

Review Scope Operator’s Manual

3. Operation

OPERATION OF THE REVIEW SCOPE

SECTION

Chapter Three

Operation of the Review Scope

OVERVIEW

ThinPrep® Pap Test cervical cytology sample slides processed by the ThinPrep Imaging System are reviewed at the Review Scope (RS). Slide review by a cytotechnologist is assisted by automated fea tures. (Refer to Figure 3-1 for typical slide review process.)

Auto Review

In this manual, Auto Review refers to a slide review in which the RS

• scans the ID number from the slide

• communicates with the server for appropriate slide data record

• makes use of the Autolocate function (where the 22 fields of view identified by the Image Pro-

cessor are presented to the cytotechnologist, CT)

• makes use of the Autoscan function, as required or desired

• uploads slide data record to the server at conclusion of slide review

Subsequent Review

A slide that has undergone Auto Review may be reviewed again, making use of the Autolocate, review and Autoscan functions. Further marks may be added (to a maximum of 30 marks on a slide), but no previous marks may be removed. The slide data record will be revised at the Server at the con clusion of the review.

Note:

Slides previously screened either via auto review or manually may always be examined again in manual mode.

Review Scope Operator’s Manual

3.1

OPERATION OF THE REVIEW SCOPE

Manual Review

Manual Review refers to a slide review in which

• patient slide data is not retrieved from or communicated to the server

• a scan of the entire cell spot is conducted by the operator initiating each movement of the

stage

• marks may be made (up to 30), but no record is stored on the server

(Refer to Figure 3-1 for a graphical representation of the typical slide review process.)

Important Operational Notes

CAUTION

Moving the Review Scope.)

Calibrate the 4-button pod Joystick and the Object Marker once a day, in that order. (Refer to page 4.4 and page 4.6, respectively.)

: Never lift or handle the Review Scope by the stage. (Refer to Figure 2-2‚

Calibrate the 5-button pod joystick upon installation of the pod, or if the pod has been removed and then reinstalled on a Review Scope. (Refer to

Load the slide properly, seated fully against the back and left guides, to ensure a successful slide ID scan and accurate positioning of Object of Interest coordinates sent from the Server. (Refer to 3-2.)

Always examine the

entire

Field of View. Mark if you see any suspect object and then do Autoscan.

page 4.4.)

Figure

3.2

Review Scope Operator’s Manual

OPERATION OF THE REVIEW SCOPE

Daily Cytotechnologist Screening Rates

Laboratorians should use the following method when calculating workload:

• All slides with Fields of View (FOV) only review count as 0.5 or ½ slide

• All slides with full manual review (FMR) using the Autoscan feature count as 1 slide (as man-

dated by CLIA’88 for manual screening)

• Then, slides with

• Use these values to count workload, not exceeding the CLIA maximum limit of 100 slides in

no less than an 8-hour day.

•

Note:

ALL laboratories should have a clear standard operation procedure for documentation

of their method of workload counting and for establishing workload limits.

• It is the responsibility of the Technical Supervisor to evaluate and set workload limits for indi-

vidual cytotechnologists based on laboratory clinical performance. According to CLIA ‘88, these workload limits should be reassessed every six months.

For less than an 8-hour workday, the following formula must be applied to determine the maximum number of slides to be reviewed during that workday:

The ThinPrep Imaging System limit of 100 slides in an 8-hour workday includes the following:

• Screening 22 Fields of View

both

FOV and FMR count as 1.5 or 1½ slides

FMR = 1 slide

FOV = 0.5 slide

FMR + FOV = 1.5 slides

Upper Limit = 100 slides

Number of hours examining slides X 100

• Full manual slide review using the Autoscan feature

• Review clinical history

• Record results and triage appropriately

The manual workload limit does not supersede the CLIA requirement of 100 slides in no less than an 8-hour day. Manual review includes the following types of slides:

• Slides reviewed on the ThinPrep Imaging System using the Autoscan

feature

• Slides reviewed without the ThinPrep Imaging System

• Non–gynecologic slides.

When conducting manual review, refer to the CLIA requirements for calculating workload limits.

Review Scope Operator’s Manual

3.3

Power On

User Login

Load Slide

Autolocate

Review Marked Fields

Autoscan

Mark Slide

Check

Registration

Unload Slide

Manual Scan

Review Marked Fields

Mark Slide

User LogOut

Power Off

(Optional)

Check

Registration

Online

Offline

(Optional)

(Manual Review Mode)

(Auto Review Mode)

Unload Slide

(if negative)

Verify Marks

Calibrate

Marker (Daily)

Calibrate

Joystick (Daily)

Autoscan

Overlap (choose)

Mark Indicator

(on/off)

(4-button pod)

OPERATION OF THE REVIEW SCOPE

3.4

Review Scope Operator’s Manual

Figure 3-1 Typical Slide Review Process

OPERATION OF THE REVIEW SCOPE

SECTION

MATERIALS REQUIRED PRIOR TO OPERATION

ThinPrep® Pap Test slides imaged by the Image Processor are necessary to begin slide review.

A Sharpie® Ultra Fine Point marking pen or a Pilot Extra Fine point marking pen is used for physically marking the slides, depending on the model of ThinPrep Review Scope you have. If a pen is not already installed, refer to instructions on instrument installation.)

page 4.6 for installing the pen. (A box of pens is provided at

Review Scope Operator’s Manual

3.5

OPERATION OF THE REVIEW SCOPE

SECTION

Enter Login ID

Enter Back

1 Min Overlap 2 Medium Overlap 3 Max Overlap

Test Save

AUTO REVIEW

To login, enter the three-digit User Login ID via the console keypad. Press the Pressing the cancel the Login process.

Each cytotechnologist (CT) must use a unique Login ID. That ID becomes part of the slide data record for each slide screened by the CT. Each Login ID is associated with the CT’s RS options prefer ences. The preferences are downloaded from the Server to any RS the CT logs onto. (Refer to setting preferences on

Back

soft key will perform a backspace/delete function. The

page 4.13.)

Enter

Cancel

soft key to Login.

console key will

Note:

Scan Overlap

An autoscan overlap must be selected. This sets how much the fields of view overlap from row to row during autoscan of the cell spot.

Select the scan overlap:

See your lab administrator for any issues regarding Login ID’s. Also, refer to the ThinPrep Image Processor’s Operator ’s Manual.

• minimum

• medium

• maximum

3.6

Review Scope Operator’s Manual

OPERATION OF THE REVIEW SCOPE

Autolocate

Mark Always ON

2 Mark Turns OFF

Save

Load Slide

Press Next

Manual Menu

The Manual soft key will activate the manual review mode. Refer to page

3.2 for manual review. The Menu soft key will display page

1 of the RS software menu.

AUTO REVIEW (continued)

Mark Indicator

The white mark indicator may be turned off during autolocate, scan or review mode, when fields of interest are presented to the CT.

If it is preferred that the mark indicator always be visible during slide review, select

. Press 1 on the keypad and then press the

If it is preferred that the mark indicator is not visible during slide review, select

Press the operator moves the joystick or presses the Mark button.

Note:

on the keypad and the press the

the green mark indicator is unaffected by the preference setting.

Save

softkey.

Mark Turns OFF

Save

softkey. The white mark indicator will remain off until

Load Slide

WARNING:

Moving Parts

The Load Slide display will appear on the console.

Glass

Mark Always

To proceed with Auto Review, load a slide into the slide holder on the stage by rotating the slide clamp arm open far enough to allow placement of a slide in the holder. The slide should have the ID label face up, to the left. Gently release the arm against the slide.

Make sure the left and back edges of the slide are firmly positioned against the guides of the slide holder. (Refer to

CAUTION:

Confirm it is a clean, properly labeled ThinPrep® Pap Test slide. Check for any damage. Do not load a slide onto the stage upside down.

Figure 3-2‚ Loading a Slide.)

Inspect the slide before loading.

Review Scope Operator’s Manual

3.7

OPERATION OF THE REVIEW SCOPE

Slide Orientation: Frosted Side Up, Label to the Left

Slide Clamp Arm

Align 1st Mark

Press Next

AUTO REVIEW (continued)

Figure 3-2 Loading a Slide

Press the ID has been scanned.

Note:

The stage will move the slide to present the first fiducial mark in the field of view. The display on the console prompts to align the first mark.

Using the joystick on the Navigator Pod, manipulate the view of the slide fiducial mark to align it against the inner edge of the illuminated mark indicator. The left and bottom edges of the fiducial mark should register with the inside of the ‘L’ mark. Bring the fiducial mark into sharp focus. (Refer to

Figure 3-3.)

button on the pod. A flash of red light and a beep will indicate that the slide accession

If the slide reader cannot read the numeric slide ID, you may have to manually enter the slide ID number or manually review the slide. (Refer to page 6.1.)

"Text Messages on the Console Display" on

3.8

Review Scope Operator’s Manual

OPERATION OF THE REVIEW SCOPE

Slide Fiducial Mark

Illuminated Mark Indicator

Good Alignment

Poor Alignment: Fiducial Mark is on top of Illuminated Mark Indicator

Poor Alignment: Fiducial Mark is too far away from Illuminated Mark Indicator

Align 2nd Mark

Press Next/Prev

Align 3rd Mark

Press Next/Prev

AUTO REVIEW (continued)

Figure 3-3 Align the Fiducial Mark and the Mark Indicator

When the fiducial mark is aligned with the mark indicator, press the stage presents the second mark and the display prompts the user to align the second fiducial mark.

Using the joystick control, align the second fiducial mark with the illuminated mark indicator, as necessary. (Pressing the was made.) Press the

The third fiducial mark is presented and the display prompts the user to align the third mark.

Using the joystick control, align the third fiducial mark with the illuminated mark indicator, as necessary. Press the

button will allow re-alignment of the first fiducial mark, in case a mistake

button on the pod when satisfied with the alignment.

button on the pod.

button on the pod. The

Review Scope Operator’s Manual

3.9

OPERATION OF THE REVIEW SCOPE

Autolocate

1 of 22

Press Next

AUTO REVIEW (continued)

Autolocate - Viewing the Slide

The stage moves to present the first field of view to the operator.

Note:

Focus as needed using the focus knobs on either side of the Review Scope.

CAUTION:

Visually scan the entire field of view

the field of view, yet the entire field must be examined.

The system does not determine specimen adequacy; use your standard lab protocol. To estimate the cellularity of the preparation in scantly cellular specimens, a specimen adequacy check can be per formed during a review of the 22 fields of view. This is done by counting the cells presented in each

of the 22 fields of view presented by the ThinPrep requirements for the average number of cells in each field dependent upon the microscope objective used:

The intensity of the mark indicator may be adjusted by using the knobs on the illumination control panel. The upper knob adjusts the intensity of the white light and the lower knob adjusts the intensity of the green light. (Refer to

Scan the entire field of view.

. The coordinates of the Object of Interest place it in the center of

FN 22 Eyepiece/

10X Objective

PREP DIAM mm AREA

Total Number of Fields

Number of Cells per Field for 5,000 Total

"Illumination Control Panel" on page 2.10.)

Imaging System. The chart below lists the

FN 22 Eyepiece/

40X Objective

Number of Total Number of Fields

Cells per

Field for

5,000 Total

20 314.2 82.6 60.5 1322 3.8

Autolocate presents in geographic order the 22 fields of interest as identified by the Image Processor to the CT for review. During review, the operator may:

• Focus, as necessary

3.10

• Move among the fields of view by pressing the

• Move the field of view by manipulating the joystick

• Change the objective magnification by using the

• Add and remove electronic marks by using the

• Press the

Review Scope Operator’s Manual

Cancel

key to cancel review at any time

and

Objective

Mark

button

buttons on the pod

OPERATION OF THE REVIEW SCOPE

Autolocate

22 of 22

Complete

Review Scan

Autolocate

22 of 22

Complete

Scan Finish

This is displayed if one or more electronic marks were made. Proceed with the next section.

This is displayed if no electronic marks were made. (Scan of the cell spot is optional.) Proceed with Check Slide Registration.

AUTO REVIEW (continued)

To proceed to the next field of view, press the pod to go back to the previous field of view (unless you are at the first one). If the objective is at 40X when the ceeding.

The object(s) of interest are not necessarily presented in the exact center of the field of view. The joystick can be used to move the stage for viewing and to position an abnormality in the target zone of the mark indicator for electronic marking.

Note:

Press the

Press the sion of slide review. The mark indicator highlight will turn from white to green when it has been selected. Pressing the white and the electronic mark to be removed.

Note:

When all 22 fields have been viewed, an audible beep will sound. The console display indicates the Autolocate function is complete.

button is pressed, the objective will automatically return to 10X before pro-

Be sure to position the object so that the physical mark will not obscure it.

Objective

Mark

Electronic marking can only be done while at 10X. The mark indicator is not visible at 40X.

button on the pod to toggle between 10X and 40X magnification.

button on the pod to electronically ‘tag’ an area for physical marking at the conclu-

Mark

button a second time will cause the mark indicator to turn from green to

button on the pod. Press the

Screen the entire field of view!

button on the

After all 22 fields of view have been presented, the stage will position the field of view at the top edge of the cell spot.

Review Scope Operator’s Manual

3.11

OPERATION OF THE REVIEW SCOPE

Review

1 of 3

Press Next

Scan

Finish

AUTO REVIEW (continued)

To estimate the cellularity of the preparation in scantly cellular specimens, a specimen adequacy

check can be also performed. In accordance with Bethesda 2001 criteria should be counted along a diameter of the cell spot that includes the center. Dependent upon the microscope objective used, use the chart below and count the average number of cells in each field. If this step is necessary, use the joystick to traverse the cell spot.

, a minimum of 10 fields

FN 22 Eyepiece/

10X Objective

PREP DIAM mm AREA

20 314.2 82.6 60.5 1322 3.8

The Bethesda System For Reporting Cervical Cytology, Second Edition, 2004, 1994 Spring Science and Business Media, LLC.

Total Number of Fields

Number of Cells per Field for 5,000 Total

FN 22 Eyepiece/

40X Objective

Total Number of Fields

Number of

Cells per

Field for

5,000 Total

Review Marked Fields

If areas on the slide were electronically marked, they may be reviewed prior to scanning the slide. This function is optional and does not have to be done to complete the slide review procedure. To review marks, press the

Review

soft key.

The display lists how many electronic marks were made. Similar to operation of the Autolocate function, the Review Marks function allows the operator to:

• Move among electronic marks using the

• Move the field of view by manipulating the joystick

• Change the objective magnification by pressing the

• Add and remove electronic marks by using the

All marks are presented at 10X magnification. The objective will be returned to 10X prior to advancing to the next location. When the desired marks have been reviewed, press the ceed to slide scanning.

3.12

Review Scope Operator’s Manual

and

Mark

buttons on the pod

Objective

button

Scan

soft key to pro-

Slide Scanning

Scan Paused 0% Complete

Press Next

Review

Scan Paused

29% Complete Press Next/Prev.

Reset Review

CAUTION:

Autoscan must be done if any electronic marks have been made.

OPERATION OF THE REVIEW SCOPE

AUTO REVIEW (continued)

The slide may be scanned whether any electronic marks have been made or not.

must

marks have been made, the entire slide

tion, enabling scan coverage of the entire cell spot. User preferences regarding method of scan, direction of scan and speed of scan may be customized in the preference menu. Preferences for scan mode must be set up ahead of time, in the user preference menu. (Refer to setting preferences on

Slide scanning must be performed to complete slide review if electronic marks have been made.

To proceed with Autoscan, press the entire cell spot in a defined path at 10X objective.

For Automatic Continuous or Automatic Start/Stop scan modes, to pause while scanning the slide, press the

button on the pod. The stage motion will cease.

be scanned

button on the pod. The motorized stage will present the

. The Review Scope has an Autoscan func-

If any electronic

page 4.13.)

The operator may:

• Press the

deleted)

• Press the

Start/Stop option; only goes back one field of view)

CAUTION:

bration should be performed. Refer to page 4.4.

•

During scan

(The speed remains until the scan ends, or the joystick is moved again.)

•

During pause

Review

Reset

If the stage drifts (movement without touching the joystick), a joystick cali-

soft key to review electronic marks, (electronic marks may be added or

soft key to start the scan at the beginning

button on the pod to go back to the previous field of view (only on Automatic

, move the joystick left to slow the scan speed, right to increase the scan speed.

, move the joystick to view a different area of the slide

Review Scope Operator’s Manual

3.13

OPERATION OF THE REVIEW SCOPE

Scan Paused

100% Complete

Finish

Creating Marks

1 of 3

Mark Verify

1 of 3

Press Next

Reject

Good Poor

Mark Rejected

Erase Marks

Continue

Slide Review

Cancelled

Continue

Confirm Reject

Yes No

AUTO REVIEW (continued)

• Press the

off)

An audible beep indicates the completion of scanning. The display shows Scan Paused, 100% Complete.

Physical Marking of the Slide

Press the marker pen. The display indicates marking activity (the number of marks depends on how many were electronically marked during review):

Finish

button on the pod to resume scanning (from the location where the scan left

soft key. Any electronic marks will be physically marked on the cover slip with the

When the physical marks have been made, they are presented for final approval. This is to ensure that the physical marks coincide with the electronic marks.

If the physical mark is acceptable, press the

If the mark is not acceptable, press the to erase pen marks on the slide. Review of the slide is canceled.

3.14

Review Scope Operator’s Manual

Reject

button on the pod to continue.

soft key. The display prompts to confirm the reject and

OPERATION OF THE REVIEW SCOPE

Confirm 1st Mark

Press Next

Reject

Confirm 2nd Mark

Press Next

Reject

Mark Rejected

Erase Marks

Continue

Slide Review

Cancelled

Continue

Creating Slide

Reviewed Mark

Please Wait ...

Slide Reviewed Mark (Auto Review Location)

AUTO REVIEW (continued)

Check the Slide Registration

If all of the physical marks have been accepted, the stage positions the slide to show the first fiducial mark. The slide registration is checked to confirm that there has been no slide movement or loss of stage position during slide review.

If the fiducial mark is aligned with the illuminated mark indicator, press the

If the second fiducial mark is properly aligned, press the

If the fiducial mark is not aligned, press the on the slide and the review of the slide is canceled.

Creating the Slide Reviewed Mark

If the slide registration is acceptable, upon pressing the to the Server, including the serial number of the review station, operator ID, date/time of the slide review, slide-review-complete status, coordinates of any marks that were made.

The stage positions the slide to receive the Slide Reviewed Mark. The marker pen is uncapped and a small double line is marked on the coverslip, located near the top arc of the slide. This indicates that a slide has completed the entire Auto Review process.

Reject

soft key. The display prompts to erase pen marks

button.

button on the pod, the slide data is sent

button on the pod.

Review Scope Operator’s Manual

3.15

OPERATION OF THE REVIEW SCOPE

Review Complete

Unload Slide

Load Slide

Press Next

Manual Menu

SECTION

Slide Already

Reviewed

Continue

If you do not wish to do a Subsequent Review, press the

Cancel

soft key on

the console.

An audible beep indicates the mark has been created. The display indicates slide review is complete. The slide may be removed from the slide holder. The Load Slide screen is displayed and the Review Scope is ready for another slide review.

Logout When Finished

When finished reviewing slides, logout to save your preferences settings. (Refer to Menu Option 1 Login/Logout,

page 4.3.)

SUBSEQUENT REVIEW

A slide that has undergone Auto Review may be reviewed again.

• More marks may be added (up to a total of 30 marks on any slide)

• No previous marks can be eliminated

• Up to 10 subsequent reviews may be performed

To conduct a subsequent review:

Power On

User Login

Load Slide

slide data record in the server database indicates a previous review has taken place.

- same as Auto Review.

- same as Auto Review. A “Slide Already Reviewed” message will display, because the

Press the

3.16

Continue

Review Scope Operator’s Manual

soft key.

OPERATION OF THE REVIEW SCOPE

Autolocate

4 of 22

Press Next/Prev

Review Finish

Review

1 of 3

Press Next

Scan

Finish

SUBSEQUENT REVIEW (continued)

Autolocate

Because the entire slide has been screened previously [at least once], you may skip to review or finish at any time. If scanning the slide is desired, press the

Review Marked Fields

If additional electronic marks are made, the display will increase the tally to show total number of electronic marks associated with that slide. Any newly marked fields will be presented first, then marked fields from the previous review(s).

- same as Auto Review. Notice that the soft keys are

Review

- same as Auto Review

soft key.

Review

and

Finish

Autoscan

Physically Marking the Slide

Verify Marks

marks are rejected.

Check Registration

the fiducial mark alignment is rejected.

Creating Slide Reviewed Mark

reviewed mark.

Unload Slide

Logout When Finished

When finished reviewing slides, logout to save your preferences settings. (Refer to Menu Option 1 Login/Logout,

- same as Auto Review.

- same as Auto Review. Only new marks are made on the slide.

- same as Auto Review, EXCEPT you will not be prompted to erase marks if the

- same as Auto Review, EXCEPT you will not be prompted to erase marks if

- Not performed. Only the initial slide review will create the slide

- same as Auto Review.

page 4.3.)

Review Scope Operator’s Manual

3.17

OPERATION OF THE REVIEW SCOPE

SECTION

Load Slide

Press Next

Manual Menu

Enter Login ID

Offline

At the Login ID display, press the Offline soft key.

From the Load Slide display, press the Manual soft key.

Load Slide

Offline

Manual Menu

Display when there is no interaction with Server (offline)

Display when interacting with Server (on line)

MANUAL SLIDE REVIEW

ThinPrep slides may be manually reviewed and marked at the Review Scope. Manual Review is always an available option. It will be required in certain conditions, which include:

• Slide not imaged (the slide has not been imaged by the Image Processor)

• “Slide Data Error” message (the slide was imaged but there is an error in the data that makes

it unavailable for Auto Review)

• Slide rejected by the Image Processor during imaging (too dense, too scant, too many bubbles,

etc.)

• No communication with the server is available

• Other problems such as a slide physical defect, incorrect labeling or incorrect coverslipping

Accessing Manual Review Mode

Manual Review mode may be accessed at Login display (via the menu) or at the start of a new slide review during Auto Review.

Press the menu)

3.18

Offline

Review Scope Operator’s Manual

soft key when the Enter Login display appears (either at power up, or via the

OPERATION OF THE REVIEW SCOPE

Align Cell Spot

With Indicator

Press Next

Align Cell Spot

With Indicator

Press Next

MANUAL REVIEW (continued)

At the Load Slide display, press the

Note:

Load a slide onto the stage. (Refer to Figure 3-2.)

Press the

Manual Review cannot make use of the fiducial marks that are printed on the ThinPrep® Microscope Slides. In order to create a reference coordinate for physically dotting the slide at the end of review, the operator must align two edges of the cell spot with the mark indicator.

Look through the eyepieces and using the joystick, move the cell spot up or down to align the

tom edge

movement is allowed on the joystick. (Refer to

When working offline, all user preferences will be set to default values. Refer to Preferences, page 4.13, to temporarily set preferences for an offline screening session.

Manual

of the cell spot with the inner surface of the illuminated ‘L’ indicator mark. Only vertical

soft key and the following screen will display.

Manual

soft key.

bot-

Figure 3-4‚ Align Cell Spot.)

Note:

Press the

Next, the second alignment is made. Look through the eyepieces and using the joystick, move the cell spot left or right to align the indicator mark. Only horizontal movement is allowed on the joystick. (Refer to Spot.)

It is important to try to align along the may be easily recognized later.

button on the pod when satisfied with the first alignment.

left edge

of the cell spot with the inner surface of the illuminated ‘L’

edge

of the cell spot, rather than at a group of cells that

Figure 3-4‚ Align Cell

Review Scope Operator’s Manual

3.19

OPERATION OF THE REVIEW SCOPE

Align the cell spot ‘edge’ with the mark indicator.

Align 1st

Align 2nd

View 1st Alignment View 2nd Alignment

Scan Paused 0% Complete

Press Next

MANUAL REVIEW (continued)

Press the

Manual Scan/Review of the Cell Spot

To proceed with the scan, press the entire cell spot in a defined path at 10X magnification. The to advance the stage movement. The console display shows the progress of the cell spot scan in 1% increments.

button on the pod when satisfied with the second alignment.

Figure 3-4 Align Cell Spot

button on the pod. The motorized stage will present the

button on the pod must be pressed

3.20

Review Scope Operator’s Manual

The operator may:

Scan Paused

29% Complete Press Next/Prev.

Reset Review

‘Review’ soft key appears the first time you electronically mark.

Scan Paused

100% Complete

FinishReview

Creating Marks

1 of 3

OPERATION OF THE REVIEW SCOPE

MANUAL REVIEW (continued)

• Press the

• Move the joystick to view a different area of the slide

• Press the

Note:

An audible beep indicates the completion of scanning. The display shows Scan Complete.

Press the

Be sure to position the object so that the physical mark will not obscure it.

• Press the

deleted)

• Press the

Review

button on the pod to move to the next location

Object

Mark

Review

Reset

button on the pod to change magnification

button on the pod to electronically mark or unmark cells for physical marking

soft key to review electronic marks (electronic marks may be added or

soft key to restart the scan at the beginning

button on the pod to go back to the previous field of view

soft key to review electronic marks.

Press the

Physical Marking of the Slide

If any areas were electronically marked for physical marking, the pen dots the slide now. The number of marks count up until all marks are complete.

Finish

soft key to finish manual slide review.

Review Scope Operator’s Manual

3.21

OPERATION OF THE REVIEW SCOPE

Mark Verify

1 of 3

Press Next

Reject

Good Poor

Confirm 1st Mark

Press Next

Reject

Confirm 2nd Mark

Press Next

Reject

MANUAL REVIEW (continued)

When the physical marks have been made, they are presented for final approval. This is to ensure that the physical marks coincide with the electronic marks.

The pen mark should align within the illuminated ‘L’ shape of the Mark Indicator. If the physical marks are acceptable, press the

button on the pod to continue.

If the marks are not acceptable, press the

Note

: If the marks are rejected, the slide may be reviewed again at the Review Scope (the entire pro-

cess is repeated). The marks from the marking pen should be removed before viewing the slide again.

Check the Slide Registration

If all the marks have been accepted, the stage positions the slide exactly at the first cell spot alignment location. The slide registration is checked to confirm that there has been no slide movement or loss of stage position during slide review.

If the edge of the cell spot aligns with the illuminated mark indicator, press the pod. The stage moves to the second cell spot edge position.

Reject

soft key. The review of the slide is cancelled.

button on the

If the alignment is acceptable press the

If either of the positions do not align with the mark indicator, press the review will be cancelled. Any marks should be removed.

3.22

Review Scope Operator’s Manual

button.

Reject

soft key. The slide

OPERATION OF THE REVIEW SCOPE

Slide Review

Cancelled

Continue

Creating Slide

Reviewed Mark

Please Wait ...

Slide Reviewed Mark (Manual Review Location)

Review Complete

Unload Slide

Load Slide

Offline

Manual Menu

MANUAL REVIEW (continued)

When the cell spot alignment has been confirmed, the stage positions the slide to receive the Slide Reviewed Mark. The marker pen is uncapped and a small double line is marked on the coverslip, located on the bottom arc of the slide. This indicates that a slide has completed an entire manual review process.

An audible beep indicates the mark has been created. Slide review is complete and the slide may be unloaded from the slide holder. The display transitions to the “Load Slide” screen.

Another slide may be loaded for manual review.

Review Scope Operator’s Manual

3.23

OPERATION OF THE REVIEW SCOPE

SECTION

Illuminator Lamp Switch

Review Scope Power Switch

SHUTTING DOWN THE REVIEW SCOPE

Normal Shut Down

When you are finished screening slides, the Review Scope may be shut off.

Make sure there are no slides left on the stage. Turn off the illuminator lamp switch. Turn off the Review Scope power switch. (Refer to

The Review Scope may be covered with the dust cover provided with it.

Figure 3-5.)

Figure 3-5 Review Scope Lamp Switch and Power Switch

Taking the Instrument Out of Service (Extended Shut Down)

If the Review Scope is to be removed from service, or shut down for an extended time, follow the steps for normal shut down and unplug the instrument.

3.24

Review Scope Operator’s Manual

4. Software Menu

OPERATION OF THE SOFTWARE MENU

SECTION

Chapter Four

Operation of the Software Menu

INTRODUCTION

A User accessible software menu is available for calibration of the Review Scope components and to select user preferences. Refer to on the console keypad and the joystick and buttons on the pod. The display on the console provides visual user interface. An audible beep function is also used to indicate completion of some software tasks.

Figure 4-1‚ Review Scope On-line Menus. User input is via the keys

User preferences for joystick button setup and movement speed, autoscan type, speed and direction, autolocate speed and audible beep volume may be selected, saved or changed. A preference setting profile is associated with each User Login ID and is retrieved from the Server at the time of Login. Regardless of which RS one logs onto, the last saved configuration will be enabled at the time of User Login. Preferences may be changed at any time. Factory default settings may be restored from this menu.

Review Scope Operator’s Manual

4.1

OPERATION OF THE SOFTWARE MENU

1 Left/Right 2 Up/Down

1 Continuous 2 Auto ST/SP 3 Manual ST/SP

Reset Defaults

Beep Volume Setting

Configure Pod Buttons

1 Min Overlap 2 Medium Overlap 3 Max Overlap

Autolo. Speed Mark Indicator

Frame of Reference 1 User Based 2 Slide Based

Speed Setting

1 Logout / Login 2 Joystick Cal. 3 Setup Marker (Marker Setup) (Marker Cal.) 4 Preferences 5 Open Error Log 6 Usage Count

1 Scan Dir. 2 Scan Type 3 Scan Overlap 4 Autolocate 5 Joystick Setup 6 Beep Volume 7 Button Setup 8 Reset Defaults

Preferences

Load Slide

Press Next

Manual Menu

1 Logout 2 Joystick Cal. 3 Setup Marker

4 Preferences 5 Open Error Log 6 Usage Count

Back

To access the menus, at the Load Slide display, press the

The menu list appears as two ‘pages’ of options, both of which are shown here.

To select an option, press the corresponding number key on the console keypad. Press the

Back

4.2

Figure 4-1 Review Scope On-line Menus

soft keys to move from page to page of the menu.

Review Scope Operator’s Manual

soft key on the console.

OPERATION OF THE SOFTWARE MENU

SECTION

Enter Login ID

Enter Back

Confirm Logout

Yes No

1 Logout 2 Joystick Cal. 3 Setup Marker

MENU OPTION 1 LOGIN/LOGOUT

If the RS is offline (not communicating with the server), the menu option reads online, the menu option reads

is used to enter the three-digit operator ID at the start of a screening session at the review scope. As soon as the numbers are entered, the RS queries the server to confirm that the ID is valid. If any user preferences have been saved for that ID, they are immediately activated on the RS.

Note:

Logout

the Server.

The operator ID is setup via the User Interface at the Image Processor or server. Consult your lab manager or the Image Processor Operator’s Manual to address any operator ID issues.

is only available if user Login was successful and the Review Scope is actively connected to

• Logout is used to log out of the current session at the Review Scope.

• Logout is used to save preferences associated with a user Login ID. If any preferences have

been selected, they are not saved on the server until Logout has been performed.

Logout

; if the RS is

The menu options must be visible on the console display to activate a particular selection. Press 1 on the key pad to logout.

A display prompting confirmation of user logout appears. Press the logout is desired.

Yes

soft key on the console if

Review Scope Operator’s Manual

4.3

OPERATION OF THE SOFTWARE MENU

Enter Login ID

Offline

Load Slide

Press Next

Manual Menu

SECTION

Joystick Cal.

Move to extents

then center

and wait

The Enter Login ID display will appear if logout was successful.

If the user does not wish to logout, press the No soft key on the console. The software will display the Load Slide screen.

MENU OPTION 2 JOYSTICK CALIBRATION

The joystick is calibrated by the operator via the system menu.

4-button pod: calibration is recommended once daily or at the start of each shift.

5-button pod: calibration is necessary upon installation of the pod, or if the pod has been removed and then reinstalled on a Review Scope.

Note:

To calibrate the joystick, from the menu select

The display prompts for the joystick to be moved so that it reaches its furthest point of travel in all directions. This is necessary for calculating the calibration. To calibrate the joystick:

1. Place your finger in the center of the joystick. Deflect the button outward to the farthest possible

If drifting of the stage is noticed, calibrate the joystick.

2, Joystick Cal

extent.

4.4

Review Scope Operator’s Manual

OPERATION OF THE SOFTWARE MENU

Joystick

Deflect and circle 2 or 3 times

Joystick Cal.

Complete

Continue

Joystick Cal.

Failed

Continue

2. While maintaining full deflection, roll your finger in a circle 2 or 3 times to move the joystick in the widest possible circles.

3. Return the joystick to the center and let go.

4. Do not touch the joystick while calibration calculations are being performed.

Figure 4-2 Calibrate the Joystick

In a few seconds, the calibration is complete. An audible beep will sound and the display indicates the calibration is complete.

Press the

If calibration fails, retry it several times. If calibration continues to fail, contact Hologic Technical Support.

Continue

soft key on the key pad to return to the Load Slide screen.

Review Scope Operator’s Manual

4.5

OPERATION OF THE SOFTWARE MENU

SECTION

1 Marker Setup 2 Marker Cal.

Back

Load Blank Slide

Press Next

MENU OPTION 3 SETUP MARKER

Two object marker adjustments are available in this menu: Marker Setup, which adjusts the proximity of the pen tip to the slide for marking, and Marker Calibration, which calibrates the marker.

Marker Setup

Marker Setup adjusts the pen tip nearer to or further from the microscope slide when the pen is lowered for marking. Indications that adjustment is needed include:

• The pen mark is too wide (too close to the slide)

• The pen drags on the slide between marks (too close to the slide)

• Scant or no mark on the slide (too far from the slide)

Before changing the Marker Setup, confirm the pen is seated correctly in the holder. Do a Marker Calibration.

From the menu, select

A prompt to load a blank slide appears.

Load a blank ThinPrep slide into the slide holder on the stage. Press the

1, Marker Setup.

button on the pod.

4.6

Review Scope Operator’s Manual

OPERATION OF THE SOFTWARE MENU

Marker Setup

Focus

Continue

Focus

Marker Setup

Load Marker

Skip Done

Marker Setup

Next - Lower Pen

Prev - Raise Pen

Save



Next Button



Prev Button

Figure 4-3 Focus on the Painted Arc

Looking through the eyepieces, focus the microscope on the top arc of the frosted area. (Refer to Figure 4-3.) Press the

Continue

soft key when ready.

If a marking pen is already in the object marker holder, press the

If there is no pen present or you are replacing a pen, take a new pen, uncap it and prime the marker by gently dragging the tip across a piece of lint free tissue. Load the pen into the holder.

• For ThinPrep Review Scopes that use the Sharpie marking pen, push the pen into the guide,

making sure it is seated against the holder. Then press the locking arm to the right until it firmly grips the pen.

• For ThinPrep Review Scopes that use the Pilot marking pen, push the pen into the guide.

Loosen your hold on the pen and notice that it moves up slightly. Gently hold the pen there and press the locking arm to the right until it firmly grips the pen. Because the pen is thinner than the holder, it may be helpful to hold the pen at a 15° angle (approximately the 1 o’clock position on a clock face) in the guide, while pressing the locking arm.

Press the

Press the Observe the movement of the pen as either button is repeatedly pressed.

Done

softkey. (Refer to Figure 4-5.)

buttons on the pod to step the pen closer to or away from the slide surface.

Skip

soft key.

Review Scope Operator’s Manual

4.7

OPERATION OF THE SOFTWARE MENU

Load Blank Slide

Press Next

If the pen is too close to the slide (leaving wide marks or bent pen tip), click on the move the pen away from the slide. If the pen is not close enough to the slide, click on the to bring the pen tip closer to the slide.

Click on

WARNING:

Moving Parts

Save

to save the position.

Glass

button to

button

Marker Calibration

Calibration of the pen used for physically marking the slide positions the pen so that the ink mark is within the ‘L’ shape of the mark indicator. Minimally, calibration should be performed:

• Daily

• Every time a new marker is installed

• After a mark is rejected while verifying marks

Note:

The object marker on ThinPrep Review Scope model numbers 70575-001, 70575-003, 71062001, and 71062-002 uses an ultra fine tip Sharpie ThinPrep Review Scope model numbers 70669-001, 70669-002, and 70669-003 uses a Pilot extra fine marking pen. These pens are widely used for marking slides.

If using a 4-button pod, joystick calibration should be done before marker calibration.

marking pen. The object marker on

To calibrate the object marker, the Review Scope must be powered On. The lamp illuminator should be on and the white mark indicator lamp intensity should be turned up to a brightness for normal viewing.

From the menu, select option

Load a blank ThinPrep® microscope slide into the slide holder on the stage. Press the the pod.

4.8

Review Scope Operator’s Manual

3, Setup Marker

, and then select option

2, Marker Cal.

button on

OPERATION OF THE SOFTWARE MENU

Marker Cal.

Focus

Continue

Focus

Marker Cal

Load Marker

Skip Done

Figure 4-4 Focus on the Painted Arc

Looking through the eyepieces, focus the microscope on the top arc of the frosted area. (Refer to Figure 4-4.) Press the

Continue

soft key when ready.

If you are doing the routine calibration of the marker and a marking pen is already in the object marker holder, press the

If you are replacing the pen with a new one, remove the pen now.

CAUTION:

ing, the control arm moves it to a position that allows for the best access, and ensures that it seats most securely against the seal diaphragm.

Take a new pen, uncap it and prime the marker by gently dragging the tip across a piece of lint free tissue. Load the pen into the holder.

• For ThinPrep Review Scopes that use the Sharpie marking pen, push the pen into the guide,

making sure it is seated against the holder. Then press the locking arm to the right until it firmly grips the pen. (Refer to

Do not load the Sharpie marking pen until prompted to do so. During load-

Skip

soft key.

Figure 4-5.)

Review Scope Operator’s Manual

4.9

OPERATION OF THE SOFTWARE MENU

Lock

Unlock

Poor

Good

Lock

Unlock

Poor Good

Creating Mark

Please Wait...

Center Mark

Press Next

Figure 4-5 Load the Sharpie® Object Marker Pen

• For ThinPrep Review Scopes that use the Pilot marking pen, push the pen into the guide.

Press the

4.10

Review Scope Operator’s Manual

Done

Figure 4-6 Load the Pilot Object Marker Pen

soft key when the pen is loaded. A test mark will be made on the slide.

OPERATION OF THE SOFTWARE MENU

Correct

Incorrect

Marker

Calibration

Complete

Continue

Load Blank Slide

Press Next

The software prompts the user to center the mark in the illuminated mark indicator. Using the joystick, move the mark until it aligns within the boundaries of the ‘L’ shape of the mark indicator. (Refer to

Figure 4-7.)

Figure 4-7 Align the Pen Mark Within the Mark Indicator

Press the

An audible beep indicates the marker calibration is complete. Press the the Load Slide display. Unload the slide from the slide holder.

Prime the Object Marker

For Review Scopes that use the Pilot pen as the object marker, priming the pen may improve the flow of ink to the slide. Prime the pen after the marker has been set up and after the marker has been calibrated. Use the first several steps of the Marker Calibration process to uncap the marker.

From the menu, select option

button on the pod when ready.

3, Setup Marker,

and then select option

Continue

2, Marker Cal.

soft key to return to

Load a blank ThinPrep® microscope slide into the slide holder on the stage. Press the the pod.

button on

Review Scope Operator’s Manual

4.11

OPERATION OF THE SOFTWARE MENU

Marker Cal.

Focus

Continue

Focus

Slide a lint-free wipe under the pen tip.

Figure 4-8 Focus on the Painted Arc

Looking through the eyepieces, focus the microscope on the top arc of the frosted area. (Refer to Figure 4-8.) Press the

Slide a lint-free wipe between the pen tip and the slide

Continue

soft key when ready.

Figure 4-9 Prime the pen

Lift up the lint-free wipe so that it touches the pen top. When ink from the pen starts to flow freely to the lint-free wipe, the pen is primed and ready to use.

Press the cancel key Load Slide display. Remove and discard the lint-free wipe.

Note:

4.12

Alternatively, you can prime the Pilot marking pen by hand. Remove the pen from the holder, and press the pen against a lint-free wipe. In this case, the Marker Setup and Marker Calibra tion processes must be done after the pen is primed.

Review Scope Operator’s Manual

⊗

to omit the remaining steps in the Marker Calibration process and return to the

OPERATION OF THE SOFTWARE MENU

SECTION

1 Scan Dir. 2 Scan Type 3 Scan Overlap More

4 Autolocate 5 Joystick Setup 6 Beep Volume

Back More

7 Button Setup 8 Reset Defaults

Back

1 Left/Right 2 Up/Down

Save

MENU OPTION 4 PREFERENCES

Preferences allows the setting of user preferences including Autoscan settings and maximum speed for Autolocate. For each user-selectable preference, the console display shows the current setting of the parameter. Use the pod buttons to change the setting to the desired value. The setting is stored locally (in RS memory) until the user preferences are updated on the Server during user Logout.

Note:

From the main menu, select option select an option, press the corresponding number key on the console keypad. Press the soft keys to move from page to page of the menu.

Note:

Preferences 1 Scan Direction

The direction of the stage movement during autoscan can be selected. From the preferences menu, select

time to exit out of menus.

Preferences are not saved until Logout. At the next Login, the preferences for that User ID will be uploaded.

4, Preferences

Refer to the preferences worksheet at the end of this chapter, when evaluating and recording

preference settings.

1, Scan Dir

. The direction options are Left/Right or Up/Down. Press the cancel key

. All three ‘pages’ of the menu are shown below. To

Back

⊗ at any

On the console keypad press the number key corresponding to your choice. The selected direction

Save

will have a highlighted box around it. Press the tion setting will now be used during this login session and will be saved to the user preferences profile at logout.

soft key to save that preference. The scan direc-

Review Scope Operator’s Manual

4.13

OPERATION OF THE SOFTWARE MENU

Preferences 2 Scan Type

The autoscan function presents the entire cell spot in a defined path at 10X magnification. Three types of scan motion are selectable:

•

Automatic Continuous

across the cellular region, with each pass overlapping the previous scan. The user may speed up or slow down the movement by moving the joystick to the

left

for a slower scan. Scan motion may be paused and resumed (from where the scan was

interrupted) by pressing the

•

Automatic Start Stop

overlapping fields of view, including a pause at each view. The user may increase or decrease the duration of each pause by moving the joystick to the for a slower scan. Scan motion may be paused and resumed (from where the scan was interrupted) by pressing the

•

Manual Start Stop

which is a series of discrete, overlapping fields of view (identical to the Auto Start-Stop pat tern). The autoscan is paused after each field of view and remains there until the user presses

the

button again.

- Scan motion is initiated by the RS and consists of steady movement

right

for a faster scan and to the

button on the pod.

- Scan motion is initiated by the RS and consists of a series of discrete,

right

for a faster scan and to the

button on the pod.

- Using the

button on the pod, the user initiates the scan motion,

left

To set the preferred scan type, select option

Note:

In order to have a visual reference during the speed and direction test functions, load a test slide in the stage slide holder prior to selecting the preferences. If a slide is not present, the display will prompt you to load one.

2, Scan Type

4.14

Review Scope Operator’s Manual

Hologic ThinPrep Operator's Manual

Specifications and Main Features

Frequently Asked Questions

User Manual