Intan Technologies CLAMP User Manual

Intan CLAMP System

Intan CLAMP System

Voltage/Current Clamp

User Guide

16 September 2016; updated 14 May 2019

Features

♦ Complete, miniaturized patch clamp amplifier system

with small digital headstages using revolutionary
CLAMP microchips from Intan Technologies

♦ Voltage clamp operation with low current noise floor:

< 3 pA

♦ Current clamp operation with low voltage noise floor:

< 20 µV

♦ Fast transient capacitance compensation: 0-20 pF

range; bridge balance in current clamp mode

♦ Automated measurement of pipette / seal resistance

and cell membrane parameters

♦ Clamp operation controlled by software and/or external

analog voltage command signals

♦ Small headstage size: 6.1 cm × 2.8 cm × 2.0 cm (not

including pipette holder)

♦ Standard threaded Teflon pipette electrode connector
♦ Standard dovetail for mounting to micromanipulator
♦ All-digital interface cable is immune to noise pickup
♦ Standard USB interface to host computer
♦ Free, open-source, multi-platform GUI software

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over 5 kHz bandwidth with highest sensitivity

rms

over 10 kHz bandwidth

rms

Description

The Intan Technologies CLAMP patch clamp amplifier
system allows users to perform signal channel or multi­channel patch clamp electrophysiology or electrochemistry
experiments using the revolutionary new Intan CLAMP
voltage/current clamp chips.

The Intan CLAMP system incorporates all analog circuitry
and many digital control blocks in close proximity to the
electrode, resulting in a miniaturized “headstage” that is
actually a complete patch clamp amplifier. Thanks to the
integration of nearly all patch clamp circuit elements onto a
single silicon chip, the Intan-powered patch clamp amplifier
is smaller than traditional analog headstages that perform
only a small fraction of the total amplification task.

The Intan digital CLAMP headstages are interfaced to the
Intan CLAMP Controller which coordinates the operation of
the voltage/current clamps as well as sampling auxiliary
digital and analog signals in synchrony with the measured
electrophysiological signals. The interface cables are purely
digital with independently isolated grounds, making them
immune to noise pickup or signal degradation.

The Intan CLAMP Controller connects to a host PC via a
standard USB bus, and operates using free, open-source
software.

Intan CLAMP System

System Architecture and Theory of Operation

Traditional Analog Patch Clamp Amplifier

The diagram above shows the major functional components of a traditional patch clamp amplifier system. A traditional analog
headstage module contains sensitive analog electronics that act as a pre-amplifier with voltage clamp and current clamp capability.

In voltage clamp mode, the headstage measures the electrode current and converts this to a proportional small voltage. In current
clamp mode, the headstage buffers the electrode voltage but provides no additional amplification. Voltage and current clamp
control is provided by analog voltages that convey the desired clamping levels.

The headstage is connected to a remote computer-controlled amplifier via a shielded interface cable that carries small analog
voltages (typically in the millivolt range) and is thus susceptible to noise pickup. The amplifier module / digitizer consists of one or
more rack-mounted boxes that contain additional analog amplifiers, analog-to-digital converters (ADCs), digital-to-analog
converters (DACs), and a digital controller that coordinates control of these devices. The amplifier module and digitizer are
interfaced to a host PC that sequences particular experiments and records the measured data.

Intan Digital Patch Clamp Amplifier

The CLAMP chips from Intan Technologies combine all analog circuitry and many digital control blocks on a single chip, permitting
the construction of Intan-powered digital headstages (see diagram above). A small circuit board containing an Intan CLAMP
chip and a small number of support components form a complete patch clamp amplifier with a purely digital interface. The Intan
digital “headstage” is actually a complete, miniaturized patch clamp amplifier. Thanks to the integration of nearly all patch
clamp circuit elements onto a single silicon chip (see “actual size” inset above), the Intan-powered patch clamp amplifier is smaller
than many traditional analog headstages that perform only a small fraction of the total amplification task.

The digital interface cable uses a standard serial communication protocol (Serial Peripheral Interface, or SPI) and is no longer
susceptible to noise pickup. Sensitive analog signals are digitized at the source, not several meters away. The purely digital
interface makes it easy to electrically isolate each headstage and eliminate ground loops. The need for a large computer-controlled
amplifier module is completely eliminated, replaced by an Intan CLAMP controller that can easily control multiple digital
headstages simultaneously.

To preserve legacy “external command” and “signal monitor” functions associated with traditional patch clamp systems, the Intan
CLAMP controller incorporates ADCs and DACs to allow for real-time control of voltage and current clamp via analog voltages (in
addition to software clamp control), and real-time monitoring of measured and/or clamp voltages/currents via analog signals.

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Intan CLAMP System

The voltage clamp operates over a wide range with steps as

The current clamp produces currents up to ±127 nA and
steps as small as 5 pA. Intracellular voltages may be

. The plot below shows the intracellular

Intan CLAMP Headstages

An Intan CLAMP headstage is shown above with a pipette holder and glass pipette attached (not included). Intan headstages
mate with thread-mounted pipette holders that are compatible with Axon amplifiers. Pipette holders sold by Molecular Devices
(the 1-HL-U), Warner Instruments (the Q series), and other companies may be used with Intan headstages. Glass pipettes must
be custom made with a pipette puller shortly before recording.

Each headstage has standard 0.7” (17.8 mm) wide dovetail connectors on the side and the bottom. These mate with
micromanipulators from companies such as Sutter Instruments to permit precision positioning and movement of the headstage.

The rear side of the headstage has a receptacle for a 1-mm diameter grounding pin. This should be used to tie the headstage to
a grounding point near the experiment. Intan headstages are electrically isolated from the controller and from earth ground; this
can prevent noise pickup caused by unintentional ground loops. If a Faraday cage is used, it should be connected to the black
I/O GND binding post on the rear panel of the controller. Some experimentation may be needed to find the optimal grounding
scheme for a particular patch clamp rig.

The blue interface cable delivers ±3.3V power to the headstage and provides a digital serial interface between the headstage and
the controller. These SPI (serial peripheral interface) cables use low-voltage differential signaling (LVDS) with twisted-pair wires
for noise-free operation. Each Intan CLAMP headstage comes with a 6-foot (1.8-meter) interface cable. Additional SPI interface
cables may be purchased from Intan and daisy-chained to span longer distances.

Each headstage contains a small circuit board with an Intan CLAMP1 chip that performs all voltage and current clamping and
voltage and current sensing (see previous page). The detailed operation of this microchip is described in the Intan CLAMP
Voltage/Current Amplifier Chip Datasheet, available from the Downloads page of the Intan website.

The figures below show actual data obtained using an Intan CLAMP system.

small as 2.5 mV. A low noise floor (below 3 pA
sensitive range) allows tiny currents to be resolved. The plot
below shows a cell membrane test:

in the most

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observed across a wide ±300 mV range with a noise floor
below 20 µV
potential of a neuron during current injection:

rms

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Intan CLAMP System

Controller Hardware

Front Panel

The front panel of the Intan CLAMP Controller provides connection ports for Intan CLAMP headstages as well as auxiliary digital
and analog inputs. From left to right:

• Intan CLAMP headstage ports: These ports, labeled A and B, provide connection points for up to two headstages via
12-wire digital SPI (serial peripheral interface) cables. Each headstage port is electrically isolated from the controller
and from earth ground. Indicator lights provide information on the status of each port: green and yellow LEDs show that
proper voltage supplies are being provided for each headstage. Red LEDs are activated when the software recognizes
a headstage plugged into a port.

• Digital inputs: Two BNC sockets are provided for recording digital signals in synchrony with the headstage signals.
The digital inputs accept TTL-level signals. Any voltage between 0V and +0.8V is read as a digital “low”. Any voltage
between +2.0V and +5.5V is read as a digital “high”. Voltages delivered to these sockets should not exceed the range
of 0V to +5.5V. These signals may be used to record discrete events associated with an experiment.

• Analog inputs: Two BNC sockets are provided for recording general-purpose analog signals, or for controlling the
headstages using externally provided analog waveforms. Signals are digitized with 16-bit ADCs over a range of -10.24V
to +10.24V. Voltages delivered to these sockets should not exceed this range.

• Status indicators: Status indicator A is illuminated when the CLAMP Controller software has successfully connected
to the unit. Status indicator B is controlled by DIGITAL IN 1; status indicator C is controlled by DIGITAL IN 2. These
LEDs can be used to monitor the status of digital signals that are recorded in synchrony with the patch clamp amplifiers.

• Power indicator: This red LED is illuminated when the Intan CLAMP Controller is powered.

Rear Panel

The rear panel of the Intan CLAMP Controller provides auxiliary output lines as well as other ports and switches. From left to right:

• Analog outputs: Two BNC sockets are provided for monitoring measured signals or clamp signals from CLAMP
headstages. The headstages communicate with the controller using purely digital signals, but 16-bit DACs are used to
reconstruct analog signals with desired scaling factors. The control software allows users to route selected signals to
any analog output ports. These ports have a -10.24V to +10.24V voltage range.

• Audio line out jack: This standard 3.5-mm stereo phone jack allows users to connect an audio amplifier to the controller
and listen to the signals routed to the two analog output ports. ANALOG OUT 1 is connected to the left channel;
ANALOG OUT 2 is connected to the right channel. This port cannot drive speakers directly; an audio amplifier should
be used, and the volume should be adjusted carefully to ensure that excessive levels are not delivered to speakers.

• High-speed port: This connector is reserved for future use.

• I/O expansion port: This connector is used to add an Intan I/O Expander. This board is described in the next section.

It provides six additional analog inputs and outputs and 14 additional digital inputs and outputs for more complex
experiments. Signals on this port are digital and serially encoded, and are not easily accessed without the I/O Expander.

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Intan CLAMP System

• CONFIG switches: Configuration switches 1-3 are reserved for future use. Switch 4 (CONFIG4) is used to select the
voltage level of the digital output ports (see next item). With CONFIG4 in the down position, 3.3V digital signals are
generated. With CONFIG4 in the up position, 5.0V digital signals are generated.

• Digital outputs: Two BNC sockets produce either 3.3V or 5.0V digital signals (see previous item) that can be
synchronized with software-generated voltage clamp or current clamp waveforms.

• USB port: A USB 2.0 port provides two connection to a host computer running the control software.

• Sample clock out: This port generates a digital square wave proportional to the headstage sampling rate when the

headstages are active. While the software acquires data with a sampling rate of 50 kS/s, the headstages are actually
sampled at 200 kS/s to reduce noise, so this port produces a 200 kHz square wave during operation. The voltage level
of this signal is set by the CONFIG4 switch.

• Mark out: This port generates digital pulses marking the onset and offset of voltage clamp or current clamp waveforms.
The voltage level of this signal is set by the CONFIG4 switch.

• I/O GND: This binding post is connected to the controller system ground used by all analog and digital inputs and
outputs. This is the preferred ground to use for Faraday cage and other shielding connections.

• Chassis GND: This binding post is connected to the controller chassis and to the grounding conductor of the AC power
socket.

• Power switch and fuse holder: The unit uses two standard 1A 250V 5x20mm slow blow fuses that can be replaced
by opening the fuse holder to the right of the power switch. The power cord must be removed to access the fuses.

• AC power socket: The controller is powered by 90-260V AC power, and is compatible with international voltage levels.
A US-style power cord is supplied with the controller. International customers must use an adapter to accommodate
non-US power sockets. The center grounding conductor must be connected to earth ground to avoid electric shock
hazards.

Mounting

The Intan CLAMP controller can be rack mounted on a standard 19” instrument rack using provided hardware, or it can be used
on a bench top by folding out the feet on the bottom of the case:

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