3Brain BioCAM X Manuale utente
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Welcome to
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Last updated 25.09.2019
User Guide
Essentials
Contents
5Introduction
6MEA technology
6CMOS-MEA technology
8At a glance
9Overview
10 BioChip
11 BioCAM X
13 Host PC
13 Desktop PC
13 Laptop PC
14 BrainWave X
15 Precautions
16 BioCAM X handling and use
17 BioChip handling and use
18 Cleaning procedure for BioChips
19 Sterilization procedure for BioChips
20 Get started
21 Install the BioCAM X
21 Desktop host PC
21 Laptop host PC
22 Plug the BioChip
23 Setupanonpre-conguredhostPC
23 Verify proper functioning
24 Quickguidetoyourrstuse
25 Basic concepts
25 Visualization of data
26 MEA Viewer control
27 Data formats
28 Online mode (Record mode)
28 Important notes
28 Open recorder
29 Visualize live data
30 BioChip Calibration
31 Record live data
32 Oinemode(Playbackmode)
32 Open recorded data
33 Quick analysis and save of results
34 Visualize recorded data
35 Understandingmaincontrolsaectinggraphs
Introduction
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Welcome to the BioCAM X platform and thank you for your purchase. The BioCAM X platform is among
the most advanced systems for managing your experiments on the emerging generation of high-den-
sity CMOS-MEAs. This manual has been written to help you to take advantage of all functionalities
provided by your BioCAM X. Be sure to read this manual thoroughly, and to keep it handy when using
the BioCAM X platform.
Before any use of your BioCAM X platform, please read the “Precautions” on page 15, which contains
relevant information to preserver your BioChips and BioCAM X from possible damages.
MEA technology
Amongthedierentmethodologiesusedforelectrophysiologicalmeasures,metalmicroelectrodesin-
tegrated on-chip can provide multisite measures of extracellular signals with a high signal-to-noise ratio.
In addition, by applying voltage or current stimuli to the same microelectrodes it is possible to depolar-
ize cells or tissues, thus establishing bi-directional interfaces. As established over several decades of
research, both sensing and actuating performances of microelectrodes can be applied to study a wide
range of electrogenic cells and tissues, including neuronal and cardiac preparations.
Conventionalmicroelectrodearrays(MEAs)arebio-sensingchipsrealizedbymeansofthin-lmtech-
nologies and do not integrate on-chip any microelectronic circuit. Therefore, conventional MEAs are
passive devices made on silicon, glass or polymeric substrates. Each microelectrode can be made by
dierentmaterials(e.g.Pt,IrOx,TiN)anditisindividuallywiredon-chipandconnectedtoanexternal
amplieranddataacquisition(DAQ)instrument.DuetotheneedofthisMEAtechnologyofindividually
routing on-chip each electrode, space constraints and wiring encumbrance impede the realization of
dense and large electrode arrays. Thus, for conventional MEAs the typical electrode pitch is in the range
of 100 µm and the array includes from 60 up to 256 microelectrodes. In addition, given the distance
betweentheelectrodesandtheo-chipampliersandtheuseofinterconnectingwires,conventional
MEAs are subjected to inductive coupling noise.
CMOS-MEA technology
The electrode density and array sizes can be increased by changing the technology used to realize
microelectrode arrays (MEAs). High-density MEAs are realized with complementary metal–oxide–semi-
conductor technology (CMOS), as it is done for microelectronic devices (e.g., computer microproces-
sors) and light-imaging devices (e.g., camera sensor), and with post-processing methods to optimize the
electrode performances.
Briey,theCMOStechnologyallowstorealizeactiveelectrode-pixelsthatintegrateinsmallareasofa
fewsquaremicrometerselectrodes,ampliersandsignalconditioningcircuitsin-pixel,justunderneath
eachelectrodesite.On-chip,additionalamplicationstages,multiplexingandhigh-speedaddressing
circuits are provided.
In particular, the circuit architecture of 3Brain’s BioChips is based on the Active Pixel Sensor concepts,
as commonly used for light imaging CMOS cameras, and was designed to allow full array recordings at
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sucientlyhighsamplingfrequencyforeachelectrode.
InBioChipsthelocalin-pixelbuersunderneatheachelectrodeallowtolocallyadaptsignalsfromhigh
impedance (electrode-side) to low impedance (wiring-side) to avoid the induction of coupling noise
fromelectricalwiringbeforeamplication.Additionally,theon-chipmultiplexingandaddressingcircuits
allow to minimize the number of wiring outputs even though the large number of electrodes that have
tobesimultaneouslymeasured.Indeed,eachelectrodesignalisnotindividuallywiredo-chip.Rather,
signalsofmultipleelectrodesaremultiplexedathighfrequencyoverafewnumberofwires.Inthisway,
several thousands of electrodes can be recorded on only a few tens of output wires.
The in-pixel circuit implemented in BioChips allows recordings from a large signal bandwidth that
includeseldpotentialsandspikes.InsteadofimplementinganAC-couplingsolutionthatwouldrequire
largeareasfortheintegrationofadequatecapacitors,theBioChipsin-pixelcircuitintegratesanau-
to-zeroing circuit that is regularly calibrated to the electrode DC voltage and that subtracts this cali-
bratedDCvoltagefromtheelectrodesignalbeforetherstamplicationstage.Thisprocessiscalled
calibrationanditalsoallowstoadaptthecircuitperformancetodierentexperimentalconditions.In
particular,allCMOSdevicesarephotosensitiveandphoto-generatedchargesgiverisetodierentDC
driftingtimesthatcanbringin-pixelamplierstosaturate.BioChipsmitigatetheseeectsandhence
allowexperimentsunderlightstimulationconditions(asrequiredforinstanceforretinastimulation)by
usinghighercalibrationfrequenciestokeeptheDCinputsignaltotheworkingpointoftheamplierand
toavoidthesaturationoftheamplier.
At a glance
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Overview
The BioCAM X platform is a high resolution electrophysiology system capable to perform in-vitro elec-
trophysiological measures on electroactive cells and tissues. Even though, to some extents, the plat-
form has some similarities with more conventional Microelectrode Array (MEA) systems, it is a radically
newtechnologytoperformextracellularmeasures.DierentlythanconventionalMEAsystems,the
BioCAM X platform relies on active CMOS-MEA chips, which integrate thousands of miniaturized active
electrodes over large areas. Combined to sub-millisecond temporal resolution, the dense integration of
electrodes results in a spatial resolution that enables novel analysis, can increase the statistical signif-
icance of your experiments and opens new imaging approaches to investigate electroactive prepara-
tions.
The 3Brain’s BioCAM X platforms was tested so far for in-vitro electrophysiological experiments on
neuronal cell cultures, brain slices, retina preparations and cardiac cultures. Electrophysiological signals
rangingfromsloweldpotentialstofastsinglecellspikingactivitycanberecordedsimultaneously.
ExamplesofrecordingsprovidedbydierentlaboratoriesusingtheBioCamplatformsareavailableon
the 3Brain website and uploads of novel examples based on your research are warmly welcome.
Overall, the platform consists of three basic components: A) a multiuse BioChip cartridge available in
dierentmodelsandincorporatingtheCMOS-MEAsiliconchip;B)theacquisitionBioCAMXhardware
thatreadsoutelectrophysiologicalsignalsfromtheBioChip;C)thehostPCequippedwiththeacqui-
sitionboardandtheBrainWaveXsoftwaretoacquire,visualize,storeandanalyseexperimentaldata
recorded with the BioCAM X platform.
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BioChip
The BioChip cartridge integrates on an electronic substrate the CMOS-MEA chip and a reservoir cham-
ber to maintain cultures or tissues contacting the electrode array either under cell culture media or per-
fused media, respectively. The cartridge is 54 mm x 54 mm (2-1/8 in x 2-1/8 in) in size and is conceived
to be placed in an incubator for cells or tissue cultures.
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Contact pads
: gold-plated pads for connection between the BioChip and the BioCAM X. Properly
cleaned and non-oxidized pads are needed for a stable connection.
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PCB
:theprintedcircuitboardsubstrateoftheBioChip.Dierentcolorsareavailableandaccordingto
the layout of the CMOS-MEA.
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Glass ring
:borosilicateglassringdeningthereservoir.Externaldiameter28mm(1-7/64in),internal
diameter 25mm (0-63/64 in), height 5mm (0-13/64 in).
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Reservoir
: chamber for the bath solution used for the biological preparation. The volume of solution
that can be contained is of about 2mL.
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CMOS-MEA
: chip integrating thousands of active electrodes for high-resolution electrophysiological
recordingsfromcellsortissuesplacedonitsactivearea.Dierentapplication-specicMEAlayouts
according to the BioChip model are available.
Contact pads
Glass ring
PCB
Reservoir
CMOS-MEA
Indice
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