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In vivo measurements with a 64-channel extracellular neural recording integrated circuit

Abstract

This paper presents in vivo measurements obtained from an implantable 64-channel neural recording Application Specific Integrated Circuit (ASIC) developed at IMSE and gives details of the computer interface used for real-time data acquisition. This interface connects the ASIC to a conventional 2.0 USB port by means of a Field Programmable Gate Array (FPGA). Communications are bidirectional and employ custom protocols both for delivering commands to the ASIC and for recording neural information under different channel selection and operation modes. The link is controlled by a user-friendly programming interface written in C++ which includes a built-in routine to efficiently index and store the captured data. Measurements demonstrate the suitability of the ASIC for capturing local field and action potentials with two different microelectrode array platforms.

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In vivo measurements with a 64-channel extracellular neural recording integrated circuit

Author: Delgado Restituto, Manuel; Rodríguez Pérez, Alberto; Darie, Ángela; Rodríguez Vázquez, Ángel Benito; Soto Sánchez, Cristina; Fernández Jover, Eduardo
Publisher: Institute of Electrical and Electronics Engineers
Year: 2014
DOI: 10.1109/ICECS.2014.7050028
Source: https://idus.us.es/bitstreams/70608e04-ba91-49f6-a314-e7c10f5f8874/download
In i o measu emen s wi h a 64-channel
ex acellula neu al eco ding in eg a ed ci cui
Manuel Delgado-Res i u o, Albe o Rod íguez-Pé ez,
Angela A. Da ie and Ángel Rod íguez-Vázquez
Ins i u e o Mic oelec onics o Se ille
(IMSE-CNM) CSIC, Uni e si y o Se ille
Email: {mandel, albe o, angela, angel}@imse-cnm.csic.es
C is ina So o-Sánchez and Edua do Fe nández-Jo e
Bioenginee ing Ins i u e, Uni e si y Miguel He nandez
Email: {cso o, e. e nandez}@goumh.umh.es
Abs ac —This pape p esen s in i o measu emen s ob ained
om an implan able 64-channel neu al eco ding Applica ion
Specific In eg a ed Ci cui (ASIC) de eloped a IMSE and
gi es de ails o he compu e in e ace used o eal- ime da a
acquisi ion. This in e ace connec s he ASIC o a con en ional
2.0 USB po by means o a Field P og ammable Ga e A ay
(FPGA). Communica ions a e bidi ec ional and employ cus om
p o ocols bo h o deli e ing commands o he ASIC and o
eco ding neu al in o ma ion unde di e en channel selec ion
and ope a ion modes. The link is con olled by a use - iendly
p og amming in e ace w i en in C++ which includes a buil -in
ou ine o e ficien ly index and s o e he cap u ed da a. Mesu e-
men s demons a e he sui abili y o he ASIC o cap u ing local
field and ac ion po en ials wi h wo di e en mic oelec ode a ay
pla o ms.
I. INTRODUCTION
In ecen yea s, ad ances in echnology ha e made i
possible o moni o bioelec ic b ain ac i i y using de ices
physically implan ed in he pa ien [1]–[3]. Thanks o he use
o elec ode a ays wi h in e -elec ode sepa a ion in he o de
o ens o mic ons and bandwid hs in he kH ange, such
de ices o e much highe le els o spa io- empo al de ail han
hose achie able wi h elec oencephalog aphy (EEG). This
inc ease in esolu ion is allowing specialis s o p esc ibe mo e
a ea-specific ea men and e en de elop new he apeu ic p o-
cedu es. Implan ed closed loop neu omodula ion sys ems, o
example, can alle ia e he ad e se e ec s o ce ain illnesses,
such as he mo o dys unc ion caused by Pa kinson’s disease,
o p edic and coun e ac epilep ic seizu es [4]. Fu he , e fi-
cien moni o ing o b ain signals om implan ed de ices is
a key ac o in he de elopmen o b ain-machine in e aces
in which app op ia ely ins umen ed objec s can be con olled
exclusi ely by a pe son’s hough s, hus imp o ing he quali y
o li e o pa ien s wi h se e e mobili y impai men s [5].
In his pape , in i o measu emen s ob ained om an im-
plan able 64-channel neu al eco ding sys em p o o ype de el-
oped a IMSE a e p esen ed. The mos salien ea u es o his
p o o ype, as well as i s implemen a ion de ails, we e b iefly
desc ibed in [6]. He ein, a en ion is paid on he bidi ec ional
wi e line in e ace used o communica e he p o o ype wi h
a compu e in o de o configu e he eco ding sys em and
s o e he acqui ed neu al in o ma ion. Al hough he p o o ype
also includes modules o wi eless da a and powe ans e ,
Figu e 1. Mic opho og aph o he mul ichannel neu al eco ding a ay
p o o ype.
in he p esen ed expe imen s, we ha e conside ed a wi eline
app oach as a fi s s ep owa ds assessing he ull unc ionali y
o he p o o ype. Such wi eline in e ace has been implemen ed
by means o a Field P og ammable Ga e A ay (FPGA) and
uses a con en ional 2.0 USB po o communica e wi h he
hos compu e .
Fo he sake o comple eness, a sho e iew o he ab-
ica ed 64-channel neu al eco ding sys em is p esen ed in
Sec ion II and, a e wa d, a desc ip ion o he expe imen al
se up o he in i o measu emen s is gi en in Sec ion III.
Then, he FPGA-based in e ace is desc ibed in Sec ion IV
including de ails o he ASIC p og amming ha dwa e and
he da a eco ding module. Sec ion V p esen s some o he
in i o neu al eco ding measu emen s using animal models
ob ained in he Ins i u e o Bioenginee ing in Elche (Spain).
They consis o local field po en ials (LFPs) cap u ed wi h
a sub-du al mic oelec ode a ay and ac ion po en ials (APs)
eco ded wi h an in aco ical U ah a ay. Finally, Sec ion VI
ends he pape wi h some conclusions.
II. NEURAL RECORDING SYSTEM
Fig. 1 shows a mic opho og aph o he 64-channel neu-
al eco ding sys em, ab ica ed in a 1.2-V 130nm (6M2P)
s anda d CMOS echnology. Each channel comp ises an ana-
log on -end wi h p og ammable gain and unable bandpass
cha ac e is ics o he acquisi ion and condi ioning o neu al
signals; a local SAR-based analog- o-digi al con e e (ADC);
978-1-4799-4242-8/14/$31.00 c
2014 IEEE 486
a digi al module o he de ec ion and comp ession o ac ion
po en ials; and means o empo a ily s o ing he a o emen-
ioned in o ma ion. All hese in-channel unc ions, oge he
wi h an in e nal pad o flip-chip connec ion, a e in eg a ed in
an a ea o 0.16mm2. A dedica ed digi al p ocesso collec s
and classifies he in o ma ion ga he ed by he channels be o e
sending i ou ei he h ough an induc i e link o by means o
a wi eline connec ion, as p esen ed in his pape . Addi ionally,
he p ocesso ans e s pa ame e s o he channels, checks
o digi al consis ency and p o ides in e nal iming e e ences
om a single 4MHz mas e clock. This clock can be ex ac ed
om he ca ie o he induc i e link o , as done in he
p esen ed expe imen s, in oduced h ough a dedica ed pin.
Besides a configu a ion phase in which he di e en chan-
nels a e pa ame ized, he eco ding sys em o e s h ee op-
e a ion modes. In one case, deno ed as calib a ion mode, he
sys em sel -calib a es so ha he eco ding bandwid h o e e y
selec ed channel is uned o he desi ed equency ange and
he gain o hei on -ends is adjus ed o maximally co e he
inpu dynamic ange o he local ADC. The second ope a ion
mode, deno ed as signal acking mode, is in ended o s eam
ou uncomp essed aw da a om he selec ed channels. Finally,
in he las mode, deno ed as ea u e ex ac ion mode, he
digi al comp ession modules o he selec ed channels a e
ac i a ed and he de ec ed APs a e on- he-fly app oxima ed
by piecewise-linea (PWL) ep esen a ions. Fo each selec ed
channel, he AP de ec ion h eshold is adap i ely upda ed
acco ding o he noise floo o he cap u ed signal. In his
mode, a channel emains idle and, hence, i does no ansmi
any in o ma ion, as long as no ac ion po en ial is de ec ed.
The e o e, ac i i y in his mode is e en -d i en hus a o ing
he educ ion o he sys em powe consump ion.
The inpu /ou pu da a ames used o he configu a ion o
he channels and he eco ding o in o ma ion o he di e en
ope a ion modes we e p esen ed in [6].
In his pape , we ha e ocused on he signal acking mode,
unde wo possible eco ding configu a ions:
1) T acking o he whole a ay (64 channels) a a h ough-
pu a e pe channel o 4kS/s. Al hough his configu a-
ion can be also used o de ec he p esence o spikes,
i is mainly used o he eco ding o LFPs a which
he high-pass and low-pass co ne s o he bandpass
cha ac e is ic in e e y channel a e se o he lowes
equencies possible (15Hz and 5.2kHz, espec i ely, in
his p o o ype). I equi ed, he low-pass co ne o he
bandpass cha ac e is ics can be digi ally mo e o -chip
o lowe equencies a e downsampling and FIR fil e -
ing he eco ded s eams. In he epo ed expe imen s,
no ex a fil e ing is applied.
2) T acking pe ow/column (8 channels) a a h oughpu
a e pe channel o 30kS/s. This is he de aul sampling
a e in he AP ea u e ex ac ion mode (bandpass cha ac-
e is ics se be ween 200Hz and 7kHz), bu i can also be
used in acking mode o ully app ecia e he wa e o m
de ails o he eco ded signals. No addi ional o -chip
fil e ing is equi ed.
FPGA
USB Po
Mic oelec ode
a ay
Communica ion
module
Dedica ed
p ocesso
Reco ding
channels
64-channel neu al eco ding ASIC
Figu e 2. Measu emen se up
III. MEASUREMENT SETUP
Fig. 2 shows he schema ic diag am o he measu emen
se up used o in i o neu al eco ding. Two di e en ypes o
mic oelec ode a ays (MEAs) o neu al eco ding we e used.
In one case, a flexible sub-du al mic oelec ode a ay (Mul i
Channel Sys ems MCS GmbH) wi h TiN elec odes sepa a ed
by 300μm (diame e 30μm) placed on a polymide subs a e
was used. The signals cap u ed by he mic oelec odes we e
ans e ed o he 64-channel neu al eco ding sys em by
means o fla ibbon cables connec ed be ween he MEA
adap e (ADPT-FM-36, MCS GmbH) and he ASIC h ough
ow p ecision socke s om Sam ec. In he second case, he
MEA was a U ah a ay wi h an ICS-96 connec o (Black ock
Mic osys ems LLC). A cus om adap e was designed o
a anging he pin dis ibu ions o he ICS-96 connec o (only,
banks A and C) so ha he same connec ion s a egy employed
wi h he flexible MEA could be eused.
A Field P og ammable Ga e A ay (Nexys™2 Spa an-3E
FPGA Boa d by Digilen ) was used o communica e he 64-
channel neu al eco ding ASIC wi h a hos compu e h ough a
con en ional 2.0 USB po . A use in e ace de eloped in C++
was designed o con ol he whole measu emen se up. This
in e ace compiles he Digilen DEPP Dynamic Link Lib a y
[7] o access he USB d i e . The communica ions be ween he
ASIC and he FPGA only need wo downwa d connec ions, o
he command line and w i e enable signals, and one upwa d
connec ion, o he ans e o he neu al in o ma ion eco ded
and p ocessed by he ASIC. Addi ionally, a 4MHz mas e
clock is ans e ed o iming pu poses.
All expe imen al p ocedu es we e pe o med in con o -
mance o he di ec i e 2010/63/EU o he Eu opean Pa liamen
and o he Council, and he RD 53/2013 Spanish egula ion
on he p o ec ion o animals use o scien ific pu poses and
app o ed by he Miguel He nandez Uni e si y Commi ee o
Animal use in Labo a o y. Animal models we e adul male
Long E ans a s.
IV. FPGA INTERFACE
The pu pose o he FPGA boa d is o con ol and ans e he
da a acqui ed by he 64-channel neu al eco ding ASIC. The
FPGA boa d, p og ammed wi h he Xilinx ISE Design Sui e,
implemen s wo majo blocks: (i) a con ol module in cha ge
o sending configu a ion commands o he selec ed channels o
he ASIC and (ii) a da a eco ding module which empo a ily
s o es in in e nal RAMs he da a ecei ed om he ASIC and,
a e wa d, deli e s he in o ma ion h ough he USB po . Bo h
modules make use o a USB in e ace which implemen s he
bidi ec ional communica ion be ween he FPGA boa d and he
USB po . This in e ace consis s o a s a e machine wi h 8-
487
USB In e ace
as b
ds b
db
w
w x_da a
w _ eq
x_da a
x_ d
USB
PC Command
Con olle
ws en_pls
din dou
alid
PISO
24
en DFF
sync en_
Dou
Din
ASIC
clk50M clk4M
F eq. Di ide
clk4M
clk4M
Dou
Din
En_
Figu e 3. Block and iming o he p oposed con olle uni .
bi s bidi ec ional da a bus, fi e con ol signals and one clock
signal (40MHz).
A. Logic Con ol Module
The logic con ol module, shown a he op o Fig. 3, enables
he ex e nal ope a o o configu e he channels o he ASIC,
h ough he Din se ial po , a ins ances o he con ol signal
en_ . As desc ibed in [6], all configu a ion commands s a
wi h a 5-bi s p eamble, ollowed by a payload o 14-bi s and
a 5-bi s o Cyclic Redundancy Check (CRC).
E e y ime he USB in e ace de ec s a w i e eques (w _ eq
is ac i e) om he hos compu e i begins packing bi s in wo d
ames. These ames a e hen ed in o a synch onous pa allel-
inpu se ial-ou pu (PISO) egis e o se ializa ion. Signals
inside he FPGA ha e o be ca e ully synch onized in o de o
a oid ime ou e o s and/o incomple e command ans e s.
To o e come hese issues, an in e nal con olle , clocked a
40MHz, igge s he con ol signal en_ only when he da a
s o ed in he PISO egis e is alid. This con ol signal en_ ,
which defines he da a ans e window o he ASIC, emains
ac i e as long as he con en o he PISO esis e is being
dumped o he ASIC. The 4MHz mas e clock o he ASIC
is de i ed by di iding he 50MHz FPGA clock. The ou pu
s eam o he PISO egis e and he con ol signal en_ a e
aligned o he mas e clock o he ASIC.
The s a -up o he eco ding sys em in ol es h ee com-
mands, as illus a ed in he bo om plo o Fig. 3. The fi s
command is in ended o define he bandpass o he 64 channels
included in he ASIC. Depending on he logic alue o a flag
comp issed in he command s eam, his can be done ei he
by di ec ly defining he p og amming wo ds o he highpass
and lowpass co ne s o he channel’ fil e s o by unning a
sel -calib a ion p ocess o e he whole a ay. In his la e
case, aimed o coun e ac on-chip PVT a ia ions, a uning
mechanism based on digi al equency syn hesis is enabled
o au oma ically adjus ing he a o emen ioned p og amming
wo ds o he desi ed fil e pole alues. The second command
is in ended o calib a e he ol age gain o he channels
o he la ges alue possible, a oiding he sa u a ion o he
embedded da a con e e . Once comple ed his ope a ion, a
hi d command selec s he channels o be eco ded and he
acquisi ion commences.
USB In e ace
as b
ds b
db
w
w x_da a
w _ eq
x_da a
x_ d
USB
PC D
w _da a
W i e Con ol
clk50M clk4M
8
Mem slo #1
Mem slo #2
oggle
d_en
d_
F eq. Di ide
DRead Con ol
d_da a
en_
Dou
Din
ASIC
8
FIFO
RAM
Figu e 4. Block diag am o he da a eco ding module.
B. Da a Reco ding Module
The da a eco ding module, shown in Fig. 4, enables o
ans e he in o ma ion p o ided by he selec ed channels o
he ASIC o a hos compu e . Fo he wo expe imen s unde
signal acking mode desc ibed in Sec. II, ou pu da a ames
coming om he ASIC ha e 85-bi s leng h. They consis o
an 8-bi s p eamble, a 72-bi s in o ma ion packe , and a 5-bi s
CRC checksum. Besides a code o he ope a ion mode (2-
bi s), he in o ma ion packe con ains an iden ifie (6-bi s) o
he column/ ow in he ASIC which is cu en ly ansmi ing
in o ma ion and he digi ized sampled da a sen ou by he
co esponding channels (8-bi s pe channel s eamed om
MSB o LSB). Depending on whe he he iden ifie emains
s a ic o uns cyclically o e he 8 columns/ ows o he a ay,
he ASIC deli e s he eco dings om 8 cells a a h oughpu
a e pe channel o 30kS/s o sweeps he whole a ay a a
h oughpu a e pe channel o 4kS/s.
A w i e con ol uni , synch onized o he 4MHz mas e
clock, iden ifies and al e na i ely dumps he se ial ou pu
ames o he ASIC in o wo memo y slo s which empo a ily
s o e he neu al in o ma ion. E e y ime a new ame is ead
and s o ed, he w i e con ol uni changes he s a e o he
con ol signal, oggle. This same signal is used by a ead con ol
uni , clocked a 50MHz, o e ie e he s o ed in o ma ion om
ha memo y slo which is no unde ead ope a ion. Hence,
while one o he memo ies is being w i en he o he is being
ead, and ice e sa. Because o he di e en clocks used by
he ead and w i e uni s, no in o ma ion is los . Addi ionally,
he ead con ol uni ans e s he e ie ed in o ma ion o a
fi s -inpu fi s -ou pu (FIFO) memo y in pa allel slo s o 8-
bi s. Da a a e ans e ed om his memo y o he USB po
du ing he ime in e als allowed by he p o ocol.
V. IN VIVO RESULTS
Fig. 5 shows 16 o he eco dings cap u ed by he ASIC
when ope a ed in signal acking mode wi h he column scan-
ning op ion enabled (64 channels acked a a h oughpu a e
pe channel o 4kS/s). The flexible sub-du al mic oelec ode
a ay desc ibed in Sec. III was used in his expe imen .
Al hough he expe imen las ed o se e al hou s, only a 10s
in e al is shown in Fig. 5; no subs an ial di e ences we e
app ecia ed in he cou se o he measu emen , no among he
channels. The a e age powe consump ion o he ASIC was
241μWwhich, acco ding o pos -layou simula ions, spli s in o
some 194μW o he eco ding channels and abou 47μW
o he embedded digi al p ocesso and he communica ion
module oge he (see Fig. 2).
488
-500
0
500
-500
0
500
-500
0
500
-500
0
500
-500
0
500
-500
0
500
-500
0
500
-500
0
500
-500
0
500
-500
0
500
-500
0
500
-500
0
500
-500
0
500
-500
0
500
0 1 2 3 4 5 6 7 8 9 10
-500
0
500
Time [s]
0 1 2 3 4 5 6 7 8 9 10
-500
0
500
Time [s]
Figu e 5. LFP ac i i y eco ded om 16 channels in he in- i o es pe o med wi h he neu al eco ding a ay a ached o a flexible a ay o Mul iChannel
Sys ems ( e ical axis in μV).
Fig. 6 shows he 8 eco dings cap u ed by he ASIC when
ope a ed in signal acking mode om a single column o
he channel a ay (8 channels acked a a h oughpu a e
pe channel o 30kS/s). In his case, he U ah a ay was
employed in he in i o measu emen . As can be obse ed
in Fig. 6, isola ed ac ion po en ials and bu s s o spikes a e
clea ly no iceable in he 30ms eco ding. As in he p e ious
case, no subs an ial di e ence om he shown pe o mance
was obse ed along he expe imen . In his case, he a e age
powe consump ion o he ASIC was 69μWwhich spli s in o
some 24μW o he eco ding channels and abou 45μW o
he digi al pe iphe y. I is wo h obse ing no majo di e ence
on he powe consump ion o he digi al ci cui y was de ec ed
as compa ed o he p e ious expe imen . This is because he
lowe numbe o channels is coun e balanced by he highe
da a a e.
VI. CONCLUSIONS
This pape p esen s in i o measu emen s ob ained om
an implan able 64-channel neu al eco ding sys em p o o ype
de eloped a IMSE. De ails a e gi en on he FPGA in e ace
used o communica e he ASIC o a hos compu e . The
implemen ed sys em is capable o acqui ing online da a om
a ious channels o unlimi ed amoun o ime and i is ound
sui able bo h o sub-du al and in aco ical eco dings.
ACKNOWLEDGMENTS
This wo k has been suppo ed by he Spanish Minis y o
Economy and Compe i i eness unde g an TEC2012-33634
and he FEDER P og am.
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-100
0
100
Ch #1 [μV]
-100
0
100
Ch #2 [μV]
-100
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Ch #3 [μV]
-100
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Ch #4 [μV]
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Ch #6 [μV]
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