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IEEE SENSORS JOURNAL, VOL. 6, NO.

1, FEBRUARY 2006 187

A Multichannel, Wireless Telemetric Microsystem


for Small Animal Studies
Chung-Chiun Liu, Edward O’Connor, and Kingman P. Strohl

Abstract—Conventional means of collecting biophysiological pa- animals, such as a mouse or rat, are used. Regardless of the
rameters in small animals often involve cumbersome direct wiring sensing elements employed for the biophysical and biochem-
and/or restraint of the animal. At present, there is no system for ical parameters, conventional techniques to transmit the sensor
very small animals that can provide multichannel monitoring of
biopotentials without restraining the animal or small enough in outputs to the external environment involve wire connections
size or light enough in weight for studies with smaller animals. For and restraint tethering which limit the animal movement and
larger animals, such as monkeys or larger rodents, systems have the recording conditions. It will be desirable if the transmis-
been proposed where the transmitter of the system has dimensions sion interface can be accomplished using a wireless telemetric
such as 2 5 2 5 1 3 cm3 and the weight is 9 g; this is far approach. This allows the monitoring of various biological
too high for smaller animals. Also, the battery life of that system
is relatively short ( 10 h). In this study, a multichannel wireless functions of an unrestrained small animal.
telemetric microsystem for biopotential monitoring in small ani- One multichannel telemetry system used a sequential conver-
mals, such as mice or rats, has been designed, fabricated, and eval- sion of the input signals to a current to control a current-con-
uated. This microsystem has four input channels with one calibra- trolled oscillator based upon a monolithic chip [2], [3]. This
tion channel. There are 8 channels on the chip, of which five, the chip (3 3 mm) was complementary bipolar (BJT), and con-
four electroencephalogram (EEG)/electromyogram (EMG) chan-
nels, and the calibration channel, are now in use. The system can tained a single set of amplifiers, reference circuits and a current
also be expanded to more than eight input channels, if desired. In controlled oscillator (CCO). It lacked clocking provisions and
that case, a larger ASIC chip and larger circuit substrate might be required the addition of commercial CMOS chips. Other limi-
required, depending on the type of biopotentials being measured. tations included an inability for providing proper preamplifica-
The amount of ASIC and circuit substrate space consumption is tion, filtering, or input impedance for weak biological signals,
larger for biopotentials such as EEG or EMG than for others such
as temperature or pressure. However, the same clocking-demod- such as EEG or EMG. The overall package size (not including
ulation system could be retained up to 128 channels. The mul- the battery) was large, cm, precluding its use in
tichannel telemetric chip for the present embodiment is approxi- small animals.
mately 2 2 mm, and the overall size of the microsystem is ap- Fryer et al. [4] described a multichannel telemetry system
proximately 10 10 5 mm, including the enclosure package using a time-sharing sequential multiplexing. However, the size
and battery, with a total weight of 1 g. The power consumed by
this four-channel version, where two channels are EEG and two of the system, cm not including the battery, was large
are EMG, is 0.41 mW, and the fabrication process is AMI_ABN. and designed for signals such as strain gauges or electrocar-
There is a magnetic on/off provision. The microsystem has been diogram (EKG) rather than far more difficult to detect signals
used to monitor EEG, Theta activity, and nuchal EMG in mice with such as EEG and EMG. Input impedance was 150 K for EKG.
excellent results. This wireless telemetric microsystem can be ef- Input-referred noise was 20 uV p-p at 50-Hz bandwidth. The
fectively used to record multiple biopotentials from freely moving
small animals. This platform microsystem can be extended to in- current drain was 2.5 mA using two 1.35-V mercury cells.
clude other physiological parameters, such as temperature, pres- The frequency deviation of the FM transmitter was required to
sure, and biological parameters. be trimmed to match the discriminator of a system FM receiver.
Index Terms—Biopotentials, electroencephalogram (EEG), No in vivo EKG recordings were shown.
electromyogram (EMG), multichannel, small animals, wireless Ruedin et al. [5] described a miniaturized EEG transmitter
telemetry. with two asymmetric channels that was anchored to the skull of
a small animal with screws. The size was large,
cm. The input impedance was stated to be 2 10e6 ; for
I. INTRODUCTION
EEG and EMG recordings, this was internally shunted to 6.8

P HYSIOLOGICAL investigation of various biological is-


sues usually requires the collection of biophysical and
biochemical parameters in animal studies. It is often that small
10e4 (68 K) . Other versions of EEG transmitters [6], [7] have
four single-ended rather than differential channels and had the
same construction and size disadvantages as that by Ruedin et
Manuscript received June 29, 2004; revised August 3, 2005. The associate al. [5]. A system reported by Borbely et al. [8] had only a single
editor coordinating the review of this paper and approving it for publication channel.
was Prof. Ralph Etienne-Cummings. An intraperitoneal telemetry device that transmits EEG is
C.-C. Liu and E. O’Connor are with the Department of Chemical Engineering
and the Electronics Design Center, Case Western Reserve University, Cleveland, commercially available. However, this unit has only one EEG
Ohio 44106 USA (e-mail: cxl9@case.edu; exo@cwru.edu). channel and is large, cm in size. The single EEG
K. P. Strohl is with the School of Medicine, Case Western Reserve Univer- channel unit employs a pair of built-in silicone-insulated double
sity and the Louis Stokes VA Hospital, Cleveland, OH 44106 USA (e-mail: kp-
strohl@aol.com). helix stainless steel EEG leads [9], and users cannot connect
Digital Object Identifier 10.1109/JSEN.2005.860358 their own electrodes.
1530-437X/$20.00 © 2005 IEEE

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188 IEEE SENSORS JOURNAL, VOL. 6, NO. 1, FEBRUARY 2006

TABLE I
COMPARISON OF WIRELESS MICROSYSTEM PERFORMANCE

Commercial implantable transmitters to monitor preterm silver-oxide battery. It was mounted with an adhesive material
labor by measuring pressure changes are available [10]. A directly on the back of an insect.
biotelemetry system for EMG and tendon force measurement DeMichele et al. [18] described a 16-channel inductively-
in rats has been proposed [11], as are implantable biotelemetry powered system for neural or EEG signals using an ASIC
transmitters for mice, sensing temperature and pressure, and of .46 .46 cm, fabricated in the AMI ABN process. The
incorporating ion-selective microelectrodes and biosensors overall package size with an enclosure or encapsulation was not
[12]. However, the existing units in this type of devices are specified. It drew 3.8 mA at 4.75 V with a power consumption
fairly large (20 8 mm diameter). of 18 mW. It required gain adjustment. The range of the
A 128-channel EEG monitoring system was described using transmitter was about 3 ft at 385 MHz, with a 1 antenna
time multiplexing with a clock rate of, e.g., 25.6 KHz [13]. This connected to the transmitter. The r.f. bandwidth was specified
system utilized large commercial integrated circuit packages as 15 MHz and the device was tested with a signal consisting of
and discrete parts, and operated via a cable rather than telemetry. a 100-uV 6-Hz square wave, but it was not tested in vivo. The
However, in such applications, a larger chip using the system stated amplifier input-referred noise was high, e.g., 121-uV
described herein could accommodate more channels and enable RMS. Switching noise injected by the scanning process was
such EEG monitoring to be accomplished by telemetry rather found to be a significant problem. The amplifiers demonstrated
than cable. an operating point shift in the presence of r.f. interference
Irazoqui-Pastor et al. [14] described a miniaturized neural or including the VCO.
EEG device, operating at an r.f. carrier frequency of 3.2 GHz Harrison et al. [19] described a neural amplifier built in a
using analog FM. It was inductively powered and a 100-W Ham 1.5- m CMOS process (AMI_ABN), with six amplifiers on a
radio transmitter driving a large external coil with a passive 2.2 2.2 mm chip. The amplifier was designed with MOSFETs
impedance matching circuit was required. It was approximately and on-chip capacitors. The supply voltage was 5-V split-supply
cm and required a 2.5-cm monopole transmitting and it had a frequency range for use with neural electrodes
antenna. The power consumption was approximately 5.8 mW. from millihertz to 7 KHz. The measured input-referred noise
It appeared to be single channel. The input-referred noise of the was 14-uV p-p. The RMS was 2.2 uV; this would lead to a
OTA portion of the design was 8 uV, but the crest factor ([15, crest factor of 3.8 [15, p. 299]. The neural amplifier was re-
p. 299]) was not stated. designed for low-frequency biosignal applications such as EEG
Mohseni et et al. [16] described a wireless neural mi- or brain-surface electrodes, to exhibit a bandwidth of below 1 to
crosystem with three signal channels and a marker channel 30 Hz. It was stated that the input-referred noise voltage for the
operating with FM in the 88–108 FM band. The marker EEG version was 1.6-uV RMS. There was a neural waveform
channel was used for sequencing the channels in the system’s recording but there was no in vivo EEG recording presented in
demultiplexer. The size of the microsystem was 1.8 1.3 cm this study.
without the two 1.5-V batteries. The power consumption was Table I summarizes the results of our telemetry system and
2.44 mW. The input-referred noise was 7.5-uV RMS but those of five others referenced in this paper. The input-referred
the crest factor was not stated. The device had not been tested noise, power dissipation, detectable signal, and transmission
in vivo. The dc offset of the input signals was over a range of range, as well as the parameters of telemetry link frequency,
0.25 V. The ASIC used the AMI ABN process but required number of data channels, power supply, system clock frequency,
laser trimming, both to set clocking rate and to control the communication scheme, number of external components, total
amount of frequency modulation. weight, and package dimensions are presented. Our system
Takeuchi et al. [17] described a hybrid neural device which shows the lowest input-referred noise, and our system has the
used commercial parts. It was a single channel and operated lowest power dissipation of a complete telemetry system. By
with an 80–90 MHz FM r.f. carrier. It was tested with a 500-uV comparison, our system has a small footprint. The telemetry link
test signal. The dimensions were relatively large, 1.5 0.8 cm, frequency of our system is higher than those of [16] and [17],
not including any powering system. The power consumption but lower than those of [14] and [18]. Our system has more data
of this device was 10 mW. It operated for only 30 min with a channels with the exception of [18]; in that system, a much larger

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LIU et al.: MULTICHANNEL, WIRELESS TELEMETRIC MICROSYSTEM 189

ASIC chip is used. Table I also provides information on the total


weight (where provided by the investigators) and the power
requirements of the systems cited, and our system compared
favorably in these aspects. The communication scheme of our
system is amplitude-modulation-based (on–off keying) while
those of the other complete telemetry systems are FM-based;
this use of an FM-based system is apparently associated with
higher power dissipation. The power supply voltage of our
system also compares well with other systems.
The advance in microfabrication techniques as well as micro-
electronics in recent years provides an opportunity to develop
microsize, wireless telemetric interface suitable for small an-
imal monitoring. Sensors for physiological parameters include
those for common parameters such as EEG, EMG, EKG, pres-
sure, temperature, and also for various chemical and biochem-
ical parameters. Thus, a wireless telemetric interface needs to Fig. 1. Transmitter package (ca. 1 2 1 2 0 5 cm).
:

be capable of transmitting these types of sensor outputs.


EEG refers to recording graphically the electric activity of II. DESIGN AND FABRICATION OF THE
the brain, particularly the cerebral cortex, by means of exter- INTERFACE MICROSYSTEM
nally placed electrodes. The frequency range is 0.5–100 Hz.
Theta EEG refers to a recording from the temporal region, In our laboratory, a low-power 2 2 mm integrated circuit
having a frequency range of 4–7 Hz. Problems associated signal processor chip was developed and applied to a transmitter
with recording EEG are low signal levels and high 50–60 Hz package as shown in Fig. 1, that could be anchored to the head
power line interference. EMG refers to recording the electrical of a small animal such as a rat or mouse. The dimensions of
impulses that pass through a muscle as it contracts and relaxes. the transmitter including the enclosure package and battery are
EKG refers to recording electrical impulses as they vary during approximately cm. The vertical space for the circuitry
the cardiac (heart) cycle. in the circuit compartment of the package is about 1.1 mm.
In this study, we had developed a multichannel (four channels The input signals of the bipolar (differential) EEG or EMG
with a calibration channel) wireless telemetric microsystem for channels modulated the period of a sub-carrier oscillator and
EEG and EMG monitoring for small animals. Specifically, this the time-multiplexed sub-carrier oscillator output was converted
microsystem was used for the study of sleep disorders using to pulses, which gated a wireless transmitter on and off. The
mice as the animal model. From the physiological viewpoint, wireless transmitter was an r.f. oscillator with a tank coil as the
sleep apnea is initiated and sustained by instability in the transmitting antenna. The pulsed RF output from the tank coil
respiratory control system [20]. Short-term potentiation of or other antenna structure was then picked up by a radio re-
ventilation (STP), also called “ventilatory after-discharge,” ceiver, which drove a demodulator to reconstruct the individual
is evoked by brief hypoxia, promotes ventilatory stability, input signals and output them to a PC with waveform acquisi-
and protects against dysrhythmic breathing or posthypoxic tion software.
frequency and ventilatory decline [21]. An absence of STP The digital clocking on the chip provided for up to eight mul-
promotes the appearance of repetitive apneas, as supported by tiplexed channels; four signal channels plus a fifth on-chip cal-
studies on patients with obstructive sleep hypo-apnea syndrome ibration channel. The purpose of the calibration channel was to
(OSAHS) [22] or congestive heart failure (CHF) patients produce a reference output the amplitude of which corresponded
with Cheyne-Stokes respiration (CSR) [23]. Hence, ventilatory to an EEG or EMG input level of 50-uV p-p. It also served as
instability and periodicity are common to CSR, OSAHS, and an error detector in that it indicated by its frequency, waveshape
the appearance of periodic breathing at altitude [24]. Central and output channel that the signal was properly received by the
and obstructive apneas may occur in the same patient over a radio receiver and processed by the demodulator.
night [25]. These studies indicated that posthypoxic behavior For animal study chronically implanted brain or muscle elec-
and periodicity are fundamental features in the pathophysiology trodes were connected to the transmitter and used to record
of sleep apnea syndromes. spontaneous or evoked brain potentials (EEG) and neck muscle
The complexity of understanding the pathophysiology of activity (EMG). The package itself could be anchored to the
sleep disorder would require the investigation of certain organs skull with cranioplastic cement or fitted with pins for insertion
such as the brain involved in both central chemosensory and into a small socket mounted on the animal’s head.
coordination of chemical and nonchemical reflexes. Such inves- The details of this multichannel wireless telemetric mi-
tigation would need to monitor the EEG and EMG developed crosystem are given in the following sections.
from a small animal model. It would be important that the
animal is not restrained during this study. Thus, it is mean- A. Technology
ingful to have a multichannel wireless microsystem capable A 1.5- 2-metal 2-poly CMOS process with an NPN op-
of monitoring EEG and EMG that can be used in studies with tion, which can operate at 3 V, was used to implement an in-
unrestrained small animals. tegrated circuit chip providing the main part of the circuitry for

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190 IEEE SENSORS JOURNAL, VOL. 6, NO. 1, FEBRUARY 2006

Fig. 2. Block diagram of the ASIC.

the telemetry transmitter package. This fabrication process al- signal. There was also CMOS clocking circuitry, a block of
lows p-channel and n-channel enhancement mode MOSFETs, monostable multivibrators with outputs combined by gating to
bipolar NPNs and other electronic structures such as resistors, provide output pulses and synchronization pulses, and a power
capacitors and diodes to be integrated. This process, AMI ABN toggle-on/toggle-off switch circuit.
[16], [18], [19], and [26], is applicable to low-noise analog de- The power switch was toggled by an external magnetic sensor
signs or mixed-signal designs. such as a Hall-effect sensor or a reed switch turning the trans-
mitter on and off with a magnet. The Hall-effect sensor was
B. Process Characteristics an SMT having a footprint of mm and was incorpo-
Resistors can be fabricated from n-wells in this process. Poly1 rated onto the circuit substrate of the hybrid package along with
and poly2 can be used to form on-chip capacitors. Diodes may the ASIC and the bare-die BJT r.f. oscillator/transmitter chip.
be laid out for the bonding pads for ESD protection. Guard A reed switch selected from currently-available types would
rings may be laid out for signal isolation between circuit blocks have required a slightly larger overall package. The Hall-effect
and for latch up prevention. An NPN option can be used for sensor, a pole-independent device with a latched digital output,
BiCMOS digital speed-up purposes and was used for analog worked by producing an output which went high to low as a
purposes in this application. small magnet was brought near and went low to high again when
it was withdrawn, thus toggling the chip supply voltage via the
C. Circuit Considerations on-ASIC power switch circuit mentioned above. The on–off cir-
This CMOS process having an NPN option [26] was used so cuitry of the ASIC does not have significant static power con-
that along with the digital clocking circuitry, the bipolar devices sumption; the Hall-effect sensor, an Allegro A3212 ELHLT, has
could be used to provide a higher transconductance, a better a static power consumption of 15 uW. The manufacturer’s data
matching, lower offsets and lower flicker noise for the analog sheet is numbered as Allegro Microsystems 27 622.61G.
EEG and EMG amplifiers that were needed for the application. The set of four selectable amplifier stages converted the input
A block diagram of the ASIC chip is shown in Fig. 2. The cir- EEG or EMG signals into linearly proportional output currents,
cuit was designed with 4 input differential preamplifiers, four which, along with a reference current from the calibration cir-
selectable second-stage amplifiers that could activate sequen- cuit, were fed into the current controlled subcarrier oscillator.
tially from pulse inputs from the clocking circuitry, and a cur- These currents were fed in sequence so that the channels were
rent-controlled subcarrier oscillator. The gain of each selectable time-division multiplexed. A diagram describing the encoding
second-stage amplifier was a function of the pulse current of the scheme is shown in Fig. 3. Each channel was turned on for two
select pulse for that channel. The gain of each input differential complete cycles of the subcarrier oscillator; a half-cycle on each
preamplifier stage was fixed. Between each input differential end of this period served to provide setup time, and one sub-
preamplifier stage and the associated selectable second-stage carrier oscillator cycle was used for the data measurement of
amplifier was a pair of capacitors (indicated between dashed an input channel or for the calibration signal. Each channel’s
lines), of which one coupled the signal and the other provided value was encoded in the duration between RF pulses, i.e., the
roll-off to the band of signal frequencies. As previously indi- subcarrier oscillator’s period was modulated by the channel’s
cated there was a calibration circuit for producing a reference value. An increase in input current to the subcarrier oscillator

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LIU et al.: MULTICHANNEL, WIRELESS TELEMETRIC MICROSYSTEM 191

Fig. 3. Encoding scheme diagram.

Fig. 4. Timing and reference/calibration signals diagram.

resulted in a shortening of the period. If the subcarrier oscil- onto one of the multiplexed channels. A timing and reference
lator is operated at 10–15 kHz it will produce a minimum sam- signals diagram is shown in Fig. 4.
pling frequency per channel of 625 Hz and a Nyquist frequency Simulated waveforms at circuit nodes are shown in Figs. 5–7.
of 312 Hz, which exceeds the 100-Hz bandwidth which is re- Fig. 5 simulates the output of an input channel amplifier-pream-
quired for the EEG and EMG signals in this application. The plifier pair, having an input signal of 70 Hz at 5 000-uV p-p am-
CMOS timing circuit was a chain of toggle-connected master- plitude. The second amplifier is gated on and off by the select
slave D-type flip-flops, some of which drove a 1-of-8 logic de- pulse input for that channel. In this simulation, the select pulse
coder block. Three more input channels could have been used is actually a SPICE pulse rather than an SCO clock pulse; the
with the 1-of-8 decoder arrangement, but the physical space was period of the SCO clock would actually be varying. The output
not available on the 2 2 mm chip to accommodate the input current is 70 uA p-p. Fig. 6 simulates the select pulse (with pe-
amplifiers for the three extra channels. Additional toggle-con- riod held constant for simplification purposes) for the channel.
nected D flip-flops divided down the clock signal from the sub- The amplitude is 3 V, the on time is 162 uS and the frame time is
carrier oscillator to about 6 Hz, which was used to drive the 1296 uS. Fig. 7 simulates the frequency response of the channel
calibration circuit and inject a square wave as a reference signal for a differential signal input level of 50 uV p-p.

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192 IEEE SENSORS JOURNAL, VOL. 6, NO. 1, FEBRUARY 2006

Fig. 5. Simulation of output of signal channel stage.

Fig. 6. Simulation of channel amplifier select pulse.

Fig. 7. Simulation of channel amplifier frequency response.

Separate parts of the block diagram are shown in Figs. 8–11. the magnitudes of the current sources are controlled by an ex-
They are the input preamplifier, Fig. 8, the subcarrier oscillator ternal current, e.g., the current from a signal channel amplifier
(SCO), Fig. 9, the divide-by-128 section (DFFs 5–11), Fig. 10, or from the calibration section. A latching circuit is formed from
and the monostable multivibrators block, Fig. 11. In the SCO, two 2-input CMOS NAND gates. The positive feedback around

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LIU et al.: MULTICHANNEL, WIRELESS TELEMETRIC MICROSYSTEM 193

Fig. 8. Signal channel input preamplifier stage diagram.

Fig. 9. SCO block diagram.

Fig. 10. DFFs 5–11 (divide-by-128) block diagram.

the loop is used to ensure that only one of the MOS transis- tery compartment of the enclosure package, above the circuit
tors is on at a time. The switching points of the comparators compartment. The battery was located inside of the wireless
combined with the current source determine the oscillator fre- transmitter coil, which was wound around the outside of the
quency of the SCO. Two 22-pF timing capacitors were required enclosure package of the transmitter unit.
for the SCO and they were implemented by very small 0402 or The battery was an Li/MnO2 watch cell with a nominal
0201 external chip capacitors, which were mm or voltage of 3 V and an average capacity of 30 mAh to 2.0 V.
smaller. The divide-by-128 chain of toggle-connected CMOS The volume of the battery is 0.2 cm . It is specified by the
DFFs 5–11 provides a low frequency for the calibration signal. manufacturer that if the load is such that the current drain is
In the Monostable Multivibrators block, each one-shot consists 64 uA and the operation is 24/7 the time to cutoff voltage (2.0
of a 2-input CMOS NOR gate, a CMOS inverter, an on-chip ca- V) is 467 h. The wireless transmitter drew 40 uA and the Hall
pacitor, and an on-chip resistor. The trigger input of a one-shot sensor drew 12 uA; the ASIC drew 93 uA. The current drain
can be longer than the output pulse width. of the telemetry hybrid transmitter including ASIC, wireless
The power for the chip and transmitter unit was supplied transmitter and Hall-effect sensor was 145 uA, and, thus, this
from a CR1025 3-V watch cell which was located in the bat- system could operate for 168 h (7 days, 24/7) or longer. It was

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194 IEEE SENSORS JOURNAL, VOL. 6, NO. 1, FEBRUARY 2006

Fig. 11. Monostable multivibrators block.

found by measurement that the CR1025 dropped below 3 to


2.9 V within a few hours; it then gradually reached 2.83 V
and remained at this level during most of its lifetime. When
it reached the end of its lifetime it then dropped within a few
hours, to 2.0 V. The effective supply voltage of the ASIC and
hybrid transmitter was, thus, approximately 2.83 V.
The power consumption of the entire hybrid transmitter was
0.41 mW. This was considerably less than that of other multi-
plexed or wireless designs referred to above.
This device, like most battery-operated devices, was subject
to the effects of battery drop and parameters were expected to
change somewhat during operational life of the battery as a re-
sult. Such changes, as, e.g., changes in channel gains, were small
due to the use of on-chip voltage regulators and the use of cur-
rent mirrors tending to act as current regulators. However, it was
found that the change in signal amplitude was tracked by the
change in calibration waveform amplitude over the range of 3.2
to 2.7 V. The amplitude change for both signal output wave- Fig. 12. Microphoto of ASIC chip (ca. 2.2 2 2.2 mm).
form and calibration channel output square-wave amplitude was
2.0% per 0.1-V change in battery voltage over the range of 3.0 ASIC because of considerations of space and flexibility in re-
to 2.7 V. Thus, the amplitude change throughout the operational gard to the wireless link, as well as to avoid any problems which
life of the battery was small but would be correctible by refer- might arise from having an RF generating circuit directly on
encing the demodulator’s signal-channel gain to the calibration the ASIC in close proximity to analog circuitry which was pro-
square-wave amplitude. cessing low-level signals such as EEG and EMG. A micropho-
The conductive substrate in epi wafers can have currents in- tograph of the ASIC processor chip of the telemetry system is
duced into it by the magnetic field of a (spiral) on-chip inductor, shown in Fig. 12.
and this inductor-induced noise through the substrate can affect The block diagram of the ASIC chip was shown previously in
other circuits on the same chip [27]. Although our device did not Fig. 2. The input stages utilized dc blocking capacitors of very
utilize an on-chip inductor, the integrated circuit chip used was small physical size (0402 and 0603) on the hybrid substrate in
within the field of an inductor. No degradation of performance such a way that capacitive dc blocking, a standard precaution
was observed in the miniaturized unit in comparison to larger with EEG amplifiers, was implemented.
prototypes with the coil remote from the chip. The input impedance of the input preamplifier stages was re-
lated to circuit parameters and represented a tradeoff between
D. Circuit Implementation stage current drain, electronic flicker noise and chip size. The
The ASIC constituted the processor section of the complete measured input impedance was 670 K and was found to be
telemetry link. The only requirements to complete the imple- adequate for the EEG and EMG signals of the application; how-
mentation of the telemetry function of the transmitter were a ever, in future versions, this impedance may be increased to
single external bare-die BJT chip, a resistor and a capacitor on 3.8 M as indicated below. The in vivo electrode-tissue inter-
the hybrid substrate, plus a tank circuit. The resistor could have face impedances of the animal electrodes used in the in vivo
been included on the ASIC but it was put instead on the cir- system testing were relatively low. Information about the an-
cuit substrate so that it would be physically closer to the wire- imal electrodes used is given later in this paper.
less oscillator section and, thus, tend to better decouple RF from In a test, the result of loading (reducing the input impedance)
the ASIC. The transistor and capacitor were not laid out on the of standard Grass EEG amplifiers was examined for in vivo

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LIU et al.: MULTICHANNEL, WIRELESS TELEMETRIC MICROSYSTEM 195

mouse EMG and EEG at 300 K resistive shunt impedance. be replaced by a current source to further increase the CMRR
In vivo EMG signals were not influenced by the 300-K shunt in future versions. The output node of the input preamplifier
across the input terminals of the Grass amplifier. The in vivo stage EXT1, drove filter capacitors C1 and C2, connected to
EEG signals were not significantly attenuated (less than 3 dB nodes EXT2 and EXT3 of the following stage. The purpose of
below 5 Hz) by the 300-K shunt. The higher frequency C1 and C2 was to set the high and low frequency roll-offs as
components were not noticeably attenuated. The equivalent narrow as possible, to pass only the spectrum required, since
electrode impedance appeared to increase as the frequency the greater the amplifier bandwidth the greater the output noise
decreases; however, the signals appeared entirely usable even and input-referred noise [15, p. 125]. Essentially, C1 of Fig. 8
at 300 K. may be regarded as coupling the signal to the associated se-
It is of interest that earlier, transistorized commercial and re- lectable second-stage amplifier (not shown in Fig. 8 but indi-
search EEG equipment utilized lower input impedances than the cated in Fig. 2) while C2 may be regarded as providing roll-off
value mentioned above; in [5], cited above, the input impedance to the band of signal frequencies. These capacitors, indicated
was stated to be approximately 2 10e6 ; however, for EEG in Fig. 8 as being separated from the amplifier circuitry by a
and EMG recordings, this was stated by the authors to be inter- dashed line, are also indicated (between a pair of dashed lines)
nally shunted to only 6.8 10e4 (68 K) . in Fig. 2, and separated from the input differential preamplifier
Noise is considered to be a dominant factor in EEG equip- stage by the first of the dashed lines.
ment, particularly in CMOS input amplifiers [14], [16], [18], The input-referred noise of the EEG channels, from trans-
and [19] where the electronic (circuit-generated) noise, such as mitter channel input to system demodulator output, was found
flicker noise, is often too high. In EEG equipment, both the RMS by measurements and calculation [15, p. 275] to be 0.69 uV
and the crest factor [15, p. 299] should be stated in equipment RMS with a crest factor [15, p. 299] of 3.84 at 100-Hz BW,
specifications but frequently are not. and 0.36-uV RMS with a crest factor of 3.69 at 30-Hz BW.
In this development, BJTs were used for input stages of the The input-referred noise of the EMG channels was found to be
EEG/EMG telemeter because the flicker noise of MOSFETs is 0.63-uV RMS with a crest factor of 3.84 at 100-Hz BW.
known to be as much as 10 to 1000 times larger [15, p. 123] Thus, the EEG signal processing in this system exhibited less
unless space-and-power-consuming techniques are used. noise than the systems using CMOS circuitry for signal pream-
In a BJT, the total equivalent input noise is plification [14], [16], [18], and [19].

E. Wireless Transmitter
The train of output pulses from the ASIC, which processed
the input EEG and EMG signals and converted the signals to
a pulse format, was applied to the input resistor R1 of an r.f.
oscillator used as a wireless transmitter, as shown in Fig. 13.
Also It was an Armstrong oscillator in which the collector winding
coil L1 and the tank circuit winding coil L2 of the transformer
were combined into an autotransformer single tapped tank coil
L, serving as the transmitting antenna of the telemetry system
where ; and having a tuning capacitor C1 across it. Coupling capacitor
; ; C2 provided feedback to the base of Q1. Capacitor C3 placed the
; tap point at r.f. ground. Resistor R1 provided base current and
' ; set the forward bias on Q1 when the output pulses of the ASIC
; were present, thereby causing a burst of r.f. oscillation during
; each ASIC output pulse. The circuit operated class C during
: : the intervals when it was gated on by the output pulses of the
. The above equation for Eni^2 [15, ASIC. Because of the flow of r.f. current in L, an r.f. electromag-
pp. 142–143] is valid for a 1-Hz bandwidth at the frequency f. netic field was generated by the coil; this r.f. field then served to
Increasing the transistor quiescent collector current increases propagate the wireless signal. The use of crystal control was not
the 1/f noise [15, p. 126]. As the collector current drops, elec- found necessary. Because the transistor and coupling capacitor
tronic 1/f noise of the stage may be expected to decrease, while were not incorporated on the ASIC, any r.f generating circuit
small-signal input impedance rises. The CMRR of long-tailed which can be on–off keyed, using any carrier frequency or any
pair Q1, Q2 in Fig. 8 increases as emitter resistor R7 is in- antenna type, of sufficiently small footprint, might be substi-
creased. Thus, because collector current drops but CMRR in- tuted in this system.
creases as R7 increases, R7 was made as large as space on the
chip permitted. Because R1 and R2 shunt the input impedance F. Demodulator
of the stage, they were also both made as large as space per- The train of transmitter pulses from the output of the radio
mitted. The resulting input impedance was 670 K but simula- receiver was applied to the input of the demodulator of the
tion showed that the unshunted input impedance was 4 M . system, a block diagram of which is shown in Fig. 14. An
R1 and R2 may, thus, be replaced in future versions by current LED was turned on by a pulse-sensing circuit to indicate signal
sources to increase the channel input impedance. R7 may also reception from the transmitter. These pulses were applied to

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196 IEEE SENSORS JOURNAL, VOL. 6, NO. 1, FEBRUARY 2006

mismatch on the chip was trimmed out in the demodulator as


the system was calibrated channel-by-channel with a 50-uV
p-p signal being applied to the channel input of the hybrid
transmitter containing the particular ASIC and the channel was
trimmed for a 1.0-V p-p output signal from the corresponding
output of the demodulator unit being calibrated for that specific
transmitter. In the future, the use of a different BiCMOS type
of process in which p-n-p’s as well as n-p-n’s are available
may allow closer on-chip matching between channels, by
using BJTs to replace less-well-matched MOSFETs in analog
circuitry, thus allowing for less need for trimming.

G. Radio Receiver
Fig. 13. Wireless transmitter circuit diagram.
The output of the system’s oscillator/transmitter was sensed
using a small antenna such as a half-dipole or loop, which fed a
a pulse separator circuit which separated the active interval, single-conversion receiver, a block diagram of which is shown
or signal channel pulses, from the synchronization, or marker in Fig. 15. The receiver incorporated a front end, an i.f. section
pulses which were also sent by the transmitter, so that the and a second detector. A commercial front end having a tuning
demodulator was able to sequence the channels. When the range of 50–810 MHz in four bands was used in this receiver.
marker and signal interval pulses were separated, the signal An internal switch was used to select the correct band for re-
interval pulses were applied to the clock input of a flip-flop; ceiving the transmitter. The i.f. bandwidth of this receiver was
a pulse at the beginning of a signal channel interval set the adjusted to correspond to the spectral content of the transmitter
flip-flop output high and the pulse at the end of the channel pulses while rejecting external interference; the i.f. circuitry was
interval reset the flip-flop output low. Thus, a series of pulses broadly-tuned and the bandwidth was in the range of 2 MHz.
were generated at the output of the flip-flop, whose high levels The receiver gain was limited by the adjustment of the front-end
corresponded in duration to the signal channel intervals. These and IF gains, to suppress interference of extraneous signals and
high levels were then used to gate a clock input of a counter noise with the transmitter pulses. The second detector circuit in
in such a way that when the flip-flop output pulses were high this receiver produced a pulse output, which corresponded to
the counter up-counted, and when the flip-flop pulses went the pulse output of the transmitter’s ASIC chip, which on–off
low, the up-counter stopped counting. At the end of each signal keyed the transmitter unit’s wireless transmitter circuit. The re-
channel interval of the transmitter, a binary (digital) output was, ceiver second detector’s pulse output was fed to the demodu-
thus, generated. This digital output was applied to a D-to-A lator unit, to be processed in order to recover the transmitter
converter, which converted the digital to an analog voltage, channel interval and marker signals, and subsequently the EEG
corresponding to the EEG or EMG signal sample, and held this or EMG input signal information. The system’s receiver also in-
sample until the next frame of signal channel intervals. The corporated an audio section, which produced an audible signal
up-counter was then reset and at the start of the next signal to facilitate tuning the receiver to the transmitter signal. The RF
channel interval the process started again. There were eight receiver is not a commercial one and it, therefore, has no manu-
D-to-As, corresponding to eight channels, of which four were facturer information or data sheet reference; however, the front
used for signals, one was used for the calibration signal and end is a Zenith 175-00 014 CATV tuner made by Zenith Elec-
three of which were reserved for future ASIC versions. At the tronics Corporation, Glenview, IL.
end of each frame of eight channels, the flip-flop mentioned
above was reset by the marker pulses from the pulse-separation H. Miniature Enclosure for Telemetry Transmitter
circuit mentioned previously. The output of each D/A was The miniature enclosure for the telemetry transmitter was
then passed through a dc amplifier/filter to eliminate the D/A a micromachined box that could be made of alumina ceramic
increment-noise and calibrate the signal level so that 1 V p-p or macor ceramic. A microphotograph of the box is shown in
output from the demodulator corresponded to 50-uV p-p input Fig. 1. A cover slid in low-friction micromachined grooves, and
to the transmitter. The output of each amplifier/filter was then served to clamp the battery against the internal battery contacts
passed through an additional low-pass filter to limit channel as well as to hold the battery. The battery shelf also acted as
bandwidth to 100 Hz, for the purpose of reducing electronic the top of the circuitry compartment, which was only 1.1 mm
flicker noise [15, pp. 19-20]. The amplified and filtered signal in height. The enclosure box was set on the circuit substrate,
was then passed through a dc block and a buffer to eliminate which carried the ASIC chip, a SMT Hall-effect sensor, an R.F.
dc offset. In addition, because the subcarrier oscillator of the oscillator chip BJT, and the various chip capacitors and a chip
transmitter was current-to-frequency-modulated, a 1/f converter resistor; the .22- and .001-uF chip capacitors and the chip re-
was added between the low-pass filter and the dc blocking filter sistor were 0402 or 0201 size and some of the remaining chip
in the four signal channels. Although eight channels were capacitors were 0603 size. The ASIC chip and the chip BJT were
sent from the transmitter, only four signal channels and one connected to the circuit substrate with wire bonds. Flip-chip at-
calibration channel were used, so that there were five output tachment could also have been used. A photograph of the com-
amplifier/filter/buffer circuits in the demodulator. Any channel plete multichannel wireless telemetry circuitry on the alumina

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LIU et al.: MULTICHANNEL, WIRELESS TELEMETRIC MICROSYSTEM 197

Fig. 14. System demodulator block diagram.

Fig. 15. System radio receiver block diagram.

TABLE II
TABLE OF OFF-CHIP COMPONENTS OF THE TRANSMITTER

gauge was wound around the top of the enclosure, leaving clear-
ance for the sliding cover. The assembly was held together by
a cement. Leads from the electrodes implanted in the animal,
Fig. 16. Microphoto of transmitter hybrid substrate (ca. 1 2 1 cm). or from a connector on which the box might be mounted, were
brought to the side or bottom terminals. The replacement of
substrate is shown in Fig. 16. The size of this circuit substrate the battery was relatively simple by sliding the top cover of the
was cm and was smaller than the footprint of a U.S. miniature enclosure to access the battery.
dime. It may be assembled manually or by automated methods. A list of the off-chip components of the hybrid substrate
A transmitting coil of a few turns of wire of approximately #40 and enclosure package is shown in Table II. These off-chip

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198 IEEE SENSORS JOURNAL, VOL. 6, NO. 1, FEBRUARY 2006

Fig. 17. B6 Mouse recording (active) made with ASIC system.

Fig. 18. B6 Mouse recording (slow wave) made with ASIC system.

components are annotated as to the components shown in the mice. Two C57BL/6J and two A/J mice (Jackson Laboratory,
schematics included in this paper. Bar Harbor, ME) were implanted with stainless steel electrodes
for the recording of the cortical and theta EEGs and of the EMGs
of the nuchal (neck) muscles. A midline incision was made to
III. RESULTS AND DISCUSSIONS
expose the skull and neck muscles posterior to the skull. Two
After the ASIC chip was fabricated and the hybrid trans- pairs of stainless steel wires 0.21 mm in diameter and stripped
mitter was built, the in vivo performance of this system was for 0.5 mm at the ends were surgically placed to contact the dura
assessed by recording the EEG and EMG waveforms of small for bipolar theta and cortical EEG recordings. Two other pairs of

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LIU et al.: MULTICHANNEL, WIRELESS TELEMETRIC MICROSYSTEM 199

Fig. 19. AJ Mouse recording (REM) made with ASIC system.

Fig. 20. B6 Mouse recording (slow arousal) made with ASIC system.

stainless steel electrodes made by knotting stainless steel wires A data analysis program was used to view the demodulated
and stripping the knotted portion were sutured into the surface EEG and EMG data via an analog conditioning filter/amplifier
of the neck muscle for bipolar EMG recordings. (CWE, Inc.) and a 12-bit Data Acquisition System (National In-
The electrodes were connected to the telemetry transmitter struments PCI-MIO-16E) or 16-bit PCI-6033E DAQ. The Data
and the animal was placed in a Lucite chamber (10 cm in di- Acquisition System (DAS) was used in a LabView environment
ameter and 6 cm high) with bedding and food and water. Each on a P-III desktop computer. The resultant data was sampled
animal was studied for three days. at 512 Hz and stored on a hard disk. Records were scored for

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200 IEEE SENSORS JOURNAL, VOL. 6, NO. 1, FEBRUARY 2006

TABLE III of 50–60 Hz power line interference, often a problem with EEG
TABLE OF SPECIFICATIONS OF THIS SYSTEM systems, was not observed. The system channel crosstalk effects
were visually absent, since clearly evidence of the calibration
square wave was not seen in the signal channels, or vice versa,
and evidence of the EEG waveforms was not seen in the EMG
or calibration channels, or vice versa.
The calibration signal served an important purpose in the
recordings in that it indicated at all times during the recordings,
by continuously providing a waveform of known wave-shape,
frequency, and amplitude, that the system was working and that
r.f. transmission and reception were being properly achieved. It
indicated also that demodulation was properly accomplished,
and all channels including signal channels were being displayed
in their proper positions on the recording. In other systems
there has often been no indicator to assure that transmission
was being adequately accomplished or that channels were
being properly demodulated or output in proper sequence,
so that, for example, what might have seemed to be EEG
might have been not a true EEG waveform but possibly only
a system artifact. The calibration channel, thus, served the
purpose of an error detector in the recordings as well as an
amplitude reference.
In the recorded waveforms, the noise levels represented
the resultant of all noise sources, including digital, 50–60 Hz
power line interference, and ambient r.f. interference as well as
electronic system noise such as flicker, shot and thermal. There
was good signal integrity as compared with, e.g., recordings
made directly with Grass amplifiers, despite these noise sources
and despite changes in light and temperature as well during
the in vivo recording experiment. The measured EEG channel
electronic noise parameters at 30-Hz BW have been previously
stated in this paper to be 0.36-uV RMS with a crest factor
of 3.69, and at 100-Hz BW to be 0.69 uV with a crest factor
of 3.84. This was the overall system noise from the channel
input of the hybrid transmitter to the channel output of the
sleep stage, i.e., assignment was made of the kind of waveform system demodulator. It is evident that this noise is considerably
as, e.g., “Waking,” “Slow-Wave,” or “REM.” less than that of the amplifier alone at 30-Hz BW in [18]
For each mouse, several segments of data, each about 5 h above, which is an all-CMOS design in the same process [26].
long, were recorded. The data was then analyzed. Example In the future, however, the use of another BiCMOS type of
waveforms telemetered by the telemetry system are shown. chip process where both polarities of BJTs are available, may
Each recording has visible at the left the labels EEG, Theta, allow still further reduction in noise to be achieved, by using
EMG1, EMG2, CAL. Each recording also has vertical bars BJTs to replace noisier MOSFETs in the analog circuitry.
in the center that are labeled to show the signal level corre- Specifications of the system are indicated in Table III. A com-
sponding to the height of the bar. parison of this wireless microsystem with other wireless mi-
Fig. 17 shows cortical EEG, Theta activity and nuchal EMG crosystems is shown in Table I, above. In Table III, the parameter
from a B6 mouse in active wakefulness. Fig. 18 shows the EEG, RF BW is measured on the bench by tuning a calibrated com-
Theta and EMG from a B6 mouse in slow wave sleep. Fig. 19 mercial telemetry receiver between the points where the signal
shows a set of waveforms from a B6 mouse in slow wave sleep reception from the telemetry transmitter drops off. The commer-
with arousal from sleep. Fig. 20 shows signals from an AJ cial receiver has switchable bandpass filters with bandwidths
mouse in REM sleep. The calibration signal, a square wave of suitable for television testing purposes, e.g., several megahertz.
5–6 Hz, is shown on the bottom channel of each recording.
The bandwidth used for the cortical EEG and the EMG was
IV. CONCLUSION
100 Hz. The bandwidth used for the theta EEG was reduced
by the recording instrumentation to improve the display of the We have designed and tested a multichannel wireless
characteristics of this waveform parameter. telemetry system for up to four biopotential signals plus a
By referring to the waveform recordings, which represented calibration channel for use in the monitoring of small animals
the entire system as well as the ASIC and hybrid transmitter, it (mouse or rat). It is expandable to more channels. The system
could be seen that system CMRR was sufficient so that the effect has a package size of approximately cm (including

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LIU et al.: MULTICHANNEL, WIRELESS TELEMETRIC MICROSYSTEM 201

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[3] S. J. Gschwend, J. W. Knutti, H. V. Allen, and J. D. Meindl, “A general- Dept. Elect. Electron. Eng., The Hong Kong University of Science and
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Chung-Chiun Liu is the Wallace R. Persons Pro-
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selective recording from 5 out of 12 chronically implanted electrodes,” in
Professor of chemical engineering at Case Western
Proc. Biotelemetry II. 2nd Int. Symp., Davos, Basel, Switzerland, 1974, Reserve University, Cleveland, OH, where he is
pp. 182–184. also the Director of the Center for Micro and Nano
[7] W. Kraft and F. Voegeli, “4-Kanal Miniatursender zur Uebertragung Processing. His research areas include chemical and
des Elektroencephalogramms von Kleintieren,” AGEN-Mitteilungen, biological sensors and sensor arrays, applications
vol. 15, pp. 19–24, 1973. of microfabrication to the development of chemical
[8] A. A. Borbely, I. Baumann, and N. M. Waser, “Multi-channel telemetry and biological microsystems, wireless telemetric
of physiological parameters (body temperature, ECG,EEG) in the rat. interface technology, and microelectrochemical en-
II. Applications in neuropharmacology,” Kimmich and Vos Biotelemetry, ergy sources, including microfuel cells and printable
pp. 381–388, 1972. batteries. He has authored 190 journal publications and holds 12 U.S. patents.

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202 IEEE SENSORS JOURNAL, VOL. 6, NO. 1, FEBRUARY 2006

Edward O’Connor is a Technical Specialist in elec- Kingman P. Strohl received the B.S. in anthro-
tronics at the Center for Micro and Nano Processing, pology from Yale University, New Haven, CT, in
Case Western Reserve University, Cleveland, OH, a 1970, the M.D. degree from Northwestern Uni-
post which he has held for the past 31 years. He has versity, Evanston, IL, in 1974, and he completed
been working in the areas of biomedical electronics his training in internal medicine at the University
and radio frequency telemetry. He has attended of Kentucky, Lexington, in 1977, and a research
the Case Institute of Technology where he studied fellowship in respiratory physiology and pulmonary
electrical engineering and has published his work in medicine at Peter Bent Brigham Hospital, Harvard
biotelemetry. He holds four U.S. patents. School of Health, Cambridge, MA, in 1980.
Since 1980, he has been with Case Western Re-
serve University, Cleveland, OH, and is now a Pro-
fessor of medicine, anatomy, and oncology at the School of Medicine. The
themes advanced in funded research over this period of time include the me-
chanical properties of the upper airway (1981 to 1988), biomarkers of hypoxia
(1988 to 1997), and generic features of breathing and sleep (1997 to present),
all relevant to clinical disorders of sleep apnea.

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