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A pacemaker powered by an implantable biofuel cell

Cite this: Phys. Chem. Chem. Phys., 2013,
operating under conditions mimicking the human
15, 6278
blood circulatory system – battery not included
Mark Southcott,wa Kevin MacVittie,wb Jan Halámek,*b Lenka Halámková,bc
William D. Jemison,*a Robert Lobeld and Evgeny Katz*b

Received 1st March 2013,
Accepted 6th March 2013
DOI: 10.1039/c3cp50929j
www.rsc.org/pccp
Biocatalytic electrodes made of buckypaper were modified with PQQ-dependent glucose dehydrogenase
on the anode and with laccase on the cathode and were assembled in a flow biofuel cell filled with
serum solution mimicking the human blood circulatory system. The biofuel cell generated an open
circuitry voltage, Voc, of ca. 470 mV and a short circuitry current, Isc, of ca. 5 mA (a current density of
0.83 mA cm2). The power generated by the implantable biofuel cell was used to activate a pacemaker
connected to the cell via a charge pump and a DC–DC converter interface circuit to adjust the voltage
produced by the biofuel cell to the value required by the pacemaker. The voltage–current dependencies
were analyzed for the biofuel cell connected to an Ohmic load and to the electronic loads composed of
the interface circuit, or the power converter, and the pacemaker to study their operation. The correct
pacemaker operation was confirmed using a medical device – an implantable loop recorder. Sustainable
operation of the pacemaker was achieved with the system closely mimicking human physiological
conditions using a single biofuel cell. This first demonstration of the pacemaker activated by the
physiologically produced electrical energy shows promise for future electronic implantable medical
devices powered by electricity harvested from the human body.

1. Introduction were designed and investigated for in vivo electrical power

Implantable devices harvesting energy from biological sources
and based on electrochemical, mechanical and other energy
transducers are currently receiving lots of attention.1–4 Among
biofuel cells5,6 harvesting electrical power from biological
sources and based on the biocatalytic activity of enzymes,7–12
microbial cells13–16 and biological organelles,17 micro-sized
implantable biofuel cells18,19 operating in vivo in a living body
have attracted significant attention in recent research. Biofuel
cells implanted in the retroperitoneal space of a freely moving
rat,20 in the blood vessel in a rabbit ear,21 in the abdomen of an
insect,22 or in the hemolymph of snails,23 clams24 and lobsters25
a
Department of Electrical and Computer Engineering, Clarkson University,
Potsdam, NY 13699, USA. E-mail: wjemison@clarkson.edu
b
Department of Chemistry and Biomolecular Science, Clarkson University, Potsdam,
NY 13699, USA. E-mail: jhalamek@clarkson.edu, ekatz@clarkson.edu
c
Department of Biology, Clarkson University, Potsdam, NY 13699, USA
d
Fletcher Allen Cardiology, University of Vermont College of Medicine,
Medical Center Campus, McClure 1, 111 Colchester Avenue, Burlington,
VT 05401-1473, USA
† M. Southcott and K. MacVittie contributed equally to this work.
generation. In addition to obvious challenges typical for biofuel
cells, such as improving efficiency and operational stability,5,6
problems resulting from the operation in the biological environ-
ment were studied and at least partially resolved.20–25
The energy collected from the body can be utilized to activate
various microelectronic devices. While some microelectronic
devices can work over a fairly broad range of electrical operating
conditions others, such as a pacemaker, require precise voltage
levels and voltage regulation to operate correctly. Thus certain
classes of electronic devices powered by implantable energy
sources will require careful attention to not only energy and
power considerations, but also to voltage scaling and voltage
regulation. This requires appropriate interfacing between
the energy harvesting device and the microelectronic device.
Therefore, another problem appeared when the biofuel cells
were aimed to power electronic devices: achieving the appro-
priate voltage necessary. The voltage produced by the biofuel
cells is thermodynamically limited by the redox potentials of the
chemical species (enzyme redox centers or mediators in the case
of direct26 or mediated electron transfer,27 respectively). Usually
the open circuit voltage generated by biofuel cells based on the

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oxidation of glucose and reduction of oxygen hardly exceeds
0.5 V, being decreased upon consuming current from the cells;5–8
at best the voltage was measured as high as 0.78 V while operating
under non-physiological conditions.28 However, the operational
voltage of modern microelectronics is usually several volts, based
on standard batteries as electrical power supplies.29 The mis-
match between the biofuel cell output voltage and the electronic
devices input voltage was compensated by assembling biofuel
cells in series electrically, thus increasing the total output
voltage,24,30–32 and by collecting produced electrical energy
in capacitors/charge pumps for the burst release in short
pulses.33–36 The first approach, while being successful in
assembling microbial fuel cells in stacks,30–32 has very limited
applicability for the implantable devices since the serial connection
between the opposite poles of individual fuel cells implanted in a
body has a finite resistance associated with the biological tissue
resulting in internal power dissipation and reduced stack voltage.25
In order to solve the problem, single biofuel cells were implanted in
different animals or in separated flow devices mimicking blood
circulation systems and then connected in series.25 This achieved
the desired voltage increase, but had very little hope for future
practical applicability for implantable devices. The second
approach based on electronic interface devices such as charge
pumps and other forms of DC–DC conversion has already been
applied for activating a wireless transmitting electronic device,
however using non-implantable enzyme-based36 or microbial
biofuel cells.33 Application of an interface device to increase
the voltage is rather well-known,37 however it should be
remembered that the voltage increase is achieved at the
expense of the current consumed by the charge pump, thus
putting additional demand on the current output of the biofuel
cell. Implantable micro-size electrical energy generators
connected to an electrical interface can be effectively used for
activating micro-electronic devices operating in the short-
pulses regime, while the time between pulses is used for the
accumulation of energy.38 However, a single implantable bio-
fuel cell connected to a charge pump has never been used for
the continuous powering of an electronic device. The current
produced by the biofuel cell will be particularly important for
the steady-state operation of the load-device rather than short
pulses operation. The present paper demonstrates for the first
time interfacing between an implantable biofuel cell operating
under conditions mimicking human physiology and a continuously
operating pacemaker, while the mismatch between the output
voltage of the biofuel cell and the input voltage of the pacemaker
was compensated by a charge pump and a DC–DC converter
interface circuit.
2. Experimental
2.1 Chemicals
PQQ-dependent glucose dehydrogenase (PQQ-GDH; E.C. 1.1.5.2,
from microorganisms – not specified by the company) was
purchased from Toyobo Co., Japan, and used as supplied. Laccase
(E.C.1.10.3.2, from Trametes versicolor) was obtained from Sigma-
Aldrich and used in experiments after the purification procedure
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described elsewhere.39 1-Pyrenebutanoic acid succinimidyl ester
(PBSE) was purchased from AnaSpec Inc. Serum from a human
male (type AB), 3-(N-morpholino)propanesulfonic acid (MOPS-
buffer) and other standard chemicals were purchased from
Sigma-Aldrich and used as supplied without any further purifica-
tion. Water used in all of the experiments was ultra pure
(18.2 MO cm) from a NANOpure Diamond (Barnstead) source.
2.2 Electrode preparation
Buckypaper composed of compressed multi-walled carbon
nanotubes (Buckeye Composites; NanoTechLabs, Yadkinville,
NC) was used as the electrode material. Electrodes were washed
with isopropyl alcohol with moderate shaking for 15 min at
room temperature prior to their modification. The electrodes
were incubated with PBSE, 10 mM, in ethanol with moderate
shaking for 1 h at room temperature, subsequently rinsed with
ethanol to remove excess PBSE and then with MOPS-buffer
(50 mM, pH 7.0) to remove ethanol. The biocatalytic anodes
were prepared by immobilization of PQQ-GDH: the PBSE-
functionalized electrodes were incubated for 1 hour in the
solution of PQQ-GDH (2.4 mg mL1) in MOPS-buffer (50 mM,
pH 7.0) containing Na2SO4 (100 mM) and CaCl2 (1 mM). The
biocatalytic cathodes were prepared by immobilization of
laccase: the PBSE-functionalized electrodes were incubated
for 1 hour in the solution of laccase (1.5 mg mL1) in potassium
phosphate buffer (10 mM, pH 7.0). The immobilization reactions
proceeded at room temperature with moderate shaking. The
enzyme-modified electrodes were stored (4 1C) in the same buffer
until used in the biofuel cell. Characterization of the enzyme-
modified electrodes (cyclic voltammetry, enzyme content, etc.) was
described in detail elsewhere.23,24
2.3 Biofuel flow cell design and measurements
The flow cell with the dimensions shown in the sketch, Fig. 1,
included the buckypaper electrodes modified with PQQ-GDH
and laccase in the anode and the cathode, respectively, and the
inlet/outlet of the cell were connected to plastic tubes of
0.5 mm internal diameter. A human serum solution with the
glucose concentration of 6.4 mM was pumped (MINIPULS 3,
Gilson) at the volumetric rate of 58.9 mL min1, mimicking
blood flow in a human capillary of 0.008 mm at the linear rate
of 1 mm s1 characteristic of a resting person.40 Note that the
volumetric flow rate was scaled up to generate the same linear
rate in the tube of a bigger diameter. The polarization curve of
the biofuel cell was obtained by measuring voltage–current
Fig. 1 Sketch of the biofuel flow cell.
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Fig. 2 The open pacemaker prior to its wiring to the external power source.
values on the external load variable resistance using a multi-
meter (Meterman 37XR).
2.4 Pacemaker
The pacemaker (Affinity DR 5330L, St. Jude Medical) was
an explanted device that had been removed and discarded
following battery depletion (as per the standard pacemaker
replacement protocol). The metal shell of the pacemaker was
cut and the device was opened, allowing the removal of
the internal battery and the connection of the leads of the
electronic chip to the external biofuel cell, Fig. 2.
2.5 Charge pump and DC–DC converter design
A charge pump and a DC–DC converter were used to amplify
the voltage produced by the biofuel cell to 3 volts, a level
required by the pacemaker. Fig. 3 shows the schematic diagram
of the circuitry. The two primary components are a Seiko S-882z
charge pump and a Seiko S-8353 DC–DC converter. The charge
pump can take an input voltage, VIN, as low as 0.3 volts, and
generate an output of 2 volts. The DC–DC converter further
conditions this signal to the desired output level, VOUT, of
3 volts. Thus the combination of the charge pump and the
DC–DC converter can take a nominal biofuel cell input voltage
range of 0.3–0.5 V and generate the fixed 3 volt output required
Fig. 3 Power converter circuit schematic. Abbreviations used in the circuit shown are standard for electronic circuit annotation.37
6280 Phys. Chem. Chem. Phys., 2013, 15, 6278--6283
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by the pacemaker. The circuit was constructed using a standard
printed circuit board.37
3. Result and discussion
The biocatalytic electrodes based on the buckypaper conducting
support (composed of compressed multi-walled carbon nano-
tubes, CNTs)23–25,39,41–43 with the geometrical area of 6 cm2 were
integrated into a flow cell filled with human serum solution
moving at the flow rate of 58.9 mL min1 with the help of a
peristaltic pump. The human serum solution was spiked with
glucose to the concentration of 6.4 mM to mimic human
physiological conditions. The glucose oxidizing anode was
modified with PQQ-dependent glucose dehydrogenase (PQQ-
GDH) and the oxygen reducing cathode was modified with
laccase. The enzymes were attached to the CNTs with the help
of the bifunctional reagent 1-pyrenebutanoic acid succinimidyl
ester (PBSE) following the published procedure.23–25,39 PQQ-
GDH and laccase enzymes are known for the direct electron
transfer with the electrode support composed of CNTs.44,45
Characterization of the enzyme-modified electrodes (cyclic voltam-
metry, enzyme content, etc.) was described in detail elsewhere.23–25
It should be noted that the electrode size (electrochemically active
area) was increased compared to the previous experiments23–25 to
provide enough current for the operation of the interface circuit
and the connected pacemaker.
The biofuel cell operating under flow conditions was connected
to a variable load resistance and polarization was measured
demonstrating the open circuitry voltage, Voc, ca. 470 mV and short
circuitry current, Isc, ca. 5 mA, Fig. 4 curve a. It should be noted that
the biofuel cell polarization function was measured with the Ohmic
resistance and the derived voltage and current are both functions of
the used resistance. Conversely, the electronic devices – the charge
pump and the connected pacemaker – are not simple Ohmic loads
and they require specific current and voltage for their correct
operation. Measuring the application current demand in order
to predict if a given device will operate with the biofuel cell is an
important step needed for interfacing of biofuel cells and
electronic devices which are powered by them. The current
and voltage demanded by an electronic device are normally
fixed at some point, and a change in the input voltage will cause
the device to work improperly or damage it. The pacemaker
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Fig. 4 Voltage–current dependences of the studied assembly: the polarization curve
of the biofuel cell measured on the variable resistances – voltage and current
produced by the cell as the function of the Ohmic resistance load (a), measured
current consumed by the charge pump–DC–DC interface circuit upon application of
the variable voltage from the external power source demonstrating that the interface
circuit can supply constant current over a wide input voltage range (b), calculated
(eqn (1)) current consumed by the charge pump–DC–DC interface circuit when a
variable voltage is applied and the pacemaker is connected as the load (c). Green
point on the polarization curve and the outcoming arrows show the experimental
operational voltage–current when the biofuel cell is loaded with the charge pump
connected to the pacemaker. The diagram at the top shows the fixed operational
voltage–current parameters in the system.
used in the present study (Affinity DR 5330L, St. Jude Medical)
operates at 3 V and 100 mA peak current draw, measured upon
powering the pacemaker from a power supply with a variable output
(Tenma 72-8700) and registering the pacemaker-generated signals
on an oscilloscope (Agilent DSO-3000).25 Deviating too much from
that input voltage will cause the pacemaker to stop operating, so to
ensure the pacemaker is supplied with the proper voltage, a charge
pump and a DC–DC converter interface circuit were used to amplify
the output voltage of the biofuel cell to match the expected input
voltage of the pacemaker. The process of boosting the voltage to the
level required by the pacemaker comes at a cost of drawing more
current from the fuel cell, since power is conserved (ignoring circuit
efficiency). Two factors must be considered in the analysis of the
operation of the electrical interface, first is the interface current
demand curve without a load (i.e. without the connected pace-
maker). Using a laboratory power supply we varied the voltage
supplied to our charge pump and DC–DC converter interface circuit
and measured the current drawn by the charge pump in order to
obtain a curve of current as a function of applied voltage, Fig. 4,
curve b. The second factor is the efficiency of the charge pump and
DC–DC conversion. The biofuel cell current required for the pace-
maker application was calculated according to eqn (1):
 
Vcp
 Iapp

Vbfc
Ibfc Vbfc ; Vcp ¼ Icp ðVbfc Þ þ (1)
k circuit, (e) the biofuel flow cell with the inlet/outlet connected to a peristaltic
where Ibfc(Vbfc,Vcp) is the biofuel cell current draw as a function
of the voltage of the biofuel cell and the output voltage of the
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interface circuit (Vbfc and Vcp, respectively), Icp(Vbfc) is the
interface circuit current draw as a function of Vbfc, Iapp is
the application device (pacemaker) current draw as seen by
the biofuel cell, and k is the interface circuit’s efficiency defined
as the ratio of the power output and the power input. The Icp
values for the variable voltage applied to the power converter
were measured experimentally (see the text above and Fig. 4,
curve b), while the second term in eqn (1) is an extension of the
ideal transformer current equation,46 with the charge pump
efficiency taken into account. Note that the Vcp value is fixed at
3 V, which is the voltage required by the pacemaker and the Iapp
value should be known for the device being used, in this case
the pacemaker has a peak current draw of ca. 100 mA. These
values are shown in the Fig. 4 inset, and are specific to the
devices used in this study. The efficiency of the power converter
loaded with a pacemaker equivalent resistance was calculated
to be ca. 60%, based on the measured voltage and current
inputs and outputs of the charge pump. The V–I plot derived
from eqn (1) shows the calculated application current demand
curve, Fig. 4, curve c, compared with the measured biofuel cell
polarization curve, Fig. 4, curve a. Because the application
current demand curve lies below the polarization curve we
know that the biofuel cell should be able to power our applica-
tion (the pacemaker). Theoretically, upon connecting to the
pacemaker through the charge pump, the biofuel cell voltage
will drop from Voc to the voltage where the biofuel cell polariza-
tion curve and the load V–I curve first intersect, where it will stay
during operation of the device. The calculated intersection point
was roughly estimated at ca. 400 mV with a current draw of
ca. 1.2 mA. The experimentally determined steady-state operat-
ing point was ca. 300 mV and 2 mA. The difference between the
calculated and experimental operating points is most likely due
to the biofuel cell output varying over the 45 minutes operation
of the charge pump and the pacemaker.
The biofuel cell mimicking an implantable device was
connected to the charge pump and the DC–DC converter inter-
face circuit, which was further connected to a pacemaker medically
used for regulating the heart’s rhythm by administering electrical
charges to the myocardial tissue,47 Fig. 5A. In order to analyze
Fig. 5 (A) Experimental setup which includes (from left to right): (a) a sensor
device for the Medtronic CareLink Programmer, Model 2090, (b) Medtronic
Reveal XT, Model 9529, an implantable loop recorder (ILR), (c) Affinity DR
5330L, St. Jude Medical, a pacemaker, (d) the charge pump–DC–DC interface
pump (not shown in the scheme). (B) Registered pulses generated by the
pacemaker when it is powered by the standard battery. (C) Registered pulses
generated by the pacemaker when it is powered by the biofuel cell.
Phys. Chem. Chem. Phys., 2013, 15, 6278--6283 6281

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Fig. 6 Left: typical shape of the electrical pulse generated by a pacemaker (adapted from ref. 52 with permission). Right: an oscilloscope measuring the electrical
pulses produced by the pacemaker activated using the biofuel cell through the charge pump.
the pacemaker performance, the pacemaker output leads were
connected to the implantable loop recorder (ILR) – a subcuta-
neous electrocardiographic (ECG) monitoring device. This
device is medically used for diagnosis and monitoring of the
heart in patients with recurrent episodes of palpitations or
syncope, for long-term monitoring in patients at risk for or with
documented atrial fibrillation (AF), and for risk stratification in
patients who have sustained a myocardial infarction (MI) and
as well as for those who have certain genetic disorders.48–50 In
the present setup it was used as a medically useful analyzer of
the electrical pulses produced by the pacemaker receiving the
power from the biofuel cell. The loop recorder output was wire-
lessly read using the sensor device of the Medtronic CareLink
Programmer, Model 2090, typically used for the programming of
pacemakers and loop recorders after implantation and for the
remote control of their operation.51 The electrical pulses produced
by the pacemaker and registered by the ILR are very similar when
the pacemaker is powered by a standard battery (WG9438),
Fig. 5B, and by an implantable biofuel cell, Fig. 5C, thus
confirming the correct pacemaker operation while receiving
power from the biofuel cell through the charge pump and the
DC–DC converter interface circuit. In addition to the registration
of the pacemaker-generated pulses with the loop recorder
described above, we analyzed the electrical pulse shape using
an oscilloscope similarly to our previous work.25 The electrical
output cable of the pacemaker was connected to an oscilloscope
(Agilent DSO-3000) for recording the generated electrical pulses.
The obtained pulse shape corresponded to the standard shape
of pulses typical for pacemakers,52,53 Fig. 6. The biofuel cell
produced electrical power which was sufficient for the pace-
maker operation for at least 5 hours (longer stability test was not
performed in this preliminary study).
4. Conclusion
In conclusion we note that the activation of the pacemaker with
the single biofuel cell closely mimicking human physiological
conditions was achieved for the first time. The present result
promises in the future various medical electronic implants
powered by implanted biofuel cells and resulting in bionic
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human–machine hybrids.54 The present study is a step on the
long path to the design of bioelectronic self-powered ‘‘cyborgs’’
which can autonomously operate using power from biological
sources. In the next step of this research, which is underway in
the lab, we will achieve long term operation of the pacemaker
powered by the biofuel cell resulting in the device steady-state
operation without a battery, but harvesting electrical power
from living biological sources.
Acknowledgements
This research was supported by the National Science Foundation
(Award CBET-1066397) and by the Semiconductor Research
Corporation (Award 2008-RJ-1839G). The authors acknowledge
several helpful suggestions from Professor Todd Wey of
Lafayette College.
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