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Biofuel powered glucose detection in bodily fluids with an n-type conjugated polymer

Nature Materials volume 19, pages 456–463 (2020)Cite this article

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Abstract

A promising class of materials for applications that rely on electron transfer for signal generation are the n-type semiconducting polymers. Here we demonstrate the integration of an n-type conjugated polymer with a redox enzyme for the autonomous detection of glucose and power generation from bodily fluids. The reversible, mediator-free, miniaturized glucose sensor is an enzyme-coupled organic electrochemical transistor with a detection range of six orders of magnitude. This n-type polymer is also used as an anode and paired with a polymeric cathode in an enzymatic fuel cell to convert the chemical energy of glucose and oxygen into electrical power. The all-polymer biofuel cell shows a performance that scales with the glucose content in the solution and a stability that exceeds 30 days. Moreover, at physiologically relevant glucose concentrations and from fluids such as human saliva, it generates enough power to operate an organic electrochemical transistor, thus contributes to the technological advancement of self-powered micrometre-scale sensors and actuators that run on metabolites produced in the body.

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Fig. 1: Glucose sensing with an n-type accumulation mode OECT.
Fig. 2: As the enzyme catalyses glucose, the n-type polymer becomes doped as if it is electrochemically addressed.
Fig. 3: Biosensor performance at different operating conditions and in the presence of endogenous species.
Fig. 4: The performance of the all-polymer biofuel cell.
Fig. 5: Performance of the EFC as a self-powered sensor and as a circuit component.

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All the data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials. Additional data related to this paper may be requested from the authors.

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Acknowledgements

The authors thank E. Bihar (KAUST) for her guidance during the experiments with saliva samples. The authors also thank J. Surgailis, J. I. de Oliveira Filho, L. B. Ospina and T. Cecilia-Hidalgo (KAUST) for spontaneous help. D.O., I.M. and S.I. gratefully acknowledge financial support from the KAUST Office of Sponsored Research (OSR) under Award no. OSR-2016-CRG5-3003. G.N. and S.I. acknowledge support from KAUST Sensors Initiative OSR Award no. REP/1/2719. Figures 1a and 4a were created by H. Hwang, scientific illustrator at KAUST.

Author information

Author notes

  1. Tamilarasan Palanisamy

    Present address: Electrodics and Electrocatalysis Division (EEC), CSIR-Central Electrochemical Research Institute (CSIR-CECRI), Karaikudi, India

  2. These authors contributed equally: David Ohayon, Georgios Nikiforidis.

Authors and Affiliations

  1. Biological and Environmental Science and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia

    David Ohayon, Georgios Nikiforidis, Achilleas Savva, Shofarul Wustoni & Sahika Inal

  2. Physical Science and Engineering Division, KAUST, Thuwal, Saudi Arabia

    Andrea Giugni, Tamilarasan Palanisamy, Xingxing Chen, Enzo Di Fabrizio, Pedro M. F. J. Costa & Iain McCulloch

  3. Department of Chemistry and Centre for Plastic Electronics, Imperial College London, London, UK

    Iuliana Petruta Maria & Iain McCulloch

  4. KAUST Solar Center, KAUST, Thuwal, Saudi Arabia

    Iain McCulloch

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Contributions

S.I. conceived the research, designed the experiments and supervised the work. D.O, G.N. and A.S performed the OECT and biofuel cell experiments. D.O. fabricated the devices and performed the UV–vis–near infrared studies. S.W. designed the electropolymerization experiments. X.C, I.P.M. and I.M. provided the n-type materials. P. M. F. J. C. and T.P. helped with the biofuel cell experiments. A.S. and D.O. performed the QCM-D experiments. A.G. performed and E.D.F supervised the Raman spectroscopy measurements. D.O. and G.N. wrote the manuscript with S.I. All the authors were involved in the discussion and participated in manuscript input.

Corresponding author

Correspondence to Sahika Inal.

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A US provisional application (no. 62/770934) related to this work was filed by S.I. and D.O.

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Extended data

Extended Data Fig. 1 Real-time response of the OECT channel current to varying concentrations of glucose in the measurement solution.

The concentration of glucose that is introduced to the solution increases incrementally from 10 nM to 100 μM, followed by a stepwise decrease back to 10 nM. In the end, glucose is washed away by a rinsing step. When the P-90 film is incubated with GOx, the enzyme adsorbs on P-90 without prior surface treatment because of the glycol-rich regions of the surface.

Extended Data Fig. 2 Real-time response of the OECT to successive amounts of H2O2.

H2O2 was added as molar equivalent of the glucose solutions used in the sensing experiments. Arrows indicate the addition of the H2O2 aliquots with concentrations of 10 nM, 50 nM, 100 nM, 500 nM, 1 µM, 5 µM, 10 µM, 25 µM, 50 µM, 100 µM, 250 µM, 500 µM, 750 µM, 1 mM, 2.5 mM, 5 mM, 7.5 mM, 10 mM, 12 mM, 15 mM and 20 mM. An increase in drain current is observed only with 20 mM of H2O2. Once the current stabilizes, the biosensor is rinsed with fresh buffer solution (‘Rinse’). The OECT shows a negligible response to H2O2 (only 1.3 nA increase) and requires long stabilization time, compared to changes induced by the enzymatic reaction. See Supplementary Fig. 5 for possible reactions that take place on P-90/GOx surface.

Extended Data Fig. 3 Spectroscopic investigations on P-90/GOx system.

(a) UV-VIS spectrum of a P-90/GOx film in PBS before and after the addition of glucose (1 mM). The film is subject to a constant doping potential at 0.5 V vs Ag/AgCl during the course of the experiments. (b) UV-VIS spectrum of a P-90/GOx film measured in PBS with and without the addition of 1 mM of H2O2. (c) Raman spectrum of a P-90 film subject to increasing doping potentials, from 0 to +1 V vs Ag/AgCl. After 1 V, the film was de-doped by applying 0 V vs Ag/AgCl. (d) Raman spectra of a P-90 film and P-90/GOx film. Inset shows the magnified spectral region between 1390 and 1730 cm−1 and the main peak attributions. In the spectrum, the region between 1100 and 1800 cm−1 refers to the resonant region of the backbone, while the low energy region ( < 1100 cm−1) is associated with the side-chains. See Supporting Information for further discussion.

Extended Data Fig. 4 Oxygen reduction reaction (ORR) activity of p(EDOT-co-EDOTOH).

(a) Chronoamperometry of the p(EDOT-co-EDOTOH) cathode under various atmospheres. The gases were introduced by bubbling the solution for 30 minutes. Afterwards, the gas tubing was held above the solution to shield it from the outside atmosphere. The measurement was performed at 0 V vs. VOC. (b) Cyclic voltammogram of p(EDOT-co-EDOTOH) cathode recorded in air (blue) and in O2 saturated buffer (red) under a rotating disk electrode. Scan rate is 10 mV.s−1 and rotation rate is 10 Hz (600 rpm). Arrow indicates the scan direction. (c) Reciprocal of current density of p(EDOT-co-EDOTOH) as a function of the rotation speed. The number of electrons (n) involved in the ORR is extracted from the slope of each curve and at a specific potential of the voltammogram. At low negative potentials (≤−0.375 V) the system follows a 4 e− direct reduction of oxygen to water. See Supporting Information for further discussion.

Extended Data Fig. 5 Electrochemical characterization of the biofuel cell.

(a) Extended cyclic voltammogram of the EFC comprising a P-90/GOx anode and a p(EDOT-co-EDOTOH) cathode, fuelled by 1 mM of glucose in PBS. Scan rate is 5 mV.s−1 and the arrow indicates the scan direction. The dotted lines depict the onset potential for the reduction and oxidation reactions. The difference between the onset potentials gives the theoretical open circuit voltage of the cell12. Inset shows the magnified region of the voltammogram until 0.6 V. (b) Half-cell open circuit potentials of the P-90/GOx anode and p(EDOT-co-EDOTOH) cathode in PBS. Glucose concentration is 1 mM. Triplicate experiments were performed for each sample while the open circuit stabilization time was ~2 hours.

Extended Data Fig. 6 Power output of the fuel cell when the anode is P-90 (no GOx) or P-90 functionalized with GOx (P-90/GOx).

All measurements were performed in PBS (pH 7.2) and in the absence of glucose. The EFC comprised a Nafion membrane.

Extended Data Fig. 7 The figure of merit for the membrane-free, all-polymer biofuel cell.

(a) Dependence of cell voltage (red circles) and power (green squares) on current density of the EFC fed with 10 mM of glucose solution. The measurements were acquired with an external resistor (1 kΩ - 10 MΩ). (b) OCV and MPD dependence on glucose concentration. (c) Comparison of the MPD of EFCs prepared with and without a Nafion membrane as a function of glucose concentration. The error bars show the standard deviation of the mean value of OCV and MPD values for three independent measurements.

Extended Data Fig. 8 The performance of a membrane-free EFC comprising an electrochemically doped P-90.

The P-90 film is functionalized with GOx and placed in PBS as the working electrode of a three-electrode system where a Pt coil is the counter electrode and Ag/AgCl is the reference electrode. The P-90 electrode is doped at –0.6 V vs Ag/AgCl and is also connected to the p(EDOT-co-EDOTOH) cathode. The power output of this EFC is markedly higher than the pristine EFC in the presence of 1 mM glucose, determined using an external resistor (1 kΩ - 10 MΩ).

Extended Data Fig. 9 Enzymatic biofuel cells power an accumulation mode OECT.

The VG and VD are supplied by the fuel cells with an output voltage of −0.15 V and −0.07 V, respectively. The OECT was switched ON and OFF by reversing the polarity of the gate voltage (by swapping the anode/cathode of the fuel cell connected to the gate electrode). The EFCs are fed with a constant concentration of aqueous glucose as fuel. The equivalent electrical circuit is presented on the right-hand side. The figure demonstrates the real-time changes in the source-drain current of a fully EFC powered accumulation mode OECT (based on a p-type organic semiconducting channel)42 as we reverse the polarity of the EFC biasing the gate electrode.

Supplementary information

Supplementary Information

Supplementary Tables 1–3, Figs. 1–15, Discussion and References.

Supplementary Video 1

Biofuel cell with a membrane supplies power to light up an LED.

Supplementary Video 2

Membrane-free biofuel cell supplies power to light up an LED.

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Ohayon, D., Nikiforidis, G., Savva, A. et al. Biofuel powered glucose detection in bodily fluids with an n-type conjugated polymer. Nat. Mater. 19, 456–463 (2020). https://doi.org/10.1038/s41563-019-0556-4

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