Printable transistors for wearable sweat sensing

Human performance monitoring (HPM) devices for sweat sensing in both civilian and military uses necessitate chemical sensors with low limits of detection, rapid read out times, and ultra-low volumes. Electronic and electrochemical sensing mechanisms for biomarker identification and quantification are attractive for overall ease of use, including robust, portable, fast readout, and simple operation. Transistors have the high signal gain required to sense low concentrations (μM to pM) at low volumes (μL to nL) in real-time (<1 minute), metrics not achievable by benchtop analytical techniques. Two main challenges currently prohibit the realization of transistor-based biosensors: i) the need for printed devices for low-cost, disposable sensors; and ii) the need to overcome diminished sensitivity in high ionic strength solutions. In this proof-of-concept work, we demonstrate organic electrochemical transistors (OECT) as a promising low cost, printable device platform for electrochemical detection of biomarkers in high ionic strength environments. This work focuses on how the materials choice and functionality impacts the electrochemical and sensor and transducer performance and determining the feasibility of reducing the size of the sensor to nanoliter volume detection. Initial studies target dopamine. Detection limits for simple electrochemical approaches using platinum or glassy carbon electrodes remain relatively high (~ 1-10 ng/mL or 50 nM). Using an OECT, we demonstrate an initial detection level of dopamine at ~ 10 pg/mL achieved without any selective binding modifications to the gate electrode at gate voltages below 1 V.

[1]  J. V. Spiegel,et al.  The extended gate chemically sensitive field effect transistor as multi-species microprobe☆ , 1983 .

[2]  S. Ingebrandt,et al.  Time-dependent observation of individual cellular binding events to field-effect transistors. , 2009, Biosensors & bioelectronics.

[3]  P. Willner Dopamine and depression: A review of recent evidence. II. Theoretical approaches , 1983, Brain Research Reviews.

[4]  A. Kussak,et al.  Determination of dopamine and serotonin in human urine samples utilizing microextraction online with liquid chromatography/electrospray tandem mass spectrometry. , 2007, Journal of separation science.

[5]  N. T. Son,et al.  Conjugated Polyelectrolyte Blends for Electrochromic and Electrochemical Transistor Devices , 2015 .

[6]  J. Bergquist,et al.  Catecholaminergic suppression of immunocompetent cells. , 1998, Immunology today.

[7]  Jonathan Rivnay,et al.  Benchmarking organic mixed conductors for transistors , 2017, Nature Communications.

[8]  George G. Malliaras,et al.  Steady‐State and Transient Behavior of Organic Electrochemical Transistors , 2007 .

[9]  R. Šlamberová,et al.  Monitoring of dopamine and its metabolites in brain microdialysates: method combining freeze-drying with liquid chromatography-tandem mass spectrometry. , 2011, Journal of chromatography. A.

[10]  B. Everitt,et al.  Dopamine receptors in the learning, memory and drug reward circuitry. , 2009, Seminars in cell & developmental biology.

[11]  C. Lluis,et al.  The emergence of neurotransmitters as immune modulators. , 2007, Trends in immunology.

[12]  Graeme Eisenhofer,et al.  Catecholamine Metabolism: A Contemporary View with Implications for Physiology and Medicine , 2004, Pharmacological Reviews.

[13]  C. Altar,et al.  In Vivo Assessment of Dopamine and Norepinephrine Release in Rat Neocortex: Gas Chromatography‐Mass Spectrometry Measurement of 3‐Methoxytyramine and Normetanephrine , 1987, Journal of neurochemistry.

[14]  C. Su,et al.  Ultrasensitive detection of dopamine using a polysilicon nanowire field-effect transistor. , 2008, Chemical communications.

[15]  Amay J. Bandodkar,et al.  Wearable Chemical Sensors: Present Challenges and Future Prospects , 2016 .

[16]  Itamar Willner,et al.  Analysis of dopamine and tyrosinase activity on ion-sensitive field-effect transistor (ISFET) devices. , 2007, Chemistry.

[17]  M. Schöning,et al.  Recent advances in biologically sensitive field-effect transistors (BioFETs). , 2002, The Analyst.

[18]  Johannes C. Brendel,et al.  A High Transconductance Accumulation Mode Electrochemical Transistor , 2014, Advanced materials.

[19]  Chi On Chui,et al.  On the origin of enhanced sensitivity in nanoscale FET-based biosensors , 2014, Proceedings of the National Academy of Sciences.

[20]  Francesco Amenta,et al.  Dopamine and vascular dynamics control: present status and future perspectives. , 2011, Current neurovascular research.

[21]  S. Udenfriend,et al.  Measurement of human dopamine-beta-hydroxylase in serum by homologous radioimmunoassay. , 1975, Proceedings of the National Academy of Sciences of the United States of America.

[22]  H. Sirén,et al.  Determination of dopamine and methoxycatecholamines in patient urine by liquid chromatography with electrochemical detection and by capillary electrophoresis coupled with spectrophotometry and mass spectrometry. , 2003, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[23]  Chi On Chui,et al.  Optimization of the Sensitivity of FET-Based Biosensors via Biasing and Surface Charge Engineering , 2012, IEEE Transactions on Electron Devices.

[24]  V. Camp,et al.  Melanoma detection by enzyme-radioimmunoassay of L-dopa, dopamine, and 3-O-methyldopamine in urine. , 1981, Clinical chemistry.

[25]  Xianjie Liu,et al.  An Organic Mixed Ion–Electron Conductor for Power Electronics , 2015, Advanced science.

[26]  Francesca Fanelli,et al.  Adenosine A2A-Dopamine D2 Receptor-Receptor Heteromerization , 2003, Journal of Biological Chemistry.

[27]  C. Heidbreder,et al.  Selective dopamine D3 receptor antagonists enhance cortical acetylcholine levels measured with high-performance liquid chromatography/tandem mass spectrometry without anti-cholinesterases , 2006, Journal of Neuroscience Methods.

[28]  Oh Seok Kwon,et al.  Human dopamine receptor nanovesicles for gate-potential modulators in high-performance field-effect transistor biosensors , 2014, Scientific Reports.

[29]  Matti Kaisti,et al.  Detection principles of biological and chemical FET sensors. , 2017, Biosensors & bioelectronics.

[30]  R. Ebstein,et al.  A radioimmunoassay of human circulatory dopamine-β-hydroxylase☆ , 1973 .

[31]  Andrew H. Miller,et al.  Psychoneuroimmunology Meets Neuropsychopharmacology: Translational Implications of the Impact of Inflammation on Behavior , 2012, Neuropsychopharmacology.

[32]  V. S. Lin,et al.  Molecular recognition inside of multifunctionalized mesoporous silicas: toward selective fluorescence detection of dopamine and glucosamine. , 2001, Journal of the American Chemical Society.

[33]  A. Björklund,et al.  Fluorescence histochemical and microspectrofluorometric mapping of dopamine and noradrenaline cell groups in the rat diencephalon. , 1973, Brain research.

[34]  Christopher J. Tassone,et al.  Structural control of mixed ionic and electronic transport in conducting polymers , 2016, Nature Communications.

[35]  Jürgen Westermann,et al.  Simple, rapid and sensitive determination of epinephrine and norepinephrine in urine and plasma by non-competitive enzyme immunoassay, compared with HPLC method. , 2002, Clinical laboratory.

[36]  Richard S. Nicholson,et al.  Theory and Application of Cyclic Voltammetry for Measurement of Electrode Reaction Kinetics. , 1965 .

[37]  R. Ebstein,et al.  A radioimmunoassay of human circulatory dopamine-beta-hydroxylase. , 1973, Life sciences.

[38]  S. Udenfriend,et al.  Photometric assay of dopamine- -hydroxylase activity in human blood. , 1972, Clinical chemistry.

[39]  Bernard P. Puc,et al.  An integrated semiconductor device enabling non-optical genome sequencing , 2011, Nature.

[40]  Christian Bénar,et al.  Organic Electrochemical Transistors for Clinical Applications , 2015, Advanced healthcare materials.

[41]  Piet Bergveld,et al.  Possibilities and limitations of direct detection of protein charges by means of an immunological field-effect transistor , 1990 .

[42]  Tai Hyun Park,et al.  Dopamine Receptor D1 Agonism and Antagonism Using a Field-Effect Transistor Assay. , 2017, ACS nano.

[43]  Syed A Hashsham,et al.  Miniaturized nucleic acid amplification systems for rapid and point-of-care diagnostics: a review. , 2012, Analytica chimica acta.

[44]  P. Willner Dopamine and depression: A review of recent evidence. I. Empirical studies , 1983, Brain Research Reviews.

[45]  George G. Malliaras,et al.  Controlling the mode of operation of organic transistors through side-chain engineering , 2016, Proceedings of the National Academy of Sciences.

[46]  Po-Hung Yang,et al.  CMOS Open-Gate Ion-Sensitive Field-Effect Transistors for Ultrasensitive Dopamine Detection , 2010, IEEE Transactions on Electron Devices.

[47]  G. Fink,et al.  Concentrations of dopamine and noradrenaline in hypophysial portal blood in the sheep and the rat. , 1989, The Journal of endocrinology.

[48]  J. D. Neill,et al.  Dopamine levels in hypophysial stalk blood in the rat are sufficient to inhibit prolactin secretion in vivo. , 1978, Endocrinology.

[49]  L. Geffen,et al.  Radioimmunoassay and Clearance of Circulating Dopamine‐β‐Hydroxylase , 1972, Circulation research.

[50]  Kalpana Besar,et al.  Electrochemical processes and mechanistic aspects of field-effect sensors for biomolecules. , 2015, Journal of materials chemistry. C.

[51]  G. Haegeman,et al.  Resistance of the dopamine D4 receptor to agonist-induced internalization and degradation. , 2010, Cellular signalling.