Transistor in a tube: A route to three-dimensional bioelectronics

Pitsalidis, Charalampos; Ferro, Magali; Iandolo, Donata; Tzounis, Lazaros; Inal, Sahika; Owens, Róisı́n M.

doi:10.1126/sciadv.aat4253

Cited by 80 publications

(107 citation statements)

References 47 publications

(61 reference statements)

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“…As such, this inherently sensitive transducer has been used in many biological applications as a platform for transducing and amplifying biological signals (typically ionic) to electronic readouts. A few examples include, sensing of bioanalytes (i.e., metabolites, DNA, and so forth), neural signals recordings as well as in vitro toxicology testing (Curto et al, ; A. M. Pappa et al, ; Pitsalidis et al, ; Spyropoulos, Gelinas, & Khodagholy, ).…”

Section: Introductionmentioning

confidence: 99%

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A highly sensitive molecular structural probe applied to in situ biosensing of metabolites using PEDOT:PSS

Pappa²,

Pitsalidis³

et al. 2019

Biotech & Bioengineering

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A large amount of research within organic biosensors is dominated by organic electrochemical transistors (OECTs) that use conducting polymers such as poly(3,4‐ethylene dioxythiophene) doped with poly(styrenesulfonate) (PEDOT:PSS). Despite the recent advances in OECT‐based biosensors, the sensing is solely reliant on the amperometric detection of the bioanalytes. This is typically accompanied by large undesirable parasitic electrical signals from the electroactive components in the electrolyte. Herein, we present the use of in situ resonance Raman spectroscopy to probe subtle molecular structural changes of PEDOT:PSS associated with its doping level. We demonstrate how such doping level changes of PEDOT:PSS can be used, for the first time, on operational OECTs for sensitive and selective metabolite sensing while simultaneously performing amperometric detection of the analyte. We test the sensitivity by molecularly sensing a lowest glucose concentration of 0.02 mM in phosphate‐buffered saline solution. By changing the electrolyte to cell culture media, the selectivity of in situ resonance Raman spectroscopy is emphasized as it remains unaffected by other electroactive components in the electrolyte. The application of this molecular structural probe highlights the importance of developing biosensing probes that benefit from high sensitivity of the material's structural and electrical properties while being complimentary with the electronic methods of detection.

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Section: Introductionmentioning

confidence: 99%

“…A few examples include, sensing of bioanalytes (i.e., metabolites, DNA, and so forth), neural signals recordings as well as in vitro toxicology testing (Curto et al, 2017;A. M. Pappa et al, 2016Pitsalidis et al, 2018;Spyropoulos, Gelinas, & Khodagholy, 2019).…”

mentioning

confidence: 99%

A highly sensitive molecular structural probe applied to in situ biosensing of metabolites using PEDOT:PSS

Pappa²,

Pitsalidis³

et al. 2019

Biotech & Bioengineering

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“…For this reason, these devices have entered successfully the fields of biosensors and bioelectronics, unfolding their innovative potential in biomolecules detection, electrophysiology, in vitro and in vivo cellular recordings . Currently, intensive research effort is focused on novel OECT channel materials and architectures to gain faster response time, increased sensitivity, and lower power consumption targeting new applications in wearable technology and health care . Despite their well‐established relevance in the development of novel biotechnologies, the device physics still lacks a comprehensive understanding.…”

Section: Introductionmentioning

confidence: 99%

Microscopic Determination of Carrier Density and Mobility in Working Organic Electrochemical Transistors

Mariani

Conzuelo

Cramer

et al. 2019

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voltages. For this reason, these devices have entered successfully the fields of biosensors and bioelectronics, unfolding their innovative potential in biomolecules detection, [2][3][4][5] electrophysiology, [6][7][8] in vitro and in vivo cellular recordings. [9][10][11] Currently, intensive research effort is focused on novel OECT channel materials [12] and architectures [13] to gain faster response time, increased sensitivity, and lower power consumption targeting new applications in wearable technology and health care. [14][15][16][17][18] Despite their well-established relevance in the development of novel biotechnologies, the device physics still lacks a comprehensive understanding. Operational models able to accurately define and interpret the device working principle are required, as they would reveal well-aimed strategies for metrics refinement and guide targeted optimization of novel materials. Therefore, an improved knowledge of OECTs operation would impact on applications requiring higher sensitivity and amplification of the output signal, fast response time as well as selectivity.In a typical OECT configuration, an organic film deposited between two metal electrodes, that is, source (grounded) and drain collectors, and a gate electrode are in contact with the same electrolyte solution. The organic material constituting the transistor channel is usually poly(3,4-ethylenedioxythioph ene):poly(styrene sulfonate) (PEDOT:PSS), that is, a polyelectrolyte complex containing a degenerately p-doped semiconductor (PEDOT) and a polyelectrolyte counterion (PSS). The presence of multiple phases in thin films of PEDOT:PSS at the nanoscale has been revealed by scanning probe microscopy. Pancake-shaped PEDOT-rich islands are separated by lamellas of PSS-rich domains, thus forming a blend of electronic and ionic phases. [19] Mixed ionic and electronic transport is crucial in OECT operation and originates from the reversible doping/ dedoping mechanism of the organic film. It is well known that doping and dedoping of conjugated polymers like PEDOT rely on reversible electrochemical redox processes (oxidation and reduction, respectively). [20] Electrochemical doping is the phenomenon that rules OECTs operation and is driven by the applied potential between the polymer in the channel and the gate material. Concurrently, cations from the electrolyte are needed to compensate the charge excess of PSS − when PEDOT is dedoped and therefore the speed of electrochemical doping depends on the rate of the ionic flux across the electrolyte. [21] A comprehensive understanding of electrochemical and physical phenomena originating the response of electrolyte-gated transistors is crucial for improved handling and design of these devices. However, the lack of suitable tools for direct investigation of microscale effects has hindered the possibility to bridge the gap between experiments and theoretical models. In this contribution, a scanning probe setup is used to explore the operation mechanisms of organic electrochemical transistors b...

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“…Indeed, a new trend in the field of organson-chips and in vitro tissue models is to harness the potential offered by the integration of sensing units with the culture chambers to continuously monitor the system. [17][18][19] The present work falls in this area as we have developed a strategy for a sensing device for stem cell differentiation monitoring, with the potential to be integrated within a cell culture chamber. Our technology is based on the coupling of the electrochemical properties of poly (3,4ethylenedioxythiophene): polystyrene sulfonate (PEDOT:PSS), and the specificity brought by monoclonal antibodies targeting the analyte of choice.…”

Section: Introductionmentioning

confidence: 99%

“…[20] This property contributes to making PEDOT:PSS one of the materials of choice at the interface with biological systems. [18,21] Several devices have been developed based on this conducting polymer for a number of diverse applications embracing different fields such as tissue engineering, neural recording, neuromorphic computing, wearable and in vitro sensing. [22][23], [11], [24,25], [26][27][28] These materials hold promise for the electrical stimulation of osteogenic differentiation together with other electroactive materials and composite that have been explored for chronic electrical stimulation.…”

Section: Introductionmentioning

confidence: 99%

BMP-2 functionalized PEDOT:PSS-based OECTs for stem cell osteogenic differentiation monitoring

Decataldo

Druet

Pappa

et al. 2019

Flex. Print. Electron.

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Stem cell osteogenic differentiation is a complex process, associated with a number of events such as the secretion of collagen type I, osteopontin, osteonectin, osteocalcin and Bone Morphogenic Protein 2 (BMP-2). These molecules can be used as markers to monitor stem cell fate while studying the effects of a specific osteogenic differentiation treatment (e.g. electrical stimulation). Currently available techniques, such as the evaluation of the expression levels of specific genes and end-point biochemical assays, do not allow real-time monitoring of cellular processes, therefore overlooking potentially interesting information. This study explores a promising functionalization strategy towards on-line electrical monitoring of stem cell osteogenic differentiation process, using an organic electrochemical transistor (OECT) to detect cytokines of interest, secreted by cells during the osteogenic differentiation process, such as BMP-2. In this work, antibodies against BMP-2 were anchored on the poly(3,4-ethylenedioxythiophene):polystyrene (PEDOT:PSS) sulfonate gate electrode of an OECT. The biofunctionalization process was evaluated using multiple techniques such as Atomic Force Microscopy, Electrochemical Raman Spectroscopy, Quartz crystal microbalance. Electrode properties were assessed by running chronoamperometric studies, as well as by characterizing the PEDOT:PSS thin film resistance to ion flow by electrochemical impedance spectroscopy and OECT performance using transient (AC) measurements. Finally, a proof-of-concept, biosensor measurement was performed to test our functionalization strategy for sensing, proving that the antibody-functionalized OECTs were able to detect recombinant BMP-2 at levels that are comparable to those used for in vitro stimulation of bone regeneration via soluble osteoinductive factors.

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Transistor in a tube: A route to three-dimensional bioelectronics

Abstract: We report development of the first biomimetic transistor in a tube for continuous monitoring of 3D cell cultures.

Cited by 80 publications

References 47 publications

A highly sensitive molecular structural probe applied to in situ biosensing of metabolites using PEDOT:PSS

A highly sensitive molecular structural probe applied to in situ biosensing of metabolites using PEDOT:PSS

Microscopic Determination of Carrier Density and Mobility in Working Organic Electrochemical Transistors

BMP-2 functionalized PEDOT:PSS-based OECTs for stem cell osteogenic differentiation monitoring

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