translating-extracellular-electron-transfer-activities-with-organic

Translating Extracellular Electron Transfer Activities with Organic Electrochemical Transistors

Extracellular electron transfer (EET) is a process through which certain microorganisms can transfer electrons across their cell membranes to external ...

Northwestern University

Associative learning, a critical learning principle to improve an individual's adaptability, has been emulated by few organic electrochemical devices. However, complicated bias schemes, high write voltages, as well as process irreversibility hinder the further development of associative learning circuits. Here, by adopting a poly(3,4-ethylenedioxythiophene):tosylate/Polytetrahydrofuran composite as the active channel, we present a non-volatile organic electrochemical transistor that shows a write bias less than 0.8 V and retention time longer than 200 min without decoupling the write and read operations. By incorporating a pressure sensor and a photoresistor, a neuromorphic circuit is demonstrated with the ability to associate two physical inputs (light and pressure) instead of normally demonstrated electrical inputs in other associative learning circuits. To unravel the non-volatility of this material, ultraviolet-visible-near-infrared spectroscopy, X-ray photoelectron spectroscopy and grazing-incidence wide-angle X-ray scattering are used to characterize the oxidation level variation, compositional change, and the structural modulation of the poly(3,4-ethylenedioxythiophene):tosylate/Polytetrahydrofuran films in various conductance states. The implementation of the associative learning circuit as well as the understanding of the non-volatile material represent critical advances for organic electrochemical devices in neuromorphic applications.

Mimicking associative learning using an ion-trapping non-volatile synaptic organic electrochemical transistor.

The organic electrochemical transistor (OECT) represents a versatile and impactful electronic building block in the areas of printed electronics, bioelectronics, and neuromorphic computing. Significant efforts in OECTs have focused on device physics, new active material design and synthesis, and on preliminary implementation of individual transistors as proof-of-concept components for sensing and computation. However, as most of the current studies are based on single devices, the integration of OECTs into circuits or high-level systems has lagged. In this review, we focus on recent efforts to incorporate individual OECTs into digital, analog, and neuromorphic circuits, and lay out important considerations relevant for (hybrid) systems integration. We summarize the operation principles and the functions of OECT-based circuits and discuss the approaches for wireless power and data transmission for practicality in biological and bio-inspired applications. Finally, we comment on the future directions and challenges facing OECT circuits from both a fundamental and applied perspective.

Organic electrochemical transistors in bioelectronic circuits.

Three lactone-based rigid semiconducting polymers were designed to overcome major limitations in the development of n-type organic thermoelectrics, namely electrical conductivity and air stability. Experimental and theoretical investigations demonstrated that increasing the lactone group density by increasing the benzene content from 0 % benzene (P-0), to 50 % (P-50), and 75 % (P-75) resulted in progressively larger electron affinities (up to 4.37 eV), suggesting a more favorable doping process, when employing (N-DMBI) as the dopant. Larger polaron delocalization was also evident, due to the more planarized conformation, which is proposed to lead to a lower hopping energy barrier. As a consequence, the electrical conductivity increased by three orders of magnitude, to achieve values of up to 12 S cm and Power factors of 13.2 μWm  K were thereby enabled. These findings present new insights into material design guidelines for the future development of air stable n-type organic thermoelectrics.

Lactone Backbone Density in Rigid Electron-Deficient Semiconducting Polymers Enabling High n-type Organic Thermoelectric Performance.

A series of fully fused n-type mixed conduction lactam polymers , systematically increasing the alkyl side chain content, are synthesized via an inexpensive, nontoxic, precious-metal-free aldol polycondensation. Employing these polymers as channel materials in organic electrochemical transistors (OECTs) affords state-of-the-art n-type performance with  recording an OECT electron mobility of 1.20 × 10 cm V s and a μ* figure of merit of 1.83 F cm V s. In parallel to high OECT performance, upon solution doping with (4-(1,3-dimethyl-2,3-dihydro-1-benzoimidazol-2-yl)phenyl)dimethylamine (N-DMBI), the highest thermoelectric performance is observed for , with a maximum electrical conductivity of 7.67 S cm and a power factor of 10.4 μW m K. These results are among the highest reported for n-type polymers. Importantly, while this series of fused polylactam organic mixed ionic-electronic conductors (OMIECs) highlights that synthetic molecular design strategies to bolster OECT performance can be translated to also achieve high organic thermoelectric (OTE) performance, a nuanced synthetic approach must be used to optimize performance. Herein, we outline the performance metrics and provide new insights into the molecular design guidelines for the next generation of high-performance n-type materials for mixed conduction applications, presenting for the first time the results of a single polymer series within both OECT and OTE applications.

Synthetic Nuances to Maximize n-Type Organic Electrochemical Transistor and Thermoelectric Performance in Fused Lactam Polymers.

Organic electrochemical transistors (OECTs) and OECT-based circuitry offer great potential in bioelectronics, wearable electronics and artificial neuromorphic electronics because of their exceptionally low driving voltages (<1 V), low power consumption (<1 µW), high transconductances (>10 mS) and biocompatibility. However, the successful realization of critical complementary logic OECTs is currently limited by temporal and/or operational instability, slow redox processes and/or switching, incompatibility with high-density monolithic integration and inferior n-type OECT performance. Here we demonstrate p- and n-type vertical OECTs with balanced and ultra-high performance by blending redox-active semiconducting polymers with a redox-inactive photocurable and/or photopatternable polymer to form an ion-permeable semiconducting channel, implemented in a simple, scalable vertical architecture that has a dense, impermeable top contact. Footprint current densities exceeding 1 kA cm at less than ±0.7 V, transconductances of 0.2-0.4 S, short transient times of less than 1 ms and ultra-stable switching (>50,000 cycles) are achieved in, to our knowledge, the first vertically stacked complementary vertical OECT logic circuits. This architecture opens many possibilities for fundamental studies of organic semiconductor redox chemistry and physics in nanoscopically confined spaces, without macroscopic electrolyte contact, as well as wearable and implantable device applications.

Vertical organic electrochemical transistors for complementary circuits.

Electrochemical aptamer-based sensors are typically deployed as individual, passive, surface-functionalized electrodes, but they exhibit limited sensitivity especially when the area of the electrode is reduced for miniaturization purposes. We demonstrate that organic electrochemical transistors (electrolyte gated transistors with volumetric gating) can serve as on-site amplifiers to improve the sensitivity of electrochemical aptamer-based sensors. By monolithically integrating an Au working/sensing electrode, on-chip Ag/AgCl reference electrode, and Poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) counter electrode - also serving as the channel of an organic electrochemical transistor- we can simultaneously perform testing of organic electrochemical transistors and traditional electroanalytical measurement on electrochemical aptamer-based sensors including cyclic voltammetry and square-wave voltammetry. This device can directly amplify the current from the electrochemical aptamer-based sensor via the in-plane current modulation in the counter electrode/transistor channel. The integrated sensor can sense transforming growth factor beta 1 with 3 to 4 orders of magnitude enhancement in sensitivity compared to that in an electrochemical aptamer-based sensor (292 μA/dec vs. 85 nA/dec). This approach is believed to be universal, and can be applied to a wide range of tethered electrochemical reporter-based sensors to enhance sensitivity, aiding in sensor miniaturization and easing the burden on backend signal processing.

Organic electrochemical transistors as on-site signal amplifiers for electrochemical aptamer-based sensing.

Organic electrochemical transistors (OECTs) are ideal devices for translating biological signals into electrical readouts and have applications in bioelectronics, biosensing, and neuromorphic computing. Despite their potential, developing programmable and modular methods for living systems to interface with OECTs has proven challenging. Here we describe hybrid OECTs containing the model electroactive bacterium  that enable the transduction of biological computations to electrical responses. Specifically, we fabricated planar p-type OECTs and demonstrated that channel de-doping is driven by extracellular electron transfer (EET) from . Leveraging this mechanistic understanding and our ability to control EET flux via transcriptional regulation, we used plasmid-based Boolean logic gates to translate biological computation into current changes within the OECT. Finally, we demonstrated EET-driven changes to OECT synaptic plasticity. This work enables fundamental EET studies and OECT-based biosensing and biocomputing systems with genetically controllable and modular design elements.

A Hybrid Transistor with Transcriptionally Controlled Computation and Plasticity.

Implantable cell therapies and tissue transplants require sufficient oxygen supply to function and are limited by a delay or lack of vascularization from the transplant host. Previous exogenous oxygenation strategies have been bulky and had limited oxygen production or regulation. Here, we show an electrocatalytic approach that enables bioelectronic control of oxygen generation in complex cellular environments to sustain engineered cell viability and therapy under hypoxic stress and at high cell densities. We find that nanostructured sputtered iridium oxide serves as an ideal catalyst for oxygen evolution reaction at neutral pH. We demonstrate that this approach exhibits a lower oxygenation onset and selective oxygen production without evolution of toxic byproducts. We show that this electrocatalytic on site oxygenator can sustain high cell loadings (>60k cells/mm) in hypoxic conditions in vitro and in vivo. Our results showcase that exogenous oxygen production devices can be readily integrated into bioelectronic platforms, enabling high cell loadings in smaller devices with broad applicability.

Electrocatalytic on-site oxygenation for transplanted cell-based-therapies.

Bioresorbable electronic devices as temporary biomedical implants represent an emerging class of technology relevant to a range of patient conditions currently addressed with technologies that require surgical explantation after a desired period of use. Obtaining reliable performance and favorable degradation behavior demands materials that can serve as biofluid barriers in encapsulating structures that avoid premature degradation of active electronic components. Here, this work presents a materials design that addresses this need, with properties in water impermeability, mechanical flexibility, and processability that are superior to alternatives. The approach uses multilayer assemblies of alternating films of polyanhydride and silicon oxynitride formed by spin-coating and plasma-enhanced chemical vapor deposition , respectively. Experimental and theoretical studies investigate the effects of material composition and multilayer structure on water barrier performance, water distribution, and degradation behavior. Demonstrations with inductor-capacitor circuits, wireless power transfer systems, and wireless optoelectronic devices illustrate the performance of this materials system as a bioresorbable encapsulating structure.

Bioresorbable Multilayer Organic-Inorganic Films for Bioelectronic Systems.

Organic electrochemical transistors (OECTs) are ideal devices for translating biological signals into electrical readouts and have applications in bioelectronics, biosensing, and neuromorphic computing. Despite their potential, developing programmable and modular methods for living systems to interface with OECTs has proven challenging. Here we describe hybrid OECTs containing the model electroactive bacterium Shewanella oneidensis that enable the transduction of biological computations to electrical responses. Specifically, we fabricated planar p-type OECTs and demonstrated that channel de-doping is driven by extracellular electron transfer (EET) from S. oneidensis. Leveraging this mechanistic understanding and our ability to control EET flux via transcriptional regulation, we used plasmid-based Boolean logic gates to translate biological computation into current changes within the OECT. Finally, we demonstrated EET-driven changes to OECT synaptic plasticity. This work enables fundamental EET studies and OECT-based biosensing and biocomputing systems with genetically controllable and modular design elements.

A hybrid transistor with transcriptionally controlled computation and plasticity.

Ion transport in organic mixed ionic-electronic conductors (OMIECs) is crucial due to its direct impact on device response time and operating mechanisms but is often assessed indirectly or necessitates extra assumptions. Operando x-ray fluorescence (XRF) is a powerful, direct probe for elemental characterization of bulk OMIECs and was used to directly quantify ion composition and mobility in a model OMIEC, poly(3,4-ethylenedioxythiophene)-poly(styrene sulfonate) (PEDOT:PSS), during device operation. The first cycle revealed slow electrowetting and cation-proton exchange. Subsequent cycles showed rapid response with minor cation fluctuation (~5%). Comparison with optical-tracked electrochromic fronts revealed mesoscale structure-dependent proton transport. The calculated effective ion mobility demonstrated thickness-dependent behavior, emphasizing an interfacial ion transport pathway with a higher mobile ion density. The decoupling of interfacial effects on bulk ion mobility and the decoupling of cation and proton migration elucidate ion transport in conventional and emerging OMIEC-based devices and has broader implications for other ionic conductors writ large.

Direct quantification of ion composition and mobility in organic mixed ionic-electronic conductors.

Increasing demand for bio-interfaced human-machine interfaces propels the development of organic neuromorphic electronics with small form factors leveraging both ionic and electronic processes. Ion-based organic electrochemical transistors (OECTs) showing anti-ambipolarity (OFF-ON-OFF states) reduce the complexity and size of bio-realistic Hodgkin-Huxley(HH) spiking circuits and logic circuits. However, limited stable anti-ambipolar organic materials prevent the design of integrated, tunable, and multifunctional neuromorphic and logic-based systems. In this work, a general approach for tuning anti-ambipolar characteristics is presented through assembly of a p-n bilayer in a vertical OECT (vOECT) architecture. The vertical OECT design reduces device footprint, while the bilayer material tuning controls the anti-ambipolarity characteristics, allowing control of the device's on and off threshold voltages, and peak position, while reducing size thereby enabling tunable threshold spiking neurons and logic gates. Combining these components, a mimic of the retinal pathway reproducing the wavelength and light intensity encoding of horizontal cells to spiking retinal ganglion cells is demonstrated. This work enables further incorporation of conformable and adaptive OECT electronics into biointegrated devices featuring sensory coding through parallel processing for diverse artificial intelligence and computing applications.

Tunable anti-ambipolar vertical bilayer organic electrochemical transistor enable neuromorphic retinal pathway.

Developing nerve grafts with intact mesostructures, superior conductivity, minimal immunogenicity, and improved tissue integration is essential for the treatment and restoration of neurological dysfunctions. A key factor is promoting directed axon growth into the grafts. To achieve this, biohybrid nerves are developed using decellularized rat sciatic nerve modified by in situ polymerization of poly(3,4-ethylenedioxythiophene) (PEDOT). Nine biohybrid nerves are compared with varying polymerization conditions and cycles, selecting the best candidate through material characterization. These results show that a 1:1 ratio of FeCl oxidant to ethylenedioxythiophene (EDOT) monomer, cycled twice, provides superior conductivity (>0.2 mS cm), mechanical alignment, intact mesostructures, and high compatibility with cells and blood. To test the biohybrid nerve's effectiveness in promoting motor axon growth, human Spinal Cord Spheroids (hSCSs) derived from HUES 3 Hb9:GFP cells are used, with motor axons labeled with green fluorescent protein (GFP). Seeding hSCS onto one end of the conduit allows motor axon outgrowth into the biohybrid nerve. The construct effectively promotes directed motor axon growth, which improves significantly after seeding the grafts with Schwann cells. This study presents a promising approach for reconstructing axonal tracts in humans.

Decellularized Biohybrid Nerve Promotes Motor Axon Projections.

The fundamental challenge in electron-transporting organic mixed ionic-electronic conductors (OMIECs) is simultaneous optimization of electron and ion transport. Beginning from Y6-type/U-shaped non-fullerene solar cell acceptors, we systematically synthesize and characterize molecular structures that address the aforementioned challenge, progressively introducing increasing numbers of oligoethyleneglycol (OEG; g) sidechains from 1 g to 3 g, affording OMIECs 1gY, 2gY, and 3gY, respectively. The crystal structure of 1gY preserves key structural features of the Yn series: a U-shaped/planar core, close π-π molecular stacking, and interlocked acceptor groups. Versus inactive Y6 and Y11, all of the new glycolated compounds exhibit mixed ion-electron transport in both conventional organic electrochemical transistor (cOECT) and vertical OECT (vOECT) architectures. Notably, 3gY with the highest OEG density achieves a high transconductance of 16.5 mS, an on/off current ratio of ~10, and a turn-on/off response time of 94.7/5.7 ms in vOECTs. Systematic optoelectronic, electrochemical, architectural, and crystallographic analysis explains the superior 3gY-based OECT performance in terms of denser ngY OEG content, increased crystallite dimensions with decreased long-range crystalline order, and enhanced film hydrophilicity which facilitates ion transport and efficient redox processes. Finally, we demonstrate an efficient small-molecule-based complementary inverter using 3gY vOECTs, showcasing the bioelectronic applicability of these new small-molecule OMIECs.

Article	Year
Mimicking associative learning using an ion-trapping non-volatile synaptic organic electrochemical transistor. Nature communications\| PubMed ID: 33931638	2021
Organic electrochemical transistors in bioelectronic circuits. Biosensors & bioelectronics\| PubMed ID: 34197997	2021
Lactone Backbone Density in Rigid Electron-Deficient Semiconducting Polymers Enabling High n-type Organic Thermoelectric Performance. Angewandte Chemie (International ed. in English)\| PubMed ID: 34797584	2022
Synthetic Nuances to Maximize n-Type Organic Electrochemical Transistor and Thermoelectric Performance in Fused Lactam Polymers. Journal of the American Chemical Society\| PubMed ID: 35257589	2022
Vertical organic electrochemical transistors for complementary circuits. Nature\| PubMed ID: 36653571	2023
Organic electrochemical transistors as on-site signal amplifiers for electrochemical aptamer-based sensing. Nature communications\| PubMed ID: 36966131	2023
A Hybrid Transistor with Transcriptionally Controlled Computation and Plasticity. bioRxiv : the preprint server for biology\| PubMed ID: 37645977	2023
Electrocatalytic on-site oxygenation for transplanted cell-based-therapies. Nature communications\| PubMed ID: 37945597	2023
Bioresorbable Multilayer Organic-Inorganic Films for Bioelectronic Systems. Advanced materials (Deerfield Beach, Fla.)\| PubMed ID: 38339983	2024
A hybrid transistor with transcriptionally controlled computation and plasticity. Nature communications\| PubMed ID: 38383505	2024
Direct quantification of ion composition and mobility in organic mixed ionic-electronic conductors. Science advances\| PubMed ID: 38657078	2024
Tunable anti-ambipolar vertical bilayer organic electrochemical transistor enable neuromorphic retinal pathway. Nature communications\| PubMed ID: 39060249	2024
Decellularized Biohybrid Nerve Promotes Motor Axon Projections. Advanced healthcare materials\| PubMed ID: 39219219	2024
Small-Molecule Mixed Ionic-Electronic Conductors for Efficient N-Type Electrochemical Transistors: Structure-Function Correlations. Angewandte Chemie (International ed. in English)\| PubMed ID: 39312509	2025

Xudong Ji

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