A CMOS Multi-Modal Electrochemical and Impedance Cellular Sensing Array for Massively Paralleled Exoelectrogen Screening

Kumashi, Sagar; Jung, Doohwan; Park, Jong Seok; Tejedor-Sanz, Sara; Grijalva, Sandra I.; Wang, Adam; Li, Sensen; Cho, Hee Cheol; Ajo‐Franklin, Caroline M.; Wang, Hua

doi:10.1109/tbcas.2021.3068710

Cited by 27 publications

(16 citation statements)

References 42 publications

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“…Numerous biological and biomedical applications, such as cell-based assays/actuators, , implantable devices, , wearable electronics, drug/chemical biomonitoring, and synthetic biology rely primarily on electrode–cell or electrode–tissue interfaces with good biocompatibility, low impedance, high signal-to-noise ratio (SNR), long-term electrochemical stability, and minimum biofouling. These applications have broad and profound impacts including broadening fundamental understanding of biological processes through organ-on-chip devices, − treating brain injuries via neuroprosthesis, − and accelerating drug discovery with multi-modal cell-based sensors. − The electrode–cell/–tissue interfaces enable spatiotemporal recording of various cellular signals, for example, intra-/extra-cellular potentials, local field potentials (LFPs), cell–cell/cell–surface impedances, as well as bioelectrical stimulation and a wide variety of electrochemical reactions. ,,,,− For intimate monitoring of cellular parameters, there is a considerably growing interest in improving spatiotemporal resolution, increasing the total field-of-view (FoV), minimizing the device invasiveness, and boosting the number of simultaneous parallel readout channels. , Consequently, enhancing spatial resolution entails aggressively trimming the electrode sizes toward subcellular features (<5 μm) and scaling the total FoV to the tissue-level monitoring (>2–3 mm), a feat that requires extremely dense yet large-scale microelectrode arrays (MEAs) on rigid or flexible substrates with high reliability. However, such extreme miniaturization of electrodes inevitably limits the electrodes’ electrochemically active area and drastically increases the electrode–electrolyte or electrode–cell interfacial impedance. , The increased interfacial impedance directly raises thermal noise that deteriorates interface SNR and consequently constrains any electrical or electrochemical detection. , Furthermore, many in vivo (e.g., pacemakers and neuroprosthetics) and in vitro (e.g., lab-on-chip devices with cell-based assays) applications demand low electrode–cell interfacial impedance to support cellular bioelectrical stimulation with minimal invasiveness.…”

Section: Introductionmentioning

confidence: 99%

“…Numerous biological and biomedical applications, such as cellbased assays/actuators, 1,2 implantable devices, 3,4 wearable electronics, 5 drug/chemical biomonitoring, 6 and synthetic biology 7 rely primarily on electrode−cell or electrode−tissue interfaces with good biocompatibility, low impedance, high signal-to-noise ratio (SNR), long-term electrochemical stability, and minimum biofouling. These applications have broad and profound impacts including broadening fundamental understanding of biological processes through organ-on-chip devices, 8−12 treating brain injuries via neuroprosthesis, 13−15 and accelerating drug discovery with multi-modal cell-based sensors.…”

Section: ■ Introductionmentioning

confidence: 99%

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Impedance Characterization and Modeling of Subcellular to Micro-sized Electrodes with Varying Materials and PEDOT:PSS Coating for Bioelectrical Interfaces

Wang

Jung

Lee

et al. 2021

ACS Appl. Electron. Mater.

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Electrode-to-cell/tissue interfaces with high biocompatibility, low impedance, and long-term chemical and mechanical stability are of paramount importance in numerous biological and biomedical applications. For meticulous monitoring of biological parameters, there is a rapidly growing interest in sensing at subcellular levels with radically improved spatiotemporal resolution, which necessitates ultra-miniaturized electrodes with significant reduction in electrode contact sizes. Such aggressive electrode downsizing inevitably impacts the electrochemical interfaces, with the consequences still poorly understood. This paper reports the first systematic analysis of the interfacial electrochemical impedance spectroscopy of electrodes comprising a variety of biocompatible electrode materials consisting of gold (Au), platinum (Pt), indium tin oxide, and titanium nitride (TiN) coated with/without an organic polymer, poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS), with electrode diameters (D) ranging from millimeter to subcellular (<10 μm) dimensions. PEDOT:PSS-coated electrodes have greater Faradaic charge-transfer capability and capacitive coupling compared to their uncoated counterparts. At D = 10–200 μm, the PEDOT:PSS coating reduces the electrode interfacial impedance at 1 kHz by up to ×101.6, while at D > 200 μm, the effect is lessened due to the dominance of solution, or bulk electrolyte, and routing resistance. The low interfacial impedance of PEDOT:PSS-coated electrodes makes them promising candidates for next-generation bioelectrical interfaces with subcellular spatial resolution.

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Section: Introductionmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

Impedance Characterization and Modeling of Subcellular to Micro-sized Electrodes with Varying Materials and PEDOT:PSS Coating for Bioelectrical Interfaces

Wang

Jung

Lee

et al. 2021

ACS Appl. Electron. Mater.

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“…In Kumashi et al (2021), a CMOS sensor array with 256 pixel channels is fabricated based on the 130-nm BiCMOS process, which is used for electrochemical reaction and impedance detection of the biological surface as shown in Figure 15. This sensor array has 16 parallel readout channels, so it can measure high-throughput data quickly and process different samples.…”

Section: Figure 12mentioning

confidence: 99%

A review and analysis of current-mode biosensing front-end ICs for nanopore-based DNA sequencing

et al. 2022

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Bio-sensors connect the biological world with electronic devices, widely used in biomedical applications. The combination of microelectronic and medical technologies makes biomedical diagnosis more rapid, accurate, and efficient. In this article, the current-mode biosensing front-end integrated circuits (ICs) for nanopore-based DNA sequencing are reviewed and analyzed, aiming to present their operation theories, advantages, limitations, and performances including gain, bandwidth, noise, and power consumption. Because biological information and external interference are contained in extremely weak sensing current, usually at the pA or nA level, it is challenging to accurately detect and restore the desired signals. Based on the requirements of DNA sequencing, this paper shows three circuit topologies of biosensing front-end, namely, discrete-time, continuous-time, and current-to-frequency conversion types. This paper also makes an introduction to the current-mode sensor array for DNA sequencing. To better review and evaluate the research of the state-of-the-art, the most relevant published works are summarized and compared. The review and analysis would help the researchers be familiar with the requirements, constraints, and methods for current-mode biosensing front-end IC designs for nanopore-based DNA sequencing.

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“…Thus, it enables potentiostatic control in each well compared to purely passive voltage sensing in 2-electrode arrangements (Szydlowski et al, 2022). Noteworthy, this is also clearly different and advantageous when being compared to previous work (Kumashi et al, 2021;Molderez et al, 2021) that offers a high degree of parallelization in terms of working electrodes, but makes use of a shared reaction chamber. Thus, the ec-MP introduced here also allows the study of simultaneously and truly independently electroactive pure and mixed cultures over time, for example, in different media or at different pH.…”

Section: Introductionmentioning

confidence: 99%

Electrochemical Microwell Plate to Study Electroactive Microorganisms in Parallel and Real-Time

Kuchenbuch

Frank

Ramos

et al. 2022

Front. Bioeng. Biotechnol.

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Microbial resource mining of electroactive microorganism (EAM) is currently methodically hampered due to unavailable electrochemical screening tools. Here, we introduce an electrochemical microwell plate (ec-MP) composed of a 96 electrochemical deepwell plate and a recently developed 96-channel multipotentiostat. Using the ec-MP we investigated the electrochemical and metabolic properties of the EAM models Shewanella oneidensis and Geobacter sulfurreducens with acetate and lactate as electron donor combined with an individual genetic analysis of each well. Electrochemical cultivation of pure cultures achieved maximum current densities (jmax) and coulombic efficiencies (CE) that were well in line with literature data. The co-cultivation of S. oneidensis and G. sulfurreducens led to an increased current density of jmax of 88.57 ± 14.04 µA cm−2 (lactate) and jmax of 99.36 ± 19.12 µA cm−2 (lactate and acetate). Further, a decreased time period of reaching jmax and biphasic current production was revealed and the microbial electrochemical performance could be linked to the shift in the relative abundance.

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A CMOS Multi-Modal Electrochemical and Impedance Cellular Sensing Array for Massively Paralleled Exoelectrogen Screening

Cited by 27 publications

References 42 publications

Impedance Characterization and Modeling of Subcellular to Micro-sized Electrodes with Varying Materials and PEDOT:PSS Coating for Bioelectrical Interfaces

Impedance Characterization and Modeling of Subcellular to Micro-sized Electrodes with Varying Materials and PEDOT:PSS Coating for Bioelectrical Interfaces

A review and analysis of current-mode biosensing front-end ICs for nanopore-based DNA sequencing

Electrochemical Microwell Plate to Study Electroactive Microorganisms in Parallel and Real-Time

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