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An Electrochemical CMOS biosensor array Using Phase-Only Modulation With 0.035%Phase Error and In-Pixel Averaging

IEEE TRANSACTIONS ON BIOMEDICAL CIRCUITS AND SYSTEMS 2025年第2期19卷 416-427页

作者： Jain, Aditi Chung, Saeromi Spencer, Eliah Aronoff Hall, Drew A. Univ Calif San Diego Dept Elect & Comp Engn La Jolla CA 92093 USA

This paper presents a 16 x 20 CMOS biosensor array based on electrochemical impedance spectroscopy (EIS), a highly sensitive label-free technique for rapid disease detection at the point-of-care. This high-density system implements polar-mode detection with phase-only EIS measurement over a 5 kHz - 1 MHz frequency range. The design features predominantly digital readout circuitry, ensuring scalability with technology, along with a load-compensated transimpedance amplifier, all within a 140 x 140 mu m(2) pixel. The architecture enables in-pixel digitization and accumulation, which increases the SNR by 10 dB for each 10x increase in readout time. Implemented in a 180 nm CMOS process, the 3 x 4 mm(2) chip achieves state-of-the-art performance with an rms phase error of 0.035% at 100 kHz through a duty-cycle insensitive phase detector and one of the smallest per pixel areas with in-pixel quantization.

关键词： Electrodes Impedance DNA biosensors Phase modulation Integrated circuit modeling Phased arrays Point-of-care (PoC) electrochemical impedance spectroscopy (EIS) biosensor array phase-to-digital converter

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Plasmon-Stimulated Colorimetry biosensor array for the Identification of Multiple Metabolites

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ACS APPLIED MATERIALS & INTERFACES 2024年第6期16卷 6849-6858页

作者： Tian, Lin Cao, Ming Cheng, Haorong Wang, Yanfei He, Changchun Shi, Xinxin Li, Tongxiang Li, Zhao Xuzhou Univ Technol Sch Mat & Chem Engn Xuzhou 221018 Peoples R China Xuzhou Univ Technol Sch Food Biol Engn Xuzhou 221018 Peoples R China

Rationally designing highly catalytic and stable nanozymes for metabolite monitoring is of great importance because of their huge potential in early disease diagnosis. Herein, a novel nanozyme based on hierarchically structured CuS/ZnS with a highly efficient peroxidase (POD)-mimic capability was developed and synthesized for multiple metabolite determination and recognition via the plasmon-stimulated biosensor array strategy. The designed nanozyme can simultaneously harvest plasmon triggered hot electron-hole pairs and generate photothermal properties, leading to a sharply boosted POD-mimic capability under 808 nm laser irradiation. Interestingly, because of the interaction diversity of the metabolite with POD-like nanomaterials, the unique inhibitory effect of metabolites on the POD-mimic activity could be the signal response as the differentiation. Thus, utilizing TMB as a typical chromogenic substrate in the addition of H2O2, the designed colorimetric biosensor array can produce diverse fingerprints for the three vital metabolisms (cysteine (Cys), ascorbic acid (AA), and glutathione (GSH)), which can be precisely identified by principal component analysis (PCA). Notably, a distinct fingerprint of a single metabolite with different levels and metabolite mixtures is also achieved with a detection limit of 1 mu M. Most importantly, cell lysis could be effectively discriminated by the biosensor assay, implying its great potential in clinical diagnosis.

关键词： plasmon CuS/ZnS photothermal effect nanozyme biosensor array specific identification

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Fading of nanocurcumin-based configured biosensor array for differentiation of carrier proteins in biological fluids

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MICROCHEMICAL JOURNAL 2022年 175卷 107169-107169页

作者： Rasouli, Zolaikha Ghavami, Raouf Univ Kurdistan Fac Sci Chem Dept Chemometr Lab POB 416 Sanandaj *** Iran

Herein, a simple, novel, and cost-effective biosensor array is developed for the differentiation of carrier proteins (i.e. human serum albumin (HSA), bovine serum albumin (BSA), transferrin (TRF), immunoglobulin G (IgG), fibrinogen (Fb) and casein (Cas) based on fading nanocurcumin in alkaline solutions. We found that the carrier proteins show different inhibitory effects with diverse extents on the alkaline decomposition of nanocurcumin. In the other words, in the presence of carrier proteins, the biosensor array produces fingerprint-like absorbance patterns to identify each carrier protein. The absorbance patterns of this biosensor array can be analyzed by linear discrimination analysis (LDA) and hierarchical cluster analysis (HCA). The six carrier proteins have been well discriminated in different concentrations levels. Furthermore, complex mixtures of HSA and TRF with a total concentration of 25 mu M and different mole ratios are also discriminated without errors. Also, the HSA as an example of carrier proteins has been well determined in the range of 5-75 mu M. The results revealed that the biosensor array shows high selectivity to the carrier proteins in the presence of other interfering substances. The analytical performance of the biosensor array is examined by the differentiation of carrier proteins in human urine and serum biofluids. It should be noted that the biosensor array is very simple, label-free, and selective, and only restricted sensor elements are required for attaining a high differentiation capability of carrier proteins.

关键词： biosensor array Nanocurcumin Carrier protein Differentiation Linear discrimination analysis Hierarchical clustering analysis

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Machine learning linked evolutionary biosensor array for highly sensitive and specific molecular identification

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biosensorS & BIOELECTRONICS 2020年 170卷 112670-112670页

作者： Kim, Haseong Seong, Wonjae Rha, Eugene Lee, Hyewon Kim, Seong Keun Kwon, Kil Koang Park, Kwang-Hyun Lee, Dae-Hee Lee, Seung-Goo Korea Res Inst Biosci & Biotechnol KRIBB Synthet Biol & Bioengn Res Ctr Daejeon 34141 South Korea KRIBB Dis Target Struct Res Ctr Daejeon 34141 South Korea Univ Sci & Technol KRIBB Sch Biotechnol Dept Biosyst & Bioengn Daejeon 34113 South Korea

Bacteria initiate complicated signaling cascades from the detection of intracellular metabolites or exogenous substances by hundreds of transcription factors, which have been widely investigated as genetically-encoded biosensors for molecular recognition. However, the limited number of transcription factors and their broad substrate specificity result in ambiguity in small molecule identification. This study presents a new small molecule fingerprinting technique using evolutionary biosensor arrays with a machine learning technique that can capture highly specific substrate signals. Employing multiple mutant transcription factors derived from a single transcription factor has effectively circumvented the limited availability of transcription factors induced by a small molecule of our interest. This method achieved up to 95.3% true positive rate for identifying small molecules, and the high-resolution protein engineering technique improved the limit of detection 75-fold. The signal trade-offs with background noises caused by the complex cellular biochemistry of mutant transcription factors enable the biosensor arrays to be more informative in terms of statistical variance. The machine learning technology, coupled with the single transcription factor-driven evolutionary biosensor array, will open new avenues for molecular fingerprinting technologies.

关键词： Genetically-encoded biosensors Machine learning Molecular identification Protein engineering biosensor array High-throughput screening system

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The placement position optimization of a biosensor array for wearable healthcare systems

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JOURNAL OF MECHANICAL SCIENCE AND TECHNOLOGY 2019年第7期33卷 3237-3244页

作者： Ha, Seulki Park, Sangheon Lim, Hyeoncheol Baek, Seung Ho Kim, Do Kyoung Yoon, Sang-Hee Inha Univ Dept Mech Engn Incheon South Korea LIG Nexl Co Ltd C4I Res Ctr Yongin Gyeonggi Do South Korea

Advancement in wearable healthcare technology allows a digital revolution in healthcare that is intended to extend life length and improve life quality. Until now, numerous efforts for wearable device-mediated healthcare systems have been focused on achieving accurate monitoring and robust operation by developing cutting-edge biosensors rather than by optimizing the placement position of well-established biosensors. Much therefore still remains unclear about the optimal position involved in biosensor placement. This leads to the need for systematic optimization of biosensor placement position. Here, the placement positions of 2 biosensor arrays (i.e., ECG-TC array and PPG-TC array) are optimized to achieve high-accuracy measurement and high-robustness operation in monitoring both body temperature and heart rate, which are commonly measured as core vital signs in wearable healthcare systems. The ECG-TC array is composed of an electrocardiography (ECG) sensor (for heart rate measurement) and a thermocouple (TC) sensor (for body temperature measurement) while the PPG-TC array consists of a photoplethysmography (PPG) sensor and a TC sensor. 34 major parts in the human body are scored in terms of monitoring accuracy (MA) and operational robustness (OR), which results in the MA index and OR index. Next, the body part having the maximum value, calculated as the product of two indices, is determined as the optimal placement position. The MA index is calculated from the signal magnitude of each biosensor and the OR index is assessed by quantifying the user accessibility, skin extensibility, and perspiration weight of each body part. Our study shows that the ECG-TC array needs to be placed on armpit, chest, and back thigh and the PPG-TC array on thumb, finger, and ear. This means the optimal placement position of biosensor-based wearable healthcare systems is affected by a combination of different biosensors. The findings of this study are expected to contribute to better und

关键词： Placement position Optimization biosensor array Wearable healthcare system Human body Material property

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A highly selective amperometric biosensor array for the simultaneous determination of glutamate, glucose, choline, acetylcholine, lactate and pyruvate

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BIOELECTROCHEMISTRY 2019年 128卷 100-108页

作者： Kucherenko, D. Yu. Kucherenko, I. S. Soldatkin, O. O. Topolnikova, Ya. V. Dzyadevych, S. V. Soldatkin, A. P. NAS Ukraine Lab Biomol Elect Inst Mol Biol & Genet 150 Zabolotnogo Str UA-03148 Kiev Ukraine Taras Shevchenko Natl Univ Kyiv Inst High Technol 64 Volodymyrska Str UA-01003 Kiev Ukraine Iowa State Univ Dept Mech Engn Ames IA 50011 USA

The work was aimed at the development of a biosensor array for the simultaneous determination of six solutes (glutamate, glucose, choline, acetylcholine, lactate, and pyruvate) in aqueous solutions. Enzymes selective for these substrates were immobilized on the surface of amperometric platinum disc electrodes and served as bioselective elements of a biosensor array. Direct enzymatic analysis by the developed biosensors provided high sensitivity to the tested substrates (limits of detection were 1-5 AM). The linear ranges of the biosensors were from 0.001-0.01 mM to 0.2-2.5 mM. The influence of solution pH, ionic strength and buffer capacity on the biosensor responses was investigated;the conditions for simultaneous operation of all the bioselective elements were optimized. The absence of any cross-influence of the substrates of enzymatic systems used was shown as well as a high selectivity of the biosensors and the absence of any impact of interfering substances (ascorbic acid, dopamine, cysteine, paracetamol). The developed biosensor array had good response reproducibility and storage stability. The array is suitable for rapid (0.5-1 min) and simple simultaneous determination of glutamate, glucose, choline, acetylcholine, lactate, and pyruvate in aqueous (biological) samples;furthermore, the creation of a single chip with six sensitive elements is possible as well as the addition of other biosensors. (C) 2019 Elsevier B.V. All rights reserved.

关键词： Amperometric biosensor biosensor array Neurotransmitter Glucose Glutamate Acetylcholine

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Electrogenerated chemiluminescence biosensor array for the detection of multiple AMI biomarkers

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SENSORS AND ACTUATORS B-CHEMICAL 2018年 257卷 60-67页

作者： Yang, Xiaolin Zhao, Ying Sun, Lijuan Qi, Honglan Gao, Qiang Zhang, Chengxiao Shaanxi Normal Univ Sch Chem & Chem Engn Key Lab Analyt Chem Life Sci Shaanxi Prov Xian 710119 Shaanxi Peoples R China

An electrogenerated chemiluminescence (ECL) biosensor array for the individual and simultaneous detection of multiple biomarkers has been developed at first time on the basis of the aptamer-based biosensor incorporating a versatile signal probe. As principle-of-proof, the acute myocardial infarction (AMI) biomarkers, myoglobin(Myo), cardiac troponin I(cTnI) and cardiac troponin T(cTnT) were chosen as model analytes. The biosensor array was fabricated by self-assembling thiolated specific ssDNA aptamers on the surface of gold electrodes, respectively. After each target analyte was bound to the capture probes and then to each corresponding biotinylated antibody, and finally to the versatile ECL signal probe, ECL signals were recorded using PMT or CCD as a detector. For PMT model, the developed method showed extremely low detection limits for 0.30 ng/mL cTnT, 31 pg/mL Myo, 0.79 pg/mL cTnI. For ECL image model, a biosensor array containing three target biosensors and a control biosensor was found to be highly sensitive, no cross-talking, and accurate towards simultaneous detection of the AMI biomarkers. This work demonstrates that the aptamer-based biosensor array with a versatile signal probe is a promising for ECL simultaneous detection of multi-biomarkers. (C) 2017 Elsevier B.V. All rights reserved.

关键词： biosensor array Electrogenerated chemiluminescence imaging Myoglobin Cardiac troponin I Cardiac troponin T

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A 16x20 Electrochemical CMOS biosensor array with In-Pixel Averaging Using Polar Modulation

A 16x20 Electrochemical CMOS Biosensor Array with In-Pixel A...

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IEEE Custom Integrated Circuits Conference (CICC)

作者： Hsu, Chung-Lun Sun, Alexander Zhao, Yunting Aronoff-Spencer, Eliah Hall, Drew A. Univ Calif San Diego Dept Elect & Comp Engn La Jolla CA 92093 USA Univ Calif San Diego Sch Med La Jolla CA 92093 USA

ISBN: (纸本)9781538624838

biosensors based on electrochemical impedance spectroscopy (EIS), an ultra-sensitive, label-free sensing technique, are a promising technology for precise and rapid disease diagnosis at the point-of-care (POC). However, EIS usually requires mixers and lock-in detection to measure both the magnitude and phase of the complex impedance. To address this issue, we report a 16x20 electrochemical biosensor array with on chip sensors that implements a polar-mode measurement method that allows the readout circuitry to be mostly digital and small enough to fit within a 140x140 mu m(2) pixel. The architecture enables in-pixel digitization and accumulation, which increases the SNR by 10 dB for each 10x increase in readout time. Implemented in a 0.18 mu m process, the 3x4 mm(2) chip achieves state-of-the-art performance with an rms phase error of 0.04% at 50 kHz and was used to measure hybridization of Zika virus oligonucleotides.

关键词： point-of-care (POC) electrochemical impedance spectroscopy (EIS) biosensor array phase-to-digital converter

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A Double-Side CMOS-CNT biosensor array With Padless Structure for Simple Bare-Die Measurements in a Medical Environment

A Double-Side CMOS-CNT Biosensor Array With Padless Structur...

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62nd IEEE International Solid-State Circuits Conference (ISSCC)

作者： Ahn, Jinhong Hong, Sang Hoon Park, Youngjune Seoul Natl Univ Seoul 151742 South Korea Kyung Hee Univ Dept Elect & Radio Engn Yongin 130701 South Korea Seoul Natl Univ Dept Elect Engn Seoul 151742 South Korea

ISBN: (纸本)9781479962242

This paper presents a double-side CMOS-carbon nanotube (CNT) sensor array for simple bare-die measurements in a medical environment based on a 0.35 mu m standard CMOS process. This scheme allows robust measurements due to its inherent back-side rectifying diodes with a high latch-up resistance. In particular, instead of using pads, only two contact metal structures: a wide ring structure around the sensor area on the front side and a plate structure at the backside are used for both power and single I/O line. The back-side rectification is made possible by creating VDD and VSS through the back-side and front-side, respectively. The single I/O line is conditioned such that it doubles as either the power source or the ground, depending on whether the chip is face down or face up. A modified universal asynchronous receiver/transmitter (UART) serial communication scheme with pulse based I/O signal transmission is developed to reduce the power degradation during the signaling intervals. In addition, communication errors and I/O power dissipation for the receiver path are minimized by using level sensitive switch control and double sampling difference amplifier. In order to implement these special functions, a controller chip with a special I/O protocol is designed. Using this controller chip, issuing commands and receiving data can both be performed on a single line and the results are flexibly measured through either the backside or the front side of the chip contacts. As a result, a stable operation of under 150 mW maximum power at 2 MHz data rate can be achieved. The double-side chips with 32 x 32 and 64 x 64 sensor arrays occupy areas of 1.9 x 2.3 mm(2) and 3.7 x 3.9 mm(2), respectively.

关键词： Backside rectification bare-die measurement biosensor array CMOS carbon nanotube (CNT) controller double-side flippable chip position level sensitive switch control medical pulse communication universal asynchronous receiver/transmitter (UART)

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High-Sensitivity InGaZnO FET Sensor array With Offset Self-Calibration for Multibiomarker Sensing

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IEEE TRANSACTIONS ON ELECTRON DEVICES 2025年第5期72卷 2740-2746页

作者： Li, Yao Zhou, Yuying Chen, Bing Zhang, Shuaidi Hu, Ke Li, Peiyun Lu, Congyan Wang, Jiawei Yang, Xiaonan Zhang, Feng Zhang, Wenchang Li, Ling Chinese Acad Sci Inst Microelect State Key Lab Fabricat Technol Integrated Circuits Beijing 100029 Peoples R China Univ Chinese Acad Sci Sch Integrated Circuits Beijing 100049 Peoples R China Zhengzhou Univ Affiliated Hosp 1 Dept Gastroenterol Zhengzhou 450052 Peoples R China Zhengzhou Univ Sch Informat Engn Zhengzhou 450001 Peoples R China

This work proposes a dual-gate InGaZnO thin-film transistor sensor array for label-free and cross-scale multiple biomarkers detection, including single-stranded deoxyribonucleic acid (ssDNA) and protein CA125. We exploit dual gate modulation for threshold voltage and CMOS-based SAR-assisted digital-to-analog converter (DAC) V-BG calibration circuit to eliminate initial V-TH offset variation caused by different functionalizations, which improve the reliability of the multibiomarker sensor array. At the same time, receptor enhancement on the indium gallium zinc oxide (IGZO) sensing membrane was detected by fluorescence assay, realizing higher sensitivity for biosensor. We demonstrate the sensor array response for pH in static and real-time mode, realizing near-Nernst limit sensitivity (55.02 mV/pH). Furthermore, at the top-gate configuration, with low operation voltage (0.1 V) and low offset variation (about 2 nA), the IGZO sensor array exhibits great performance for biomarker sensing which achieves sensitivity up to 4.426%/decade for ssDNA and 1102 nA/decade for CA125, with the limit of detection (LoD) of 1.67 aM for ssDNA and 0.1 fg/mL for CA125. This biosensor array provides a potential approach to realize miniaturization and high-density integration of multidimensional-biomarker detection.

关键词： Sensors Biomarkers Threshold voltage Sensor arrays Logic gates Proteins Electrodes DNA biosensors Sensitivity biosensor array indium gallium zinc oxide (IGZO) multiple-biomarker sensing offset calibration pH sensor thin-film transistors

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