Silicon-based Integrated Microarray Biochips for Biosensing and Biodetection Applications

The silicon-based integrated microarray biochip (IMB) is an inter-disciplinary research direction of microelectronics and biological science. It has caught the attention of both industry and academia, in applications such as deoxyribonucleic acid (DNA) and immunological detection, medical inspection and point-of-care (PoC) diagnosis, as well as food safety and environmental surveillance. Future biodetection strategies demand biochips with high sensitivity, miniaturization, integration, parallel, multi-target and even intelligence capabilities. In this chapter, a comprehensive investigation of current research on state-of-the-art silicon-based integrated microarray biochips is presented. These include the electrochemical biochip, magnetic tunnelling junction (MTJ) based biochip, giant magnetoresistance (GMR) biochip and integrated oscillator-based biochip. The principles, methodologies and challenges of the aforementioned biochips will also be discussed and compared from all aspects, e.g., sensitivity, fabrication complexity and cost, compatibility with silicon-based complementary metal-oxide-semiconductor (CMOS) technology, multi-target detection capabilities, signal processing and system integrations, etc. In this way, we discuss future silicon-based fully integrated biochips, which could be used for portable medical detection and low cost PoC diagnosis applications

A handheld high-sensitivity micro-NMR CMOS platform with B-field stabilization for multi-type biological/chemical assays

We report a micro-nuclear magnetic resonance (NMR) system compatible with multi-type biological/chemical lab-on-a-chip assays. Unified in a handheld scale (dimension: 14 x 6 x 11 cm³, weight: 1.4 kg), the system is capable to detect<100 pM of Enterococcus faecalis derived DNA from a 2.5 μL sample. The key components are a portable magnet (0.46 T, 1.25 kg) for nucleus magnetization, a system PCB for I/O interface, an FPGA for system control, a current driver for trimming the magnetic (B) field, and a silicon chip fabricated in 0.18 μm CMOS. The latter, integrated with a current-mode vertical Hall sensor and a low-noise readout circuit, facilitates closed-loop B-field stabilization (2 mT → 0.15 mT), which otherwise fluctuates with temperature or sample displacement. Together with a dynamic-B-field transceiver with a planar coil for micro-NMR assay and thermal control, the system demonstrates: 1) selective biological target pinpointing; 2) protein state analysis; and 3) solvent-polymer dynamics, suitable for healthcare, food and colloidal applications, respectively. Compared to a commercial NMR-assay product (Bruker mq-20), this platform greatly reduces the sample consumption (120x), hardware volume (175x), and weight (96x)

Real-time DNA microarray analysis

We present a quantification method for affinity-based DNA microarrays which is based on the real-time measurements of hybridization kinetics. This method, i.e. real-time DNA microarrays, enhances the detection dynamic range of conventional systems by being impervious to probe saturation in the capturing spots, washing artifacts, microarray spot-to-spot variations, and other signal amplitude-affecting non-idealities. We demonstrate in both theory and practice that the time-constant of target capturing in microarrays, similar to all affinity-based biosensors, is inversely proportional to the concentration of the target analyte, which we subsequently use as the fundamental parameter to estimate the concentration of the analytes. Furthermore, to empirically validate the capabilities of this method in practical applications, we present a FRET-based assay which enables the real-time detection in gene expression DNA microarrays

Sensor Technology for Opening New Pathways in Diagnosis and Therapeutics of Breast, Lung, Colorectal and Prostate Cancer

This study analyzes the interaction between sensor research and technology and different types of cancer (breast, lung, colorectal, and prostate) with the goal of detecting new directions for improving diagnosis and therapeutics in medicine. This study develops an approach to computational scientometrics based on data from the Web of Science from the 1991 to 2021 period. The results of this analysis show the vital role of biosensors and electrochemical biosensors applied in breast cancer, lung cancer, and prostate cancer research. Instead, scientific research of optical sensors is developing main technological trajectories in breast, prostate, and colorectal cancer for improving diagnostics. Finally, oxygen sensor research has a main technological development in breast and lung cancer for new applications in breath analysis directed to treatment processes. Preliminary results presented here clearly illustrate the evolutionary paths of sensor research and technologies that have great potential for developing incremental and radical innovations in cancer diagnosis and therapies. These conclusions are, of course, tentative. There is a need for much more detailed research based on other aspects and factors for detecting stable technological trajectories that can foster the technology transfer of new sensor in cancer research for improving diagnosis and therapeutics, reducing, whenever possible, world-wide mortality of cancer in society.JEL Classification: I10, O30, O31, O32; O33. Doi: 10.28991/HIJ-2022-03-03-010 Full Text: PD

Low power cmos potentiometric circuit design for label-free DNA detection

DNA detector is one of the main way to use in order to detect diseases, preventing crime and so on. The DNA detecting process is limited due to the bulky and expensive existing DNA detector machine. As the demand of the small, portable and inexpensive biosensor for point-of-care testing aid and medical diagnostic, the research and development of biosensor are increasing exponentially every year. The aim of this work is to develop an on-chip Complementary Metal Oxide Semiconductor (CMOS) biosensor circuit based on the charge-modulated field effect transistor (CMFET) for a label-free deoxyribonucleic acid (DNA) detection. This project focusing on low voltage and low power design potentiometric DNA detection circuit. Overall of detection circuit consists of two main circuits which are self-cascode source drain follower and two-stage differential amplifier. The proposed detection circuit is designed and simulates using 0.13 µm Silterra CMOS fabrication with 1.2 V supply. The power consumption of the improved source-drain follower circuit is 1.36 µW and with gain of 0.998 dB. The two-stage differential amplifier achives a voltage gain of 56.02 dB and high common mode rejection ration (CMRR) of 90 dB

Highly sensitive and label-free digital detection of whole cell E. coli with interferometric reflectance imaging

Bacterial infectious diseases are a major threat to human health. Timely and sensitive pathogenic bacteria detection is crucial in identifying the bacterial contaminations and preventing the spread of infectious diseases. Due to limitations of conventional bacteria detection techniques there have been concerted research efforts towards development of new biosensors. Biosensors offering label free, whole bacteria detection are highly desirable over those relying on label based or pathogenic molecular components detection. The major advantage is eliminating the additional time and cost required for labeling or extracting the desired bacterial components. Here, we demonstrate rapid, sensitive and label free E. coli detection utilizing interferometric reflectance imaging enhancement allowing for visualizing individual pathogens captured on the surface. Enabled by our ability to count individual bacteria on a large sensor surface, we demonstrate a limit of detection of 2.2 CFU/ml from a buffer solution with no sample preparation. To the best of our knowledge, this high level of sensitivity for whole E. coli detection is unprecedented in label free biosensing. The specificity of our biosensor is validated by comparing the response to target bacteria E. coli and non target bacteria S. aureus, K. pneumonia and P. aeruginosa. The biosensor performance in tap water also proves that its detection capability is unaffected by the sample complexity. Furthermore, our sensor platform provides high optical magnification imaging and thus validation of recorded detection events as the target bacteria based on morphological characterization. Therefore, our sensitive and label free detection method offers new perspectives for direct bacterial detection in real matrices and clinical samples.First author draf

Targeted Deposition of Antibodies on a Multiplex CMOS Microarray and Optimization of a Sensitive Immunoassay Using Electrochemical Detection

The CombiMatrix ElectraSense microarray is a highly multiplex, complementary metal oxide semiconductor with 12,544 electrodes that are individually addressable. This platform is commercially available as a custom DNA microarray; and, in this configuration, it has also been used to tether antibodies (Abs) specifically on electrodes using complementary DNA sequences conjugated to the Abs.An empirical method is described for developing and optimizing immunoassays on the CombiMatrix ElectraSense microarray based upon targeted deposition of polypyrrole (Ppy) and capture Ab. This process was automated using instrumentation that can selectively apply a potential or current to individual electrodes and also measure current generated at the electrodes by an enzyme-enhanced electrochemical (ECD) reaction. By designating groups of electrodes on the array for different Ppy deposition conditions, we determined that the sensitivity and specificity of a sandwich immunoassay for staphylococcal enterotoxin B (SEB) is influenced by the application of different voltages or currents and the application time. The sandwich immunoassay used a capture Ab adsorbed to the Ppy and a reporter Ab labeled for fluorescence detection or ECD, and results from these methods of detection were different.Using Ppy deposition conditions for optimum results, the lower limit of detection for SEB using the ECD assay was between 0.003 and 0.01 pg/ml, which represents an order of magnitude improvement over a conventional enzyme-linked immunosorbant assay. In the absence of understanding the variables and complexities that affect assay performance, this highly multiplexed electrode array provided a rapid, high throughput, and empirical approach for developing a sensitive immunoassay

A Multichannel DNA SoC for Rapid Point-of-Care Gene Detection

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