학술논문

Light Absorption Measurement With a CMOS Biochip for Quantitative Immunoassay Based Point-of-Care Applications
Document Type
Periodical
Source
IEEE Transactions on Biomedical Circuits and Systems IEEE Trans. Biomed. Circuits Syst. Biomedical Circuits and Systems, IEEE Transactions on. 15(3):369-379 Jun, 2021
Subject
Bioengineering
Components, Circuits, Devices and Systems
Absorption
Biomedical measurement
Immune system
Optical variables measurement
Optical variables control
Optical sensors
Biomedical optical imaging
CMOS biochip
enzyme kinetics
immunoassay
in-vitro diagnostics (IVD)
photometer
point-of-care (PoC) diagnostics
prostate-specific antigen (PSA)
Language
ISSN
1932-4545
1940-9990
Abstract
We present a CMOS biochip-based photometer for quantitative immunoassay diagnostics. The photometer quantifies the concentration of antigens based on light absorption, which allows for a low-cost implementation without expensive optical components. We propose a light controller to lower the start-up and settling time of the light source to 30 seconds, to facilitate fast measurement starts, and to decrease the overall measurement times. The application-specific integrated circuit (ASIC) contains a 6 x 7-sensor array with 100 $\boldsymbol{\mu }$m x 100 $\boldsymbol{\mu }$m photodiodes that serve as signal transducers. The ASIC was developed in a normal 0.35-$\boldsymbol{\mu }$m CMOS technology, avoiding the need for expensive post-CMOS processes. We present our strategy for the assembly of the ASIC and the immobilization of antibodies. For its first time, we demonstrate the quantification of prostate specific antigen (PSA) with an optoelectronic CMOS biochip using this approach. A PSA immunoassay is performed on the top surface of the CMOS sensor array, enzyme kinetics and PSA concentration are measured within 6 minutes with a limit of detection (LoD) of 0.5 ng/ml, which meets clinical testing requirements. We achieve an overall coefficient of variation (CV) of 7%, which is good compared to other point-of-care (PoC) systems.