Immunoassay Multiplexing on a Complementary Metal Oxide Semiconductor Photodiode Array.

Bence Nagy,Mohammed A Al-Rawhani,Boon Chong Cheah,Michael P Barrett,David R S Cumming

doi:10.1021/acssensors.7b00972

Bence Nagy, Mohammed A Al-Rawhani + Show 3 more

Open Access

https://doi.org/10.1021/acssensors.7b00972

Copy DOI

Journal: ACS sensors	Publication Date: Apr 13, 2018
Citations: 10	License type: cc-by

Affiliation: University of Glasgow

Abstract

Scalable immunoassay multiplexing offers a route to creating rapid point-of-care (POC) diagnostics. We present a method for multiplexing immunoassays on the surface of a complementary metal oxide semiconductor (CMOS) sensor array integrated circuit (IC) without the use of physical separators such as wells or channels. Major advantages of using a CMOS sensor array include low mass-manufacturing costs, the possibility to multiplex multiple assays on a single IC, and improved signal when averaging multiple sensors, along with providing a platform where wash steps can be incorporated to maximize selectivity and sensitivity compared to paper based lateral flow immunoassay. The device was able to differentiate between samples containing either, neither, or both rabbit anti-mouse (RAM) antibodies and/or anti-HIV gp120 antibodies in serum using a gold-nanoparticle promoted silver enhancement immunoassay. HIV antibody concentrations down to 100 μg/mL were readily detected, which is three times lower than those typically found in infected humans (300–500 μg/mL), and the limit of detection was 10 μg/mL.

Highlights

M any medical tests are invasive, time-consuming, and usually require specialist medical centers
While Complementary metal oxide semiconductor (CMOS) possesses many of the required attributes of a biosensor technology, a certain amount of post-processing is necessary, and we show how a readily available epoxy based photoresist used for microelectro-mechanical systems, SU-8, can be exploited to facilitate assay immobilization technology, making multiple assays on a single chip possible
The system we present is analogous to an ELISA type assay but miniaturized and amenable to simple electronic readout using a smartphone

Summary

Introduction

M any medical tests are invasive, time-consuming, and usually require specialist medical centers. The work presented here provides a step in that direction through detection of anti-HIV and rabbit anti-mouse (RAM) antibodies on a hand-held chip-based device (Figure 1). Antibodies are soluble proteins that circulate in blood and bind to foreign molecules (antigens) as part of the adaptive immune response.[11] Antibodies are frequently exploited in immunoassays for diagnostic purposes as their production is in direct response to the presence of foreign antigens in the host system. We demonstrate concurrent, interference-free execution of two optical immunoassays on the surface of a CMOS sensor array chip to detect antibodies targeted to the immunodominant gp[120] antigen of HIV, and antibodies to a second antigen (mouse IgG), demonstrating the potential to develop a multiplexed assay system on the surface of a CMOS sensor array. In the RAM assay, rabbit antimouse antibodies bind to printed mouse antibodies on the surface of the chip.

Methods

Results

Conclusion