Complementary metal oxide semiconductor (CMOS) technology has made personal mobile computing and communications an everyday part of life. In this paper we present a nanophotonic integrated CMOS-based biosensor that will pave the way for future personalized medical diagnostics. To achieve our aim, we have monolithically integrated plasmonic nanostructures with a CMOS photodiode. Following this approach of monolithic nanophotonics–microelectronics integration, we have successfully developed a miniaturized nanophotonic sensor system with direct electrical readout, which eliminates the need of bulky and costly equipment that is presently used for interrogation of nanophotonic sensors. The optical sensitivity of the plasmonic nanostructures is measured to be 275 nm/refractive index unit (RIU), which translates to an electrical sensitivity of 5.8 V/RIU in our integrated sensor system. This advance is the first demonstration of monolithic integration of nanophotonic structures with CMOS detectors and is a crucial step toward translating laboratory based nanophotonic sensing systems to portable, low-cost, and digital formats.

Metabolites, the small molecules that underpin life, can act as indicators of the physiological state of the body when their abundance varies, offering routes to diagnosis of many diseases. The ability to assay for multiple metabolites simultaneously will underpin a new generation of precision diagnostic tools. Here, we report the development of a handheld device based on complementary metal oxide semiconductor (CMOS) technology with multiple isolated micro-well reaction zones and integrated optical sensing allowing simultaneous enzyme-based assays of multiple metabolites (choline, xanthine, sarcosine and cholesterol) associated with multiple diseases. These metabolites were measured in clinically relevant concentration range with minimum concentrations measured: 25 μM for choline, 100 μM for xanthine, 1.25 μM for sarcosine and 50 μM for cholesterol. Linking the device to an Android-based user interface allows for quantification of metabolites in serum and urine within 2 min of applying samples to the device. The quantitative performance of the device was validated by comparison to accredited tests for cholesterol and glucose.

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.

Monolithic integration of nanophotonic sensors with CMOS detectors can transform the laboratory based nanophotonic sensors into practical devices with a range of applications in everyday life. In this work, by monolithically integrating an array of gold nanodiscs with the CMOS photodiode we have developed a compact and miniaturized nanophotonic sensor system having direct electrical read out. Doing so eliminates the need of expensive and bulky laboratory based optical spectrum analyzers used currently for measurements of nanophotonic sensor chips. The experimental optical sensitivity of the gold nanodiscs is measured to be 275 nm/RIU which translates to an electrical sensitivity of 5.4 V/RIU. This integration of nanophotonic sensors with the CMOS electronics has the potential to revolutionize personalized medical diagnostics similar to the way in which the CMOS technology has revolutionized the electronics industry.

Abstract-Colorimetric, chemiluminescence and refractive index based diagnostics are some of the most important sensing techniques in biomedical science and clinical medicine. Conventionally laboratories and medical clinics rely on bulky and dedicated equipment for each diagnostic technique independently. In this paper, we present CMOS sensor based solutions, comprising a single photon avalanche detector array and photodiode array. The CMOS platform offers low cost integration and wide range of light-based diagnostic techniques, leading to development of point-of-care devices.