A Multiplex "Disposable Photonics" Biosensor Platform and Its Application to Antibody Profiling in Upper Respiratory Disease.

Photonic technologies promise to deliver quantitative, multiplex, and inexpensive medical diagnostic platforms by leveraging the highly scalable processes developed for the fabrication of semiconductor microchips. However, in practice, the affordability of these platforms is limited by complex and expensive sample handling and optical alignment. We previously reported the development of a disposable photonic assay that incorporates inexpensive plastic micropillar microfluidic cards for sample delivery. That system as developed was limited to singleplex assays due to its optical configuration. To enable multiplexing, we report a new approach addressing multiplex light I/O, in which the outputs of individual grating couplers on a photonic chip are mapped to fibers in a fiber bundle. As demonstrated in the context of detecting antibody responses to influenza and SARS-CoV-2 antigens in human serum and saliva, this enables multiplexing in an inexpensive, disposable, and compact format.

Biosensing with Silicon Nitride Microring Resonators Integrated with an On-Chip Filter Bank Spectrometer.

Wearable, mobile, and point-of-care (POC) sensors comprise a rapidly expanding field of devices aimed at improving human health by relaying real-time biometric data such as heart rate and glucose levels. The current scope of what these devices can offer healthcare is limited by their inability to measure biomarkers associated with inflammation, well-being, and disease. Photonic biosensors that integrate sensing elements directly with spectrometers, lasers, and detectors are an attractive approach to enabling POC sensors, with distinct advantages in terms of size, weight, power consumption, and cost. Here, we have demonstrated for the first time the integration of photonic microring resonator biosensors with an on-chip microring filter bank spectrometer for the controlled detection of inflammatory biomarker C-reactive protein (CRP) in serum. We demonstrate that sensor and spectrometer performance is tolerant of temperature variation, as temperature dependence moves in parallel. Finally, we assess the impact of manufacturing variability on the 300 mm wafer scale on the performance of the spectrometer. Taken together, these results suggest that integration of on-chip ring filter bank spectrometers with ring resonator-based biosensors constitutes an attractive approach toward cost-effective integrated sensor development.

A photonic biosensor-integrated tissue chip platform for real-time sensing of lung epithelial inflammatory markers.

Tissue chip (TC) devices, also known as microphysiological systems (MPS) or organ chips (OCs or OoCs), seek to mimic human physiology on a small scale. They are intended to improve upon animal models in terms of reproducibility and human relevance, at a lower monetary and ethical cost. Virtually all TC systems are analyzed at an endpoint, leading to widespread recognition that new methods are needed to enable sensing of specific biomolecules in real time, as they are being produced by the cells. To address this need, we incorporated photonic biosensors for inflammatory cytokines into a model TC. Human bronchial epithelial cells seeded in a microfluidic device were stimulated with lipopolysaccharide, and the cytokines secreted in response sensed in real time. Sensing analyte transport through the TC in response to disruption of tissue barrier was also demonstrated. This work demonstrates the first application of photonic sensors to a human TC device, and will enable new applications in drug development and disease modeling.

Disposable photonics for cost-effective clinical bioassays: application to COVID-19 antibody testing.

Decades of research have shown that biosensors using photonic circuits fabricated using CMOS processes can be highly sensitive, selective, and quantitative. Unfortunately, the cost of these sensors combined with the complexity of sample handling systems has limited the use of such sensors in clinical diagnostics. We present a new "disposable photonics" sensor platform in which rice-sized (1 × 4 mm) silicon nitride ring resonator sensor chips are paired with plastic micropillar fluidic cards for sample handling and optical detection. We demonstrate the utility of the platform in the context of detecting human antibodies to SARS-CoV-2, both in convalescent COVID-19 patients and for subjects undergoing vaccination. Given its ability to provide quantitative data on human samples in a simple, low-cost single-use format, we anticipate that this platform will find broad utility in clinical diagnostics for a broad range of assays.

Array-based analysis of SARS-CoV-2, other coronaviruses, and influenza antibodies in convalescent COVID-19 patients.

Detection of antibodies to upper respiratory pathogens is critical to surveillance, assessment of the immune status of individuals, vaccine development, and basic biology. The urgent need for antibody detection tools has proven particularly acute in the COVID-19 era. We report a multiplex label-free antigen microarray on the Arrayed Imaging Reflectometry (AIR) platform for detection of antibodies to SARS-CoV-2, SARS-CoV-1, MERS, three circulating coronavirus strains (HKU1, 229E, OC43) and three strains of influenza. We find that the array is readily able to distinguish uninfected from convalescent COVID-19 subjects, and provides quantitative information about total Ig, as well as IgG- and IgM-specific responses.