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.

Interfacing neural cells with typical microelectronics materials for future manufacturing.

The biocompatibility of materials used in electronic devices is critical for the development of implantable devices like pacemakers and neuroprosthetics, as well as in future biomanufacturing. Biocompatibility refers to the ability of these materials to interact with living cells and tissues without causing an adverse response. Therefore, it is essential to evaluate the biocompatibility of metals and semiconductor materials used in electronic devices to ensure their safe use in medical applications.

Lithographically patterned micro-nozzles for controlling fluid flow profiles for drug delivery and in vitro imaging applications.

Precisely controlling delivery of drugs and other reagents is important for intravital microscopy studies. In this work, photolithographic integration of micro-nozzles onto a microfluidic platform was performed to tune the fluid flow profile and depth of penetration into biological tissue mimics. Performance characteristics were measured by correlating the flow rate through the device to the applied pressure and/or delivery of dyes into solution and agarose gel-based phantom tissue.

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.

Multiplexed detection and quantification of human antibody response to COVID-19 infection using a plasmon enhanced biosensor platform.

The 2019 SARS CoV-2 (COVID-19) pandemic has illustrated the need for rapid and accurate diagnostic tests. In this work, a multiplexed grating-coupled fluorescent plasmonics (GC-FP) biosensor platform was used to rapidly and accurately measure antibodies against COVID-19 in human blood serum and dried blood spot samples. The GC-FP platform measures antibody-antigen binding interactions for multiple targets in a single sample, and has 100% selectivity and sensitivity (n = 23) when measuring serum IgG levels against three COVID-19 antigens (spike S1, spike S1S2, and the nucleocapsid protein).

Surface Enhanced Raman Spectroscopy for Single Molecule Protein Detection.

A two-step process of protein detection at a single molecule level using SERS was developed as a proof-of-concept platform for medical diagnostics. First, a protein molecule was bound to a linker in the bulk solution and then this adduct was chemically reacted with the SERS substrate. Traut's Reagent (TR) was used to thiolate Bovine serum albumin (BSA) in solution followed by chemical cross linking to a gold surface through a sulfhydryl group.

A Dynamic Culture Method to Produce Ovarian Cancer Spheroids under Physiologically-Relevant Shear Stress.

The transcoelomic metastasis pathway is an alternative to traditional lymphatic/hematogenic metastasis. It is most frequently observed in ovarian cancer, though it has been documented in colon and gastric cancers as well. In transcoelomic metastasis, primary tumor cells are released into the abdominal cavity and form cell aggregates known as spheroids.

Self-Balancing Position-Sensitive Detector (SBPSD).

Optical position-sensitive detectors (PSDs) are a non-contact method of tracking the location of a light spot. Silicon-based versions of such sensors are fabricated with standard CMOS technology, are inexpensive and provide a real-time, analog signal output corresponding to the position of the light spot. An innovative type of optical position sensor was developed using two back-to-back connected photodiodes.

Direct attachment of DNA to semiconducting surfaces for biosensor applications.

In this work we propose a novel method of immobilizing nucleic acids for field effect or high electron mobility transistor-based biosensors. The naturally occurring 5' terminal phosphate group on nucleic acids was used to coordinate with semiconductor and metal oxide surfaces. We demonstrate that DNA can be directly immobilized onto ZrO(2), AlGaN, GaN, and HfO(2) while retaining its ability to hybridize to target sequences with high specificity.

A living cell-based biosensor utilizing G-protein coupled receptors: principles and detection methods.

This study explores the feasibility of using a bullfrog fibroblast cell line (FT cells) expressing G protein coupled receptors (GPCRs) as the basis for a living cell-based biosensor. We have fabricated gold microelectrode arrays on a silicon dioxide substrate that supports long term, robust growth of the cells at room temperature and under ambient atmospheric conditions. Activation of an endogenous GPCR to ATP was monitored with an optical method that detects rises in intracellular calcium and with an electrochemical method that monitors the increased secretion of pre-loaded norepinephrine on a MEMS device.

Amperometric detection of quantal catecholamine secretion from individual cells on micromachined silicon chips.

We have fabricated electrochemical electrodes in picolitersized wells for measuring catecholamine release from individual cells with millisecond resolution. Each well-electrode roughly conforms to the shape of the cell in order to capture a large fraction of released catecholamine with high time resolution. Using this device, we can resolve spikes in amperometric current corresponding to quantal catecholamine release via exocytosis.