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.

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.

Dielectrophoretic Nanoparticle Aggregation for On-Demand Surface Enhanced Raman Spectroscopy Analysis.

Rapid chemical identification of drugs of abuse in biological fluids such as saliva is of growing interest in healthcare and law enforcement. Accordingly, a label-free detection platform that accepts biological fluid samples is of great practical value. We report a microfluidics-based dielectrophoresis-induced surface enhanced Raman spectroscopy (SERS) device, which is capable of detecting physiologically relevant concentrations of methamphetamine in saliva in under 2 min. In this device, iodide-modified silver nanoparticles are trapped and released on-demand using electrodes integrated in a microfluidic channel. Principal component analysis (PCA) is used to reliably distinguish methamphetamine-positive samples from the negative control samples. Passivation of the electrodes and flow channels minimizes microchannel fouling by nanoparticles, which allows the device to be cleared and reused multiple times.

Discrete free-surface millifluidics for rapid capture and analysis of airborne molecules using surface-enhanced Raman spectroscopy.

A lithography-free, low-cost, free-surface millifluidic device is reported using discrete liquid interfaces for capturing and detecting gas-phase analyte molecules at low partial pressures out of a gas flow of time-varying composition. The architecture, based on segmented flow, consists of alternating regions of liquid and gas wherein the liquid regions contain surface-enhanced Raman spectroscopy (SERS)-active silver nanoparticles, while the gas regions contain trace quantities of vapor-phase analyte, thereby controlling and optimizing transport and mixing of the gas-phase analyte with the liquid phase. Once absorbed in the liquid phase, the entrained analyte molecules induce aggregation of the aqueous silver nanoparticles. The resulting aggregates consisting of nanoparticles and adsorbed analyte molecules produce intense SERS spectra that reliably identify the absorbed analyte in real time. The approach can be used to determine the time-variable trace chemical composition of a gas stream with applications in, for example, environmental monitoring and online industrial process monitoring, or as a SERS-based detector following gas chromatographic separation. The operation of the system is demonstrated using 4-aminobenzenethiol vapor at 750 ppb, and the detection response time is <2 min.

Free-surface microfluidics/surface-enhanced Raman spectroscopy for real-time trace vapor detection of explosives.

The dominant physical transport processes are analyzed in a free-surface microfluidic and surface-enhanced Raman spectroscopy (SERS) chemical detection system. The analysis describes the characteristic fluid dynamics and mass transport effects occurring in a microfluidic detection system whose analyte absorption and concentration capability is designed to operate on principles inspired by canine olfaction. The detection system provides continuous, real-time monitoring of particular vapor-phase analytes at concentrations of 1 ppb. The system is designed with a large free-surface-to-volume ratio microfluidic channel which allows for polar or hydrophilic airborne analytes to readily be partitioned from the surrounding gas phase into the aqueous phase for detection. The microfluidic stream can concentrate certain molecules by up to 6 orders of magnitude, and SERS can enhance the Raman signal by 9-10 orders of magnitude for molecules residing in the so-called SERS "hot spots", providing extremely high detection sensitivity. The resulting vibrational spectra are sufficiently specific to identify the detected analyte unambiguously. Detection performance was demonstrated using a nominal 1 ppb, 2,4-dinitrotoluene (2,4-DNT) vapor stream entrained within N(2) gas. Applications to homeland security arise from the system's high sensitivity and its ability to provide highly reproducible, continuous chemical detection monitoring with minimal sampling requirements.

Photoreduction at a distance: facile, nonlocal photoreduction of Ag ions in solution by plasmon-mediated photoemitted electrons.

Surface-immobilized, densely packed gold nanoparticles in contact with aqueous silver ions and exposed to red light rapidly photoreduce silver ions in solution producing radially symmetric metal deposits with diameters many times larger than the diameter of the illuminating laser beam. The average particle sizes in the deposit increase with radial distance from the center of the deposit. This reduction-at-a-distance effect arises from surface-plasmon-mediated photoemission, with the photoemitted electrons conducting along percolating silver pathways, reducing silver ions along these conducting channels and especially at their periphery, thereby propagating the effect of the illuminating laser outward.

Free-surface microfluidic control of surface-enhanced Raman spectroscopy for the optimized detection of airborne molecules.

We present a microfluidic technique for sensitive, real-time, optimized detection of airborne water-soluble molecules by surface-enhanced Raman spectroscopy (SERS). The method is based on a free-surface fluidic device in which a pressure-driven liquid microchannel flow is constrained by surface tension. A colloidal suspension of silver nanoparticles flowing through the microchannel that is open to the atmosphere absorbs gas-phase 4-aminobenzenethiol (4-ABT) from the surrounding environment. As surface ions adsorbed on the colloid nanoparticles are substituted by 4-ABT, the colloid aggregates, forming SERS "hot spots" whose concentrations vary predictably along the microchannel flow. 4-ABT confined in these hot spots produces SERS spectra of very great intensity. An aggregation model is used to account quantitatively for the extent of colloid aggregation as determined from the variation of the SERS intensity measured as a function of the streamwise position along the microchannel, which also corresponds to nanoparticle exposure time. This allows us to monitor simultaneously the nanoparticle aggregation process and to determine the location at which the SERS signal is optimized.

A reagentless signal-on architecture for electronic, aptamer-based sensors via target-induced strand displacement.

Thrombin binding stabilizes the alternative G-quadruplex conformation of the aptamer, liberating the methylene blue (MB)-tagged oligonucleotide to produce a flexible, single-stranded DNA element. This allows the MB tag to collide with the gold electrode surface, producing a readily detectable Faradaic current at thrombin concentrations as low as approximately 3 nM.