Rapid and sensitive detection of viral nucleic acids using silicon microchips.

Clinical laboratory-based nucleic acid amplification tests (NAT) play an important role in diagnosing viral infections. However, laboratory infrastructure requirements and their failure to diagnose at the point-of-need (PON) limit their clinical utility in both resource-rich and -limited clinical settings. The development of fast and sensitive PON viral NAT may overcome these limitations. The scalability of silicon microchip manufacturing combined with advances in silicon microfluidics present an opportunity for development of rapid and sensitive PON NAT on silicon microchips. In the present study, we present rapid and sensitive NAT for a number of RNA and DNA viruses on the same silicon microchip platform. We first developed sensitive (4 copies per reaction) one-step RT-qPCR and qPCR assays detecting HCV, HIV, Zika, HPV 16, and HPV 18 on a benchtop real-time PCR instrument. A silicon microchip was designed with an etched 1.3 µL meandering microreactor, integrated aluminum heaters, thermal insulation trenches and microfluidic channels; this chip was used in all on-chip experiments. Melting curve analysis confirmed precise and localized heating of the microreactor. Following minimal optimization of reaction conditions, the bench-scale assays were successfully transferred to 1.3 µL silicon microreactors with reaction times of 25 min with no reduction in sensitivity, reproducibility, or reaction efficiencies. Taken together, these results demonstrate that rapid and sensitive detection of multiple viruses on the same silicon microchip platform is feasible. Further development of this technology, coupled with silicon microchip-based nucleic acid extraction solutions, could potentially shift viral nucleic acid detection and diagnosis from centralized clinical laboratories to the PON.

Angled-MMI-based wavelength splitters on silicon nitride waveguide platforms for fluorescence sensing.

Compact wavelength splitters based on angled multimode interferometers (AMMIs) on silicon nitride platforms working in visible lights are reported for fluorescence sensing applications. A diplexer and triplexer with different footprints are designed and experimentally demonstrated. The diplexer and triplexer have the insertion loss of ∼1.7 and ∼2.7 dB/channel with cross talks of less than -22 dB and -17 dB on target wavelengths, respectively. These splitters are used to distinguish the signals collected from two fluorescent dyes that give different emission spectra when excited with an excitation source, due to their different Stokes shifts. In the case of the triplexer, a third port is to collect the excitation light, both to monitor the remaining excitation power and to reduce the interference at the signal ports. A termination structure at the end of the AMMIs and input and output tapering waveguides as a part of the wavelength splitters are designed and their performances are presented.

Observation of nanoscale adhesion, friction and wear between ALD Al2O3 coated silicon MEMS sidewalls.

We report a novel investigation of the tribological properties of aluminum oxide (Al2O3) when it is used as protective coating on the sidewalls of microelectromechanical systems (MEMS). By using an in-house built optical displacement measurement system, we were able to measure the on-chip displacements with an unprecedented resolution of 2 nm. This corresponds to 2 nN and 9 nN force resolution, respectively, depending on whether an adhesion or a friction sensor MEMS device was used for the measurement. Al2O3 was deposited on the vertical etched sidewalls using atomic layer deposition (ALD). All tests were carried out in ambient conditions. The same tests carried out on uncoated polysilicon devices were not reproducible due to stiction, which sometimes prevented the interacting surfaces from moving once contact was made. The higher adhesion of silicon was also found to hinder the mobility of the slider. In the ALD-coated devices, we observed increasing adhesion after 50000 repeated contacts. We attribute this increase to the accumulation of aluminum hydroxide debris produced by the reaction with moisture in the environment. We also investigated the long-term effect of friction on the coated silicon sidewalls. The dissipated energy decreases, with a minimum lateral force occurring around the 1000th cycle. After 1000 cycles, the lateral displacement decreases, suggesting an additional lateral dragging force caused by the interaction between a mixture of aluminum hydroxides and water. However, the small overall amount of debris produced during the friction test indicates the outstanding characteristic of Al2O3 as a protective coating for MEMS that use contacting or sliding interfaces.