We demonstrate the capabilities of the SiPhox Home platform to measure blood biomarker concentrations such as a highsensitivity C-reactive protein (hsCRP) assay. The system consists of disposable biosensor cartridges which plug into a compact reader instrument. The reader contains a miniature low-cost swept-source laser and detection system which is designed to interrogate on-chip resonant or interferometric sensors, and we demonstrate excellent performance of manufactured readers compared to a gold-standard laboratory tunable laser. The cartridge includes a silicon photonics chip with 15 individually addressable microring resonator sensors which transduce molecular binding into a wavelength shift measured by the reader. We demonstrate both labeled and label-free ring resonator immunoassays running on our platform which can measure the relevant hsCRP concentration range of 0.2 – 10 μg/mL. In a preliminary method comparison study, 7 volunteers measured their hsCRP values at home by two methods: SiPhox Home, which displays results after only a 4-minute run time, and a commercially available mail-in blood test, which typically returns results in 3-5 business days. The results show a good correlation and demonstrate the potential for high-quality at-home measurement of blood biomarkers using manufacturable silicon photonics technology.
The advent of the SARS-CoV-2 pandemic has rekindled the demand for inexpensive, point-of-care and at-home diagnostic systems that offer high degrees of scalability, sensitivity, and specificity. While several options of sensing modalities have been researched and subsequently commercialized, these sensing systems are yet to simultaneously satisfy the spiked demand for higher accuracy and scalable manufacturing. In this context, the prospect of integrated photonics-enabled biosensors has garnered immense attention from both scientific and business communities. However, realizing low group indices of the photonic structures required for higher bulk sensitivities at commonly used telecom operation wavelengths is typically achieved using design approaches incompatible with foundry process constraints. Siphox Inc., founded in 2020, developed an ensemble biosensing platform by merging the benefits of CMOS-friendly integrated photonic structures with proprietary biochemical assays to realize low-cost, highly sensitive, label and label-free, multiplexed diagnostic system. As a first demonstration, we present our results of 15-plex biosensing utilizing low-loss (<3.5dB/cm) Si3N4 strip-waveguide ring resonators fabricated using 248 nm deep UV (DUV) stepper lithography. We describe the design, simulation, and measurement results of bulk and surface sensitivities and detection limits for our TE-polarized waveguide resonator structures operating at O-band (1310 nm). We demonstrate a bulk sensitivity of >117 nm/RIU and an intrinsic limit of detection of 1.87×10−4 RIU.
Micro-ring resonators have emerged as a powerful platform for analyzing and detecting biomolecules at low concentrations. Here we demonstrate a high contrast cleavage detection (HCCD) assay on a micro-ring resonator to sense the cleavage of DNA reporterslinked to high-contrast nanoparticles (NPs), leading to dramatic optical signal amplification. The HCCD mechanism is coupled with a CRISPR-Cas12a assay for rapid and sensitive on-chip nucleic acid detection. Leveraging high-contrast gold nanoparticle (AuNP) reporters, an ~8 nm resonance shift is observed by using a 1 nM of complementary DNA (cDNA) target, matching part of the SARS-CoV-2 sequence. In addition, we show that a micro-ring resonator can not only record the entire surface functionalization process, as has been show previously, but also monitor CRISPR reactions in-situ. This work is the first step toward novel nucleic acid amplification-free detection via a combination of integrated photonics and CRISPR-Cas collateral cleavage assays.
We demonstrate operation of an interferometric optical gyroscope that uses an on-chip 3m ultra-low-loss silicon nitride waveguide coil. The measured minimum waveguide loss of the waveguide coil fabricated using lithographic die stitching was 0.78 dB/m. The angle random walk and bias instability of the gyroscope were characterized to be 8.52 deg/hr1/2 and 58.7 deg/hr respectively.
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