A robust silicon photonic platform for multiparameter biological analysis

Abstract

Silicon photonic technology has incredible potential to transform multiplexed bioanalysis on account of the scalability of device fabrication, which maps favorably to a myriad of medical diagnostic applications. The optical properties of CMOS-fabricated microring resonators are incredibly responsive to changes in the local dielectric environment accompanying a biological binding event near the ring surface. Arrays of high-Q microrings were designed to be individually addressable both in surface derivitization, using well-established microarraying technologies, and in optical evaluation. The optical response of each ring can be determined in near real time allowing multiple biomolecular interactions to be simultaneously monitored. We describe a stable and robust measurement platform that allows sensitive visualization of small molecule surface chemical derivitization as well as monitoring of biological interactions, including the detection of proteins and nucleic acids. We also present recent results demonstrating multiplexed measurement of cancer markers. These demonstrations establish a pathway to higher level multiparameter analysis from real-world patient samples; a development that will enable individualized disease diagnostics and personalized medicine.

Nucleic acid detection technologies and marker molecules in bacterial diagnostics

“…Microring resonators are highly reproducible, scalable and cost-effective alternatives to other traditional optical sensing technologies due to their easy fabrication process via commercially available semiconductor processing methods. Furthermore, microring sensors require optical technology that is already commonly available in telecommunications, reducing the need for expensive hardware development [73]. Current state-of-the-art technology enables simultaneous monitoring and analysis of 128 different positions in a single microring resonator chip assay [74].…”

Silicon Photonics: A Review of Recent Literature

“…Several bio-sensing techniques are coming into prominence, such as the use of photonic crystals, surface-plasmon resonances, microfluidics, ring resonators, interferometers, grating couplers, evanescent fields in silicon photonic-wire waveguides, and spectroscopy in a silicon labon-a-chip. Representative 2009 publications for those approaches are [64][65][66][67][68][69][70][71].…”

Interferometric Methods for Label-Free Molecular Interaction Studies

“…12,17–20 The fluorescence signal generated by labeling may also be sensitive to perturbations by local field intensity, pH, and temperature, may be subject to bleaching and quenching, and may suffer from false positives due to background binding and/or autofluorescence of compounds. 12,21 Heterogeneity of fluorescent labeling is also a significant challenge, 20,22 presenting particular difficulty in quantifying binding energy and expression levels with confidence and reproducibility in microarray formats. 23 Furthermore, prior knowledge of the target molecule is necessary to incorporate labeling.…”

“…The group continues to expand their work to multiplex sensor chips by putting 4 different proteins on a single sensor, although initial crosstalk has been observed in their preliminary experiments. 22 Recent work has applied this technology to the study of microRNAs, allowing for the distinction of single nucleotide polymorphisms and quantitation down to an amount of 150 fmol. 57 This technology is being commercialized by Genalyte Inc., San Diego, CA, (http://www.genalyte.com/), which is a late-stage start-up company that, at the time of this Review, is soliciting collaborations for the third generation technology.…”