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The ability to perform multiple simultaneous protein biomarker measurements in complex media with picomolar sensitivity presents a large challenge to disease diagnostics and fundamental biological studies. Silicon photonic microring resonatom represent a promising platform for real-llme detection of biomolecules on account of their spectral sensitivity toward surface binding events between a target and anti-body-modified microrings. For all refractive index-based sensing schemes, the mass of bound analytes, in combination with other factors such as antibody affinity and surface density, contributes to the observed signal and measurement sensitivity. Therefore, proteins that are simultaneously low in abundance and have a lower molecular weight are often challenging to detect. By employing a more massive secondary antibody to amplify the signal arising from the initial binding event, it is possible to improve both the sensitivity and the specificity of protein assays, allowing for quantitative sensing in complex sample matrices. Herein, a sandwich assay is used to detect the 15.5 kDa human cytoldne intedeuidn-2 (IL-2) at concentrations down to 100 pg/mL (6.5 pM) and to quanfitate unknown solution concentrations over a dynamic range spanning 2.5 orders of magnitude. This same sandwich assay is then used to monitor the temporal secretion profile of IL-2 from Jurkat T lymphocytes in sorum-containing cell culture media in the presence of the entire Jurkat secretome. The same temporal secretion analysis is performed in parallel using a commercial ELISA, revealing similar IL-2 concentration profiles but superior precision for the microring resonator sensing platform. Furthermore, we demonstrate the generality of the sandwich assay methodology on the microring resonator platform for the analysis of any biomolecular target for which two high-affinity antibodies exist by detecting the ~8 kDa cytokine interleukin-8 (IL-8) with a limit of detection and dynamic range similar to that of IL-2. This work demonstrates the first application of silicon photonic microring resonators for detecting cellular secretion of cytokines and represents an important advance for the detection of protein biomarkers on an emerging analytical platform. 10.1021/ac902725q

Because of the inherent complexity of biochemical pathways commonly altered in disease states, it has become accepted that multiplexed analyses can provide a more informative biomolecular understanding of disease onset and progression. Importantly, compared to conventional single-parameter assays, the detailed biomolecular insight gleaned from multiparameter measurements has the potential to greatly improve disease diagnostics, prognostics, and theragnostics. We have previously reported the utility of silicon photonic microring resonators for the sensitive quantitation of a single disease biomarker and herein demonstrate the first example of optical microcavity resonator arrays performing quantitative, label-free, multiplexed analyses of clinically relevant protein biomarkers. In this report, the concentrations of prostate specific antigen (PSA), [alpha]-fetoprotein (AFP), carcinoembryonic antigen (CEA), tumor necrosis factor-[alpha] (TNF-[alpha]), and interleukin-8 (IL-8) are simultaneously determined in three unknown protein cocktail solutions. This letter demonstrates that multiple immunoassays can be performed concurrently on a microresonator platform without any accompanying loss of sensitivity or measurement precision, and therefore, this report lays the groundwork for future applications involving multiplexed analysis of clinically relevant samples. 10.1021/ac902451b

Recent advances in label-free biosensing techniques have shown the potential to simplify clinical analyses. With this motivation in mind, this paper demonstrates for the first time the use of silicon-on-insulator microring optical resonator arrays for the robust and label-free detection of a clinically important protein biomarker in undiluted serum, using carcinoembryonic antigen (CEA) as the test case. We utilize an initial-slope-based quantitation method to sensitively detect CEA at clinically relevant levels and to determine the CEA concentrations of unknown samples in both buffer and undiluted fetal bovine serum. Comparison with a commercial enzyme-linked immunosorbent assay (ELISA) kit reveals that the label-free microring sensor platform has a comparable limit of detection (2 ng/mL) and superior accuracy in the measurement of CEA concentration across a 3 order of magnitude dynamic range. Notably, we report the lowest limit of detection to date for a microring resonator sensor applied to a clinically relevant cancer biomarker. Although this report describes the robust biosensing capabilities of silicon photonic microring resonator arrays for a single parameter assay, future work will focus on utilizing the platform for highly multiplexed, label-free bioanalysis. 10.1021/ac902006p

A real-time deoxyribonucleic acid (DNA) detection method that uses single-strand DNA (ssDNA)-modified nanoparticle probes and micropatterned chemoresponsive diffraction gratings interrogated simultaneously at multiple laser wavelengths is presented. Significant signal amplification is observed due to the use of nanoparticle probe, which is heavily functionalized with ssDNA complementary to target DNA.

Micropatterned polymeric diffraction gratings have been fabricated and evaluated as volatile organic chemical sensors. When operated under nonresonant conditions, sensor elements were found to respond in a rapid (response time 5-15 s) and reproducible fashion to each analyte investigated. Relative response magnitudes were found to be in qualitative agreement with those obtained via surface acoustic wave techniques. Preliminary limits of detection as determined by investigations with micropatterned polyepichlorohydrin, polyisobutytene, and polybutadiene gratings, respectively, were found to be 8, 11, and 7 ppm for toluene, 25, 258; and 72 ppm for methyl ethyl ketone; 41, 102, and 34 ppm for chloroform; and 460, 60, and 59 ppm for hexane. While generally less than 1 order of magnitude higher than those observed for identical polymer/analyte combinations in SAW studies, the observed limits of detection were at or below governmental standards (OSHA-PEL and NIOSH-REL) for each analyte evaluated. These diffraction-based sensors show promise for integration into an array-based sensor system, providing simultaneous identification and quantification of unknown analytes and simple analyte mixtures.

Micropatterning of the vaporchromic charge-transfer salt, [Pt-(CNC6H4C10H21)(sub 4)][Pd(CN)(sub 4)], on transparent platforms yields such structures that behave as transmissive chemoresponsive two-dimensional visible-region diffraction grating or photonic lattices. These lattices are investigated as volatile organic compound (VOC) sensors via a newly devised signal transduction scheme involving diffraction of visible light.

The DNA-encoded antibody libraries (DEAL) method is described for spatially multiplexed detection of ssDNAs and proteins and simultaneous cell sorting, which are all on the same diagnostic platform. The DEAL approach is applied toward the separation of highly complex primary cell mixtures and analysis of protein biomarker panels and it also has the potential to eliminate any adverse effects of sample dilution.

A robust strategy is used for chemically passivating Si(111) surfaces in a method that stabilizes the underlying Si against oxidation and allows for both chemical and electrochemical functionalization of the surface. A two-step chlorination/alkylation procedure is combined with the immobilization of an electroactive benzoquinone molecule on the surface to result in a non-oxidative approach to provide functionality to the silicon surface.