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Label-free detection of single protein using a nanoplasmonic-photonic hybrid microcavity. - Nano letters
Recently we reported the detection and sizing of the smallest RNA virus MS2 with a mass of 6 ag from the resonance frequency shift of a whispering gallery mode-nanoshell hybrid resonator (WGM-h) upon adsorption on the nanoshell and anticipated that single protein above 0.4 ag should be detectable but with considerably smaller signals. Here, we report the detection of single thyroid cancer marker (Thyroglobulin, Tg) and bovine serum albumin (BSA) proteins with masses of only 1 ag and 0.11 ag (66 kDa), respectively. However, the wavelength shifts are enhanced beyond those anticipated in our earlier work by 240% for Tg and 1500% for BSA. This surprising sensitivity is traced to a short-range reactive field near the surface of our Au nanoshell receptor due to intrinsic random bumps of protein size, leading to an unanticipated increase in sensitivity to single protein, which grows larger as the protein diminishes in size. As a consequence of the largest signal-to-noise ratio in our BSA experiments (S/N â‰ˆ 13), we conservatively estimated a new protein limit of detection for our WGM-h of 5 kDa.
Periodic plasmonic enhancing epitopes on a whispering gallery mode biosensor. - Optics express
We propose the attachment of a periodic array of gold nanoparticles (epitopes) to the equator of a Whispering Gallery Mode Biosensor for the purpose of plasmonically enhancing nanoparticle sensing in a self-referencing manner while increasing the capture rate of analyte to antibodies attached to these plasmonic epitopes. Our approach can be applied to a variety of whispering gallery mode resonators from silicon/silica rings and disks to capillaries. The interpretation of the signals is particularly simple since the optical phase difference between the epitopes is designed to be an integer multiple of ?, allowing the wavelength shift from each binding event to add independently.
Bioinspired optofluidic FRET lasers via DNA scaffolds. - Proceedings of the National Academy of Sciences of the United States of America
Optofluidic dye lasers hold great promise for adaptive photonic devices, compact and wavelength-tunable light sources, and micro total analysis systems. To date, however, nearly all those lasers are directly excited by tuning the pump laser into the gain medium absorption band. Here we demonstrate bioinspired optofluidic dye lasers excited by FRET, in which the donor-acceptor distance, ratio, and spatial configuration can be precisely controlled by DNA scaffolds. The characteristics of the FRET lasers such as spectrum, threshold, and energy conversion efficiency are reported. Through DNA scaffolds, nearly 100% energy transfer can be maintained regardless of the donor and acceptor concentration. As a result, efficient FRET lasing is achieved at an unusually low acceptor concentration of micromolar, over 1,000 times lower than that in conventional optofluidic dye lasers. The lasing threshold is on the order of Î¼J/mm(2). Various DNA scaffold FRET lasers are demonstrated to illustrate vast possibilities in optofluidic laser designs. Our work opens a door to many researches and applications such as intracavity bio/chemical sensing, biocontrolled photonic devices, and biophysics.
Functionalized Ga2O3 nanowires as active material in room temperature capacitance-based gas sensors. - Langmuir : the ACS journal of surfaces and colloids
We report the first evidence for functionalization of Ga(2)O(3) nanowires (NWs), which have been incorporated as the active material in room temperature capacitance gas-sensing devices. An adsorbed layer of pyruvic acid (PA) was successfully formed on Ga(2)O(3) NWs by simple room temperature vapor transport, which was confirmed by Fourier transform infrared spectroscopy. The effect of the adsorbed PA on the surface properties was demonstrated by the change in the response of the NW gas-sensing devices. Results indicate that the adsorption of PA reduced the sensitivity of the Ga(2)O(3) NW device to common hydrocarbons such as nitromethane and acetone while improving the response to triethylamine by an order of magnitude. Taking into account the simplicity of this functionalization together with the ease of producing these capacitance-based gas-sensing devices, this approach represents a viable technique for sensor development.
Acoustic lens characterization for ultrasound and photoacoustic C-scan imaging modalities. - Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference
From a fundamental perspective, image reconstruction tasks in both ultrasound pulse echo and photoacoustic imaging are identical. We propose a C-scan imaging scheme that is applicable to both modalities where the image reconstruction is achieved through focusing action of an acoustic lens. The theory to characterize the imaging system is presented. Experimental methodology to determine the system point-spread-function is outlined and demonstrated with preliminary results.
Whispering-gallery-mode biosensing: label-free detection down to single molecules. - Nature methods
Optical label-free detectors, such as the venerable surface plasmon resonance (SPR) sensor, are generally favored for their ability to obtain quantitative data on intermolecular binding. However, before the recent introduction of resonant microcavities that use whispering gallery mode (WGM) recirculation, sensitivity to single binding events had not materialized. Here we describe the enhancement mechanisms responsible for the extreme sensitivity of the WGM biosensor, review its current implementations and applications, and discuss its future possibilities.
High-Q microsphere biosensor - analysis for adsorption of rodlike bacteria. - Optics express
Theory is developed for frequency shift and linewidth-broadening induced by rodlike bacteria bound to micro-optical resonators. Optical shift of whispering gallery modes (WGMs) is modeled by introducing a form factor that accounts for random horizontal orientation of cylindrical bacteria bound by their high refractive index cell walls. Linewidth-broadening is estimated from scattering losses. Analytic results are confirmed by measurement using E.Coli as model system (~10(2) bacteria/mm(2) sensitivity), establishing the WGM biosensor as sensitive technique for detection and analysis of micro-organisms.
Identification of BRCA1 missense substitutions that confer partial functional activity: potential moderate risk variants? - Breast cancer research : BCR
Many of the DNA sequence variants identified in the breast cancer susceptibility gene BRCA1 remain unclassified in terms of their potential pathogenicity. Both multifactorial likelihood analysis and functional approaches have been proposed as a means to elucidate likely clinical significance of such variants, but analysis of the comparative value of these methods for classifying all sequence variants has been limited.We have compared the results from multifactorial likelihood analysis with those from several functional analyses for the four BRCA1 sequence variants A1708E, G1738R, R1699Q, and A1708V.Our results show that multifactorial likelihood analysis, which incorporates sequence conservation, co-inheritance, segregation, and tumour immunohistochemical analysis, may improve classification of variants. For A1708E, previously shown to be functionally compromised, analysis of oestrogen receptor, cytokeratin 5/6, and cytokeratin 14 tumour expression data significantly strengthened the prediction of pathogenicity, giving a posterior probability of pathogenicity of 99%. For G1738R, shown to be functionally defective in this study, immunohistochemistry analysis confirmed previous findings of inconsistent 'BRCA1-like' phenotypes for the two tumours studied, and the posterior probability for this variant was 96%. The posterior probabilities of R1699Q and A1708V were 54% and 69%, respectively, only moderately suggestive of increased risk. Interestingly, results from functional analyses suggest that both of these variants have only partial functional activity. R1699Q was defective in foci formation in response to DNA damage and displayed intermediate transcriptional transactivation activity but showed no evidence for centrosome amplification. In contrast, A1708V displayed an intermediate transcriptional transactivation activity and a normal foci formation response in response to DNA damage but induced centrosome amplification.These data highlight the need for a range of functional studies to be performed in order to identify variants with partially compromised function. The results also raise the possibility that A1708V and R1699Q may be associated with a low or moderate risk of cancer. While data pooling strategies may provide more information for multifactorial analysis to improve the interpretation of the clinical significance of these variants, it is likely that the development of current multifactorial likelihood approaches and the consideration of alternative statistical approaches will be needed to determine whether these individually rare variants do confer a low or moderate risk of breast cancer.
Coupled whispering gallery modes in a multilayer-coated microsphere. - Optics letters
Whispering gallery modes in a microsphere coated with three layers of high, low, and high refractive indices (RIs) are considered. Coastal modes and inland modes, centered on the outer and inner high-RI layers, exist as different radial modes. At right values of RI and thickness of the three layers, an inland mode and a coastal mode couple to produce a radial distribution of the photonic field that resembles bonding and antibonding orbitals. The coupling occurs across a layer of the middle low-RI layer, much thicker than the wavelength of light. The coupling is analyzed in a quantum-mechanical analog of a one-dimensional particle in a double-well potential.
Detection of protein orientation on the silica microsphere surface using transverse electric/transverse magnetic whispering gallery modes. - Biophysical journal
The state of adsorbed protein molecules can be examined by comparing the shifts in a narrow line resonance wavelength of transverse electric (TE) and transverse magnetic (TM) whispering gallery modes (WGM) when the molecules adsorb onto a transparent microsphere that houses WGM. In adsorption of bovine serum albumin (BSA) onto an aminopropyl-modified silica microsphere, the TM/TE shift ratio indicated highly anisotropic polarizability of BSA in the direction normal to the surface, most likely ascribed to anchoring the heart-shaped protein molecule by one of its tips. The polarization-dependent resonance shift was confirmed when the surrounding refractive index was uniformly changed by adding salt, which would simulate adsorption of large objects.
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