A digital microarray using interferometric detection of plasmonic nanorod labels

DNA and protein microarrays are a high-throughput technology that allow the simultaneous quantification of tens of thousands of different biomolecular species. The mediocre sensitivity and dynamic range of traditional fluorescence microarrays compared to other techniques have been the technology's Achilles' Heel, and prevented their adoption for many biomedical and clinical diagnostic applications. Previous work to enhance the sensitivity of microarray readout to the single-molecule ('digital') regime have either required signal amplifying chemistry or sacrificed throughput, nixing the platform's primary advantages. Here, we report the development of a digital microarray which extends both the sensitivity and dynamic range of microarrays by about three orders of magnitude. This technique uses functionalized gold nanorods as single-molecule labels and an interferometric scanner which can rapidly enumerate individual nanorods by imaging them with a 10x objective lens. This approach does not require any chemical enhancement such as silver deposition, and scans arrays with a throughput similar to commercial fluorescence devices. By combining single-nanoparticle enumeration and ensemble measurements of spots when the particles are very dense, this system achieves a dynamic range of about one million directly from a single scan

A digital microarray using interferometric detection of plasmonic nanorod labels

DNA and protein microarrays are a high-throughput technology that allow the simultaneous quantification of tens of thousands of different biomolecular species. The mediocre sensitivity and dynamic range of traditional fluorescence microarrays compared to other techniques have been the technology's Achilles' Heel, and prevented their adoption for many biomedical and clinical diagnostic applications. Previous work to enhance the sensitivity of microarray readout to the single-molecule ('digital') regime have either required signal amplifying chemistry or sacrificed throughput, nixing the platform's primary advantages. Here, we report the development of a digital microarray which extends both the sensitivity and dynamic range of microarrays by about three orders of magnitude. This technique uses functionalized gold nanorods as single-molecule labels and an interferometric scanner which can rapidly enumerate individual nanorods by imaging them with a 10x objective lens. This approach does not require any chemical enhancement such as silver deposition, and scans arrays with a throughput similar to commercial fluorescence devices. By combining single-nanoparticle enumeration and ensemble measurements of spots when the particles are very dense, this system achieves a dynamic range of about one million directly from a single scan.First author draf

Digital microarrays: single-molecule readout with interferometric detection of plasmonic nanorod labels

DNA and protein microarrays are a high-throughput technology that allow the simultaneous quantification of tens of thousands of different biomolecular species. The mediocre sensitivity and limited dynamic range of traditional fluorescence microarrays compared to other detection techniques have been the technology’s Achilles’ heel and prevented their adoption for many biomedical and clinical diagnostic applications. Previous work to enhance the sensitivity of microarray readout to the single-molecule (“digital”) regime have either required signal amplifying chemistry or sacrificed throughput, nixing the platform’s primary advantages. Here, we report the development of a digital microarray which extends both the sensitivity and dynamic range of microarrays by about 3 orders of magnitude. This technique uses functionalized gold nanorods as single-molecule labels and an interferometric scanner which can rapidly enumerate individual nanorods by imaging them with a 10× objective lens. This approach does not require any chemical signal enhancement such as silver deposition and scans arrays with a throughput similar to commercial fluorescence scanners. By combining single-nanoparticle enumeration and ensemble measurements of spots when the particles are very dense, this system achieves a dynamic range of about 6 orders of magnitude directly from a single scan. As a proof-of-concept digital protein microarray assay, we demonstrated detection of hepatitis B virus surface antigen in buffer with a limit of detection of 3.2 pg/mL. More broadly, the technique’s simplicity and high-throughput nature make digital microarrays a flexible platform technology with a wide range of potential applications in biomedical research and clinical diagnostics.The authors wish to thank Oguzhan Avci and Jacob Trueb for thoughtful comments and suggestions regarding numerical optimization of the optical system. This work was funded in part by a research contract with ASELSAN, Inc. and the Wallace H. Coulter Foundation 2010 Coulter Translational Award. (ASELSAN, Inc.; Wallace H. Coulter Foundation Coulter Translational Award)Accepted manuscrip

Interferometric detection and enumeration of viral particles using Si-based microfluidics

Single-particle interferometric reflectance imaging sensor enables optical visualization and characterization of individual nanoparticles without any labels. Using this technique, we have shown end-point and real-time detection of viral particles using laminate-based active and passive cartridge configurations. Here, we present a new concept for low-cost microfluidic integration of the sensor chips into compact cartridges through utilization of readily available silicon fabrication technologies. This new cartridge configuration will allow simultaneous detection of individual virus binding events on a 9-spot microarray, and provide the needed simplicity and robustness for routine real-time operation for discrete detection of viral particles in a multiplex format.This work was supported in part by a research contract with the ASELSAN Research Center, Ankara, Turkey, and in part by the European Union's Horizon 2020 FET Open program under Grant 766466-INDEX. (ASELSAN Research Center, Ankara, Turkey; 766466-INDEX - European Union's Horizon 2020 FET Open program)First author draf

Photonic bandgap narrowing in conical hollow core Bragg fibers

Cataloged from PDF version of article.We report the photonic bandgap engineering of Bragg fibers by controlling the thickness profile of the fiber during the thermal drawing. Conical hollow core Bragg fibers were produced by thermal drawing under a rapidly alternating load, which was applied by introducing steep changes to the fiber drawing speed. In conventional cylindrical Bragg fibers, light is guided by omnidirectional reflections from interior dielectric mirrors with a single quarter wave stack period. In conical fibers, the diameter reduction introduced a gradient of the quarter wave stack period along the length of the fiber. Therefore, the light guided within the fiber encountered slightly smaller dielectric layer thicknesses at each reflection, resulting in a progressive blueshift of the reflectance spectrum. As the reflectance spectrum shifts, longer wavelengths of the initial bandgap cease to be omnidirectionally reflected and exit through the cladding, which narrows the photonic bandgap. A narrow transmission bandwidth is particularly desirable in hollow waveguide mid-infrared sensing schemes, where broadband light is coupled to the fiber and the analyte vapor is introduced into the hollow core to measure infrared absorption. We carried out sensing simulations using the absorption spectrum of isopropyl alcohol vapor to demonstrate the importance of narrow bandgap fibers in chemical sensing applications. © 2014 AIP Publishing LLC

Elastic electron scattering by laser-excited 138Ba( ... 6s6p 1P1) atoms

The results of a joint experimental and theoretical study concerning elastic electron scattering by laser-excited 138Ba( ... 6s6p 1P1) atoms are described. These studies demonstrate several important aspects of elastic electron collisions with coherently excited atoms, and are the first such studies. From the measurements, collision and coherence parameters, as well as cross sections associated with an atomic ensemble prepared with an arbitrary in-plane laser geometry and linear polarization (with respect to the collision frame), or equivalently with any magnetic sublevel superposition, have been obtained at 20 eV impact energy and at 10°, 15° and 20° scattering angles. The convergent close-coupling (CCC) method was used within the non-relativistic LS-coupling framework to calculate the magnetic sublevel scattering amplitudes. From these amplitudes all the parameters and cross sections at 20 eV impact energy were extracted in the full angular range in 1° steps. The experimental and theoretical results were found to be in good agreement, indicating that the CCC method can be reliably applied to elastic scattering by 138Ba( ... 6s6p 1P1) atoms, and possibly to other heavy elements when spin-orbit coupling effects are negligible. Small but significant asymmetry was observed in the cross sections for scattering to the left and to the right. It was also found that elastic electron scattering by the initially isotropic atomic ensemble resulted in the creation of significant alignment. As a byproduct of the present studies, elastic scattering cross sections for metastable 138Ba atoms were also obtained

Surface textured polymer fibers for microfluidics

This article introduces surface textured polymer fibers as a new platform for the fabrication of affordable microfluidic devices. Fibers are produced tens of meters-long at a time and comprise 20 continuous and ordered channels (equilateral triangle grooves with side lengths as small as 30 micrometers) on their surfaces. Extreme anisotropic spreading behavior due to capillary action along the grooves of fibers is observed after surface modification with polydopamine (PDA). These flexible fibers can be fixed on any surface - independent of its material and shape - to form three-dimensional arrays, which spontaneously spread liquid on predefined paths without the need for external pumps or actuators. Surface textured fibers offer high-throughput fabrication of complex open microfluidic channel geometries, which is challenging to achieve using current photolithography-based techniques. Several microfluidic systems are designed and prepared on either planar or 3D surfaces to demonstrate outstanding capability of the fiber arrays in control of fluid flow in both vertical and lateral directions. Surface textured fibers are well suited to the fabrication of flexible, robust, lightweight, and affordable microfluidic devices, which expand the role of microfluidics in a scope of fields including drug discovery, medical diagnostics, and monitoring food and water quality. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Surface Textured Polymer Fibers for Microfluidics

Cataloged from PDF version of article.This article introduces surface textured polymer fibers as a new platform for the fabrication of affordable microfluidic devices. Fibers are produced tens of meters-long at a time and comprise 20 continuous and ordered channels (equilateral triangle grooves with side lengths as small as 30 micrometers) on their surfaces. Extreme anisotropic spreading behavior due to capillary action along the grooves of fibers is observed after surface modification with polydopamine (PDA). These flexible fibers can be fixed on any surface - independent of its material and shape - to form three-dimensional arrays, which spontaneously spread liquid on predefined paths without the need for external pumps or actuators. Surface textured fibers offer high-throughput fabrication of complex open microfluidic channel geometries, which is challenging to achieve using current photolithography-based techniques. Several microfluidic systems are designed and prepared on either planar or 3D surfaces to demonstrate outstanding capability of the fiber arrays in control of fluid flow in both vertical and lateral directions. Surface textured fibers are well suited to the fabrication of flexible, robust, lightweight, and affordable microfluidic devices, which expand the role of microfluidics in a scope of fields including drug discovery, medical diagnostics, and monitoring food and water quality. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim