Abstract: Raman spectra of cells, such as normal human T- and B-cells from peripheral blood or human tonsil and the corresponding transformed cells are obtained by optically trapping the cells and obtaining their Raman spectra. The trapped cells can be subjected to one, two, or more different excitation wavelengths, and each wavelength of the corresponding Raman spectra can be stored in a separate channel. In preferred embodiments, two spectra are subtracted from each other to give a difference spectrum and each channel is analyzed independently to characterize the trapped cell. Alternatively, the Raman spectrum can be subjected to Principal Component Analysis (PCA) in order to characterize the trapped cell. The trapped cell thus classified can be sorted, or further manipulated.

Abstract: A device and array coupled to capture molecules are provided. Specifically, the device and array can be used for detecting the presence and concentration of biomarkers in a sample from a subject. The device and array can also allow the use of a method for scoring a sample for, e.g., the purpose of diagnosing a disease. The method can also be advantageous to applications where there is a need to accurately determine the disease stage of a subject for the purpose of making therapeutic decisions.

Abstract: A device and array coupled to capture molecules are provided. Specifically, the device and array can be used for detecting the presence and concentration of biomarkers in a sample from a subject. The device and array can also allow the use of a method for scoring a sample for, e.g., the purpose of diagnosing a disease. The method can also be advantageous to applications where there is a need to accurately determine the disease stage of a subject for the purpose of making therapeutic decisions.

Abstract: A hand-held portable microarray reader for biodetection includes a microarray reader engineered to be small enough for portable applications. The invention includes a high-powered light-emitting diode that emits excitation light, an excitation filter positioned to receive the excitation light, a slide, a slide holder assembly for positioning the slide to receive the excitation light from the excitation filter, an emission filter positioned to receive the excitation light from the slide, a lens positioned to receive the excitation light from the emission filter, and a CCD camera positioned to receive the excitation light from the lens.

Abstract: A hand-held portable microarray reader for biodetection includes a microarray reader engineered to be small enough for portable applications. The invention includes a high-powered light-emitting diode that emits excitation light, an excitation filter positioned to receive the excitation light, a slide, a slide holder assembly for positioning the slide to receive the excitation light from the excitation filter, an emission filter positioned to receive the excitation light from the slide, a lens positioned to receive the excitation light from the emission filter, and a CCD camera positioned to receive the excitation light from the lens.

Abstract: Raman spectra of cells, such as normal human T- and B-cells from peripheral blood or human tonsil and the corresponding transformed cells are obtained by optically trapping the cells and obtaining their Raman spectra. The trapped cells can be subjected to one, two, or more different excitation wavelengths, and each wavelength of the corresponding Raman spectra can be stored in a separate channel. In preferred embodiments, two spectra are subtracted from each other to give a difference spectrum and each channel is analyzed independently to characterize the trapped cell. Alternatively, the Raman spectrum can be subjected to Principal Component Analysis (PCA) in order to characterize the trapped cell. The trapped cell thus classified can be sorted, or further manipulated.

Abstract: An aptamer based-sensor comprising: a target binding aptamer attaching a Raman probe and a metal coated surface; and related methods and systems

Abstract: A surface-enhanced Raman scattering method and apparatus to sequence polymeric biomolecules such as DNA, RNA, or proteins is introduced. The method uses metallic nanostructures such as, for example, spherical or cylindrical Au or Ag nanoparticles having characteristic lengths of 10-100 nm which when illuminated with light of the appropriate wavelength produce resonant oscillations of the conduction electrons (plasmon resonance). Electric field enhancements of 30-1000 near the particle surface resulting from such oscillations increase Raman scattering cross-sections by about 106-1015 due to the E4 dependence of the Raman scattering, wherein the largest enhancements occur in the gap/junction between novel closely spaced structures as disclosed herein.

Abstract: A device and array coupled to capture molecules are provided. Specifically, the device and array can be used for detecting the presence and concentration of biomarkers in a sample from a subject. The device and array can also allow the use of a method for scoring a sample for, e.g., the purpose of diagnosing a disease. The method can also be advantageous to applications where there is a need to accurately determine the disease stage of a subject for the purpose of making therapeutic decisions.

Abstract: Surface-Enhanced Raman Spectroscopy (SERS) is a vibrational spectroscopic technique that utilizes metal surfaces to provide enhanced signals of several orders of magnitude. When molecules of interest are attached to designed metal nanoparticles, a SERS signal is attainable with single molecule detection limits. This provides an ultrasensitive means of detecting the presence of molecules. By using selective chemistries, metal nanoparticles can be functionalized to provide a unique signal upon analyte binding. Moreover, by using measurement techniques, such as, ratiometric received SERS spectra, such metal nanoparticles can be used to monitor dynamic processes in addition to static binding events. Accordingly, such nanoparticles can be used as nanosensors for a wide range of chemicals in fluid, gaseous and solid form, environmental sensors for pH, ion concentration, temperature, etc., and biological sensors for proteins, DNA, RNA, etc.

Abstract: A microfluidic device made from nanolaminate materials that are capable of electrophoretic selection of particles on the basis of their mobility. Nanolaminate materials are generally alternating layers of two materials (one conducting, one insulating) that are made by sputter coating a flat substrate with a large number of layers. Specific subsets of the conducting layers are coupled together to form a single, extended electrode, interleaved with other similar electrodes. Thereby, the subsets of conducting layers may be dynamically charged to create time-dependent potential fields that can trap or transport charge colloidal particles. The addition of time-dependence is applicable to all geometries of nanolaminate electrophoretic and electrochemical designs from sinusoidal to nearly step-like.

Abstract: A method and apparatus with the sensitivity to detect and identify single target molecules through the localization of dual, fluorescently labeled probe molecules. This can be accomplished through specific attachment of the taget to a surface or in a two-dimensional (2D) flowing fluid sheet having approximate dimensions of 0.5 ?m×100 ?m×100 ?m. A device using these methods would have 103–104 greater throughput than previous one-dimensional (1D) micro-stream devices having 1 ?m3 interrogation volumes and would for the first time allow immuno- and DNA assays at ultra-low (femtomolar) concentrations to be performed in short time periods (˜10 minutes). The use of novel labels (such as metal or semiconductor nanoparticles) may be incorporated to further extend the sensitivity possibly into the attomolar range.

Abstract: Nanochannel electrophoretic and electrochemical devices having selectively-etched nanolaminates located in the fluid transport channel. The normally flat surfaces of the nanolaminate having exposed conductive (metal) stripes are selectively-etched to form trenches and baffles. The modifications of the prior utilized flat exposed surfaces increase the amount of exposed metal to facilitate electrochemical redox reaction or control the exposure of the metal surfaces to analytes of large size. These etched areas variously increase the sensitivity of electrochemical detection devices to low concentrations of analyte, improve the plug flow characteristic of the channel, and allow additional discrimination of the colloidal particles during cyclic voltammetry.

Abstract: Nanochannel electrophoretic and electrochemical devices having selectively-etched nanolaminates located in the fluid transport channel. The normally flat surfaces of the nanolaminate having exposed conductive (metal) stripes are selectively-etched to form trenches and baffles. The modifications of the prior utilized flat exposed surfaces increase the amount of exposed metal to facilitate electrochemical redox reaction or control the exposure of the metal surfaces to analytes of large size. These etched areas variously increase the sensitivity of electrochemical detection devices to low concentrations of analyte, improve the plug flow characteristic of the channel, and allow additional discrimination of the colloidal particles during cyclic voltammetry.

Abstract: Fluorescent biosensor molecules, fluorescent biosensors and systems, as well as methods of making and using these biosensor molecules and systems are described. Embodiments of these biosensor molecules exhibit fluorescence emission at wavelengths greater than about 650 nm. Typical biosensor molecules include a fluorophore that includes an iminium ion, a linker moiety that includes a group that is an anilinic type of relationship to the fluorophore and a boronate substrate recognition/binding moiety, which binds glucose. The fluorescence molecules modulated by the presence or absence of polyhydroxylated analytes such as glucose. This property of these molecules of the invention, as well as their ability to emit fluorescent light at greater than about 650 nm, renders these biosensor molecules particularly well-suited for detecting and measuring in-vivo glucose concentrations.

Abstract: Methods are provided for the determination of the concentration of biological levels of polyhydroxylated compounds, particularly glucose. The methods utilize an amplification system that is an analyte transducer immobilized in a polymeric matrix, where the system is implantable and biocompatible. Upon interrogation by an optical system, the amplification system produces a signal capable of detection external to the skin of the patient. Quantitation of the analyte of interest is achieved by measurement of the emitted signal.

Abstract: Nanolaminate materials are composites that consist of alternating layers of different materials (often conducting and insulating materials) that are manufactured by repeated sputter coating of a flat substrate. The layers can be exceedingly thin—on the order of a few atomic layers up to hundreds of nanometers. When the composite is cut perpendicular to the planes of these layers, a surface results that along one dimension has closely spaced alternating stripes of the materials. This patterned surface is incorporated into electrochemical and electrophoretic devices. The device may be positioned such that sample fluid may pass horizontally or vertically relative to the exposed closely spaced stripes. Such a device may be constructed to use an array of discrete conducting layers to define a voltage gradient so as to perform electrophoretic transport in a narrow fluid channel with one surface defined by the nanolaminate material.

Abstract: Electrophoric/electrochemical devices involving two separate, parallel, flat surfaces consisting of metal/insulator nano-laminates. The use of two nano-laminates increases the electrophoretic flow through a channel of given dimensions at a given applied voltage as compared to prior approaches. The introduction of these separate electrodes to the walls of the fluid channel maximizes the amount of exposed metal and minimizes the diffusion distance to facilitate electrochemical redox reactions. The combination of rapid solvent turnover and efficient detection of low concentrations of analyte creates a fast and sensitive detector.

Abstract: Nanochannel electrophoretic and electrochemical devices having selectively-etched nanolaminates located in the fluid transport channel. The normally flat surfaces of the nanolaminate having exposed conductive (metal) stripes are selectively-etched to form trenches and baffles. The modifications of the prior utilized flat exposed surfaces increase the amount of exposed metal to facilitate electrochemical redox reaction or control the exposure of the metal surfaces to analytes of large size. These etched areas variously increase the sensitivity of electrochemical detection devices to low concentrations of analyte, improve the plug flow characteristic of the channel, and allow additional discrimination of the colloidal particles during cyclic voltammetry.

Abstract: A microfluidic device made from nanolaminate materials that are capable of electrophoretic selection of particles on the basis of their mobility. Nanolaminate materials are generally alternating layers of two materials (one conducting, one insulating) that are made by sputter coating a flat substrate with a large number of layers. Specific subsets of the conducting layers are coupled together to form a single, extended electrode, interleaved with other similar electrodes. Thereby, the subsets of conducting layers may be dynamically charged to create time-dependent potential fields that can trap or transport charge colloidal particles. The addition of time-dependence is applicable to all geometries of nanolaminate electrophoretic and electrochemical designs from sinusoidal to nearly step-like.