Disclosed is an assay for determining resistance in a target cell or tissue to a therapy associated with cellular stress using chemical microscopy and high-throughput single cell analysis to determine functional metabolic alteration, including determining metabolic reprogramming in a target cell or tissue to a therapy associated with cellular stress, and methods of using the assays.

A system and method for determining the pH of tissue in vivo. A Raman spectrometer is used to collect Raman spectra from the target tissue. The Raman spectra are baseline subtracted and assessed to determine the concentration of HPO.sub.4.sup.−2 and H.sub.2PO.sub.4.sup.−1 for the purposes of calculating the pH. The approach was validate in vitro using PBS solutions of known pH. The approach was confirmed in vivo using rat and swine models by probing the immediate vicinity of a contusive spinal cord injury (SCI) in the first minutes and hours after injury. Using a dynamic analysis and the Henderson-Hasselbalch equation, the average of (N=12) noninvasive Raman-based pH measurements of CSF was 7.073±0.156 and at >95% confidence there is no statistically significant difference between the Raman-based and the physically sampled results.

Disclosed is an assay for determining resistance in a target cell or tissue to a therapy associated with cellular stress using chemical microscopy and high-throughput single cell analysis to determine functional metabolic alteration, including determining metabolic reprogramming in a target cell or tissue to a therapy associated with cellular stress, and methods of using the assays.

Systems and methods here may be used for automated capturing and analyzing spectrometer data of multiple sample gemstones on a stage, including mapping digital camera image data of samples, applying a Raman Probe to a first sample gemstone under evaluation on the stage, receiving spectrometer data of the sample gemstone from the probe, automatically moving the stage to a second sample, using the image data, and analyzing the other samples.

Systems and methods here may be used for automated capturing and analyzing spectrometer data of multiple sample gemstones on a stage, including mapping digital camera image data of samples, applying a Raman Probe to a first sample gemstone under evaluation on the stage, receiving spectrometer data of the sample gemstone from the probe, automatically moving the stage to a second sample, using the image data, and analyzing the other samples.

A system is provided. The system has a femtosecond oscillator to generate pulses used for pump and probe beams. A photonic crystal fiber is disposed in a path of the probe beam and produces pulses for a chirped probe beam. A high NA objective receives the pump and the chirped probe beam, redirects the received beams through a dielectric substrate towards an interface between a sample and the dielectric substrate to cause total internal reflection (TIR) at the sample-substrate interface, and produces corresponding evanescent waves in a portion of the sample adjacent to the sample-substrate interface, and collects a backward-propagating beam of pulses of responsive light. The portion of the sample illuminated by the evanescent waves emits responsive light. The dielectric substrate is transparent to the responsive light, the pump and the chirped probe beam. An image is produced having a specific image size using the received backward-propagating beam.

The invention is drawn to a photonic crystal fiber that can be used with nanoparticles to detect and quantify components in a test sample. The invention further relates to methods of using the photonic crystal fiber for detecting chemical and biological analytes, and in use in optical communications.

A substrate is provided with device structures and metrology structures (800). The device structures include materials exhibiting inelastic scattering of excitation radiation of one or more wavelengths. The device structures include structures small enough in one or more dimensions that the characteristics of the inelastic scattering are influenced significantly by quantum confinement. The metrology structures (800) include device-like structures (800b) similar in composition and dimensions to the device features, and calibration structures (800a). The calibration structures are similar to the device features in composition but different in at least one dimension. Using an inspection apparatus and method implementing Raman spectroscopy, the dimensions of the device-like structures can be measured by comparing spectral features of radiation scattered inelastically from the device-like structure and the calibration structure.

An exemplary laser microscope can be provided, comprising at least one first laser source which emits at least one (e.g., pulsed) excitation beam, a scanning optical configuration (e.g., configured to scan the excitation beam over the surface of a sample), a focusing optical configuration (e.g., configured to focus the excitation beam onto the sample), and at least one detector configured to detect light emitted by the sample due to an optical effect in response to the excitation beam. A second laser source facilitates a pulsed ablation beam for a local ablation of the material of the sample. The ablation beam can be guided to the sample via the scanning and focusing optical configurations. The first and second laser sources can be fed by a mutual continuous wave pump laser and/or a mutual pulsed pump laser. The first laser source can emit pulses with at least two different wavelengths.

The present disclosure relates to a surface-enhanced Raman spectroscopy complex probe capable of effectively detecting a catecholamine compound even at extremely low concentrations. The complex probe includes a nanolaminate including a nanogap and metal nanoparticles. In this case, the nanolaminate and the metal nanoparticles are modified to a compound that may be bound to each functional group included in catecholamine, and thus, catecholamine included in an analyte is doubly recognized by the complex probe. In addition, since a hotspot emitting a strong SERS signal is formed by a nanogap included in a nanolaminate, it is possible to effectively detect a catecholamine compound even at extremely low concentrations.