Abstract: Systems and methods for sensing vibrational absorption induced photothermal effect via a visible light source. A Mid-infrared photothermal probe (MI-PTP, or MIP) approach achieves 10 mM detection sensitivity and sub-micron lateral spatial resolution. Such performance exceeds the diffraction limit of infrared microscopy and allows label-free three-dimensional chemical imaging of live cells and organisms. Distributions of endogenous lipid and exogenous drug inside single cells can be visualized. MIP imaging technology may enable applications from monitoring metabolic activities to high-resolution mapping of drug molecules in living systems, which are beyond the reach of current infrared microscopy.

Abstract: An example microscope includes a pump laser for providing a first illumination to a sample. A laser array provides a second illumination to the sample. The laser array may include a plurality of laser elements, each providing oblique illuminations to the sample. An illumination collecting source collects the first illumination and the second illumination from the sample. The illumination collecting source may capture transient 3D refractive index (RI) variations in the sample due to the first illumination and second illumination.

Abstract: A mid-infrared photothermal microscopy system images a sample. A mid-infrared optical source generates a mid-infrared beam which is directed along a first optical path to reach the substrate on a first side and heat the sample. A probe light source generates a probe light which is directed along a second optical path to reach the substrate on a second side and illuminate the sample. A first laser scanner is positioned along the first optical path and configured to rotate to redirect light and scan the sample with the mid-infrared beam. A second laser scanner is positioned along the second optical path and configured to rotate to redirect light and scan the sample with the probe light. The laser scanners each include at least one mirror driven to rotate such that the mid-infrared beam and the probe light scan the sample synchronously.

Abstract: Systems and methods implement of high-speed delay scanning for spectroscopic SRS imaging characterized by scanning a first pulsed beam across a stepwise reflective surface (such as a stepwise mirror or a reflective blazed grating) in a Littrow configuration to generate near continuous temporal delays relative to a second pulsed beam. Systems and methods also implement deep learning techniques for image restoration of spectroscopic SRS images using a trained encoder-decoder convolution neural network (CNN) which in some embodiments may be designed as a spatial-spectral residual net (SS-ResNet) characterized by two parallel filters including a first convolution filter on the spatial domain and a second convolution filter on the spectral domain.

Abstract: An example photoacoustic system for neurostimulation includes a light producing device for producing light of a specific wavelength. At least one nanotransducer is binded on a surface of a neuron. The nanotransducer converts the light with the specific wavelength into at least one acoustic wave at or near the neuron.

Abstract: An example microscope includes a pump laser for providing a first illumination to a sample. A laser array provides a second illumination to the sample. The laser array may include a plurality of laser elements, each providing oblique illuminations to the sample. An illumination collecting source collects the first illumination and the second illumination from the sample. The illumination collecting source may capture transient 3D refractive index (RI) variations in the sample due to the first illumination and second illumination.

Abstract: Systems and methods for detecting photothermal effect in a sample are described herein. In these systems and methods, a pump source is configured to generate a pump pulse train, a probe source is configured to generate a probe pulse train and is synchronized with the pump pulse train, and a camera collects the resulting data. The camera is configured to collect a first signal corresponding to a hot frame, wherein the hot frame includes visible probe beam as modified by a pump beam and a second signal corresponding to a cold frame, wherein the cold frame includes visible probe beam that has not been modified by a pump beam. A processor can subtract the second signal from the first signal to detect the photothermal effect.

Abstract: Microscopic analysis of a sample includes a system using dark-field illumination. A mid-IR optical source generates a mid-infrared beam, which is directed onto the sample to induce a temperature change by absorption of the mid-infrared beam. A visible light source generates a light illuminating the sample on a substrate and creating a scattered field and a reflected field along a collection path of the system. A pupil mask is positioned along the collection path to block the reflected field while allowing the scattered field to pass therethrough. A camera is positioned at an end of the collection path to collect the scattered field and generate a dark-field image of the sample.

Abstract: 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.

Abstract: Systems and methods implement of high-speed delay scanning for spectroscopic SRS imaging characterized by scanning a first pulsed beam across a stepwise reflective surface (such as a stepwise mirror or a reflective blazed grating) in a Littrow configuration to generate near continuous temporal delays relative to a second pulsed beam. Systems and methods also implement deep learning techniques for image restoration of spectroscopic SRS images using a trained encoder-decoder convolution neural network (CNN) which in some embodiments may be designed as a spatial-spectral residual net (SS-ResNet) characterized by two parallel filters including a first convolution filter on the spatial domain and a second convolution filter on the spectral domain.

Abstract: Systems and methods are provided for performing photothermal dynamic imaging. An exemplary method includes: scanning a sample to produce a plurality of raw photothermal dynamic signals; receiving the raw photothermal dynamic signals of the sample; generating a plurality of second signals by matched filtering the raw photothermal dynamic signals to reject non-modulated noise; and performing an inverse operation on the second signals to retrieve at least one thermodynamic signal in a temporal domain.

Abstract: A tapered fiber optoacoustic emitter includes a nanosecond laser configured to emit laser pulses and an optic fiber. The optic fiber includes a tip configured to guide the laser pulses. The tip has a coating including a diffusion layer and a thermal expansion layer, wherein the diffusion layer includes epoxy and zinc oxide nanoparticles configured to diffuse the light while restricting localized heating. The thermal expansion layer includes carbon nanotubes (CNTs) and Polydimethylsiloxane (PDMS) configured to convert the laser pulses to generate ultrasound. The frequency of the ultrasound is tuned with a thickness of the diffusion layer and a CNT concentration of the expansion layer.

Abstract: Methods of the present invention comprise photoinactivation of catalase in combination with low-concentration peroxide solutions and/or ROS generating agents to provide antibacterial effects.

Abstract: An example photoacoustic system for neurostimulation includes a light producing device for producing light of a specific wavelength. At least one nanotransducer is binded on a surface of a neuron. The nanotransducer converts the light with the specific wavelength into at least one acoustic wave at or near the neuron.

Abstract: Systems and methods are provided for performing photothermal dynamic imaging. An exemplary method includes: scanning a sample to produce a plurality of raw photothermal dynamic signals; receiving the raw photothermal dynamic signals of the sample; generating a plurality of second signals by matched filtering the raw photothermal dynamic signals to reject non-modulated noise; and performing an inverse operation on the second signals to retrieve at least one thermodynamic signal in a temporal domain.

Abstract: Microscopic analysis of a sample includes a system using dark-field illumination. A mid-IR optical source generates a mid-infrared beam, which is directed onto the sample to induce a temperature change by absorption of the mid-infrared beam. A visible light source generates a light illuminating the sample on a substrate and creating a scattered field and a reflected field along a collection path of the system. A pupil mask is positioned along the collection path to block the reflected field while allowing the scattered field to pass therethrough. A camera is positioned at an end of the collection path to collect the scattered field and generate a dark-field image of the sample.

Abstract: 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.

Abstract: A tapered fiber optoacoustic emitter includes a nanosecond laser configured to emit laser pulses and an optic fiber. The optic fiber includes a tip configured to guide the laser pulses. The tip has a coating including a diffusion layer and a thermal expansion layer, wherein the diffusion layer includes epoxy and zinc oxide nanoparticles configured to diffuse the light while restricting localized heating. The thermal expansion layer includes carbon nanotubes (CNTs) and Polydimethylsiloxane (PDMS) configured to convert the laser pulses to generate ultrasound. The frequency of the ultrasound is tuned with a thickness of the diffusion layer and a CNT concentration of the expansion layer.

Abstract: Systems and methods for sensing vibrational absorption induced photothermal effect via a visible light source. A Mid-infrared photothermal probe (MI-PTP, or MIP) approach achieves 10 mM detection sensitivity and sub-micron lateral spatial resolution. Such performance exceeds the diffraction limit of infrared microscopy and allows label-free three-dimensional chemical imaging of live cells and organisms. Distributions of endogenous lipid and exogenous drug inside single cells can be visualized. MIP imaging technology may enable applications from monitoring metabolic activities to high-resolution mapping of drug molecules in living systems, which are beyond the reach of current infrared microscopy.

Abstract: A method for the determination of antibiotic susceptibility through stimulated Raman scattering microscopy is disclosed. The method utilizes a imaging apparatus adapted to collect a laser signal through a sample having a bacteria for imaging the metabolism of the sample. The sample can be manipulated with an antibiotic for imaging to determine the susceptibility of a bacteria to the provided antibiotic.