Abstract: An imaging substrate is provided to facilitate wide field photothermal infrared spectroscopic imaging of samples disposed thereon. The substrate includes at least two reflective layers and at least one spacer layer disposed therebetween which, together, form an optical cavity. The spacer layer(s) exhibit expansion and/or refractive index change as a function of heating by incident infrared illumination. Such localized heating results in a localized change in the effective reflectivity of the substrate by locally tuning/detuning the optical cavity. Thus, the pattern of effective reflectivity of the substrate can be made to correspond to the pattern of infrared absorptivity of a sample mounted on the substrate by illuminating the sample and the substrate with infrared illumination.

Abstract: A method for nanoscale tomographic infrared absorption imaging is provided, the method including: generating a first plurality of sets of probe measurements for a plurality of sample locations located across a surface of a sample, and measuring a magnitude and phase of a variation in displacement of the surface of the sample at the particular sample location at the second frequency, wherein the first frequency and the second frequency differ; and generating, based on the first plurality of sets of probe measurements, a three-dimensional tomographic map of absorption of infrared light at the first wavelength by the sample. Generating measurements for a particular location includes generating a first probe measurement by illuminating the sample with infrared light that varies at a first frequency and measuring a variation in displacement of the surface of the sample at the particular sample location at the first frequency.

Abstract: Methods and apparatus for obtaining a vibrational circular dichroism (VCD) image using a discrete frequency infrared (DFIR) microscope are disclosed. The method includes generating a pulsed laser beam comprising a spectral frequency, which may be tunable; modulating the laser beam to generate circularly polarized light; illuminating a sample and collecting, and detecting an optical signal transmitted or transflected from the location of the sample. The detected signal is demodulated at, for example, both the pulse frequency and the sum or difference of the pulse frequency and the modulating frequency to obtain an intensity value that correspond to the absorbance, and a polarization-dependent value that corresponds to the VCD. Other configurations of the apparatus may be employed to measure VCB and VLD.

Abstract: Methods and apparatus are provided for imaging a response of a sample to radiative heating. A method in accordance with one embodiment has steps of: illuminating a first area of the sample with a radiative heating beam; illuminating a portion of the first area with a probe beam; collecting light exiting the sample due to interaction of the probe beam with the sample; superimposing the light exiting the sample with a reference beam derived from the probe beam, wherein the reference is characterized by an optical phase relative to the probe beam; detecting a spatial portion of the light exiting the sample and the reference beam with at least one detector to generate an interference signal; and processing the interference signal to obtain an image of the sample associated with absorption of the radiative heating beam.

Abstract: A method for nanoscale tomographic infrared absorption imaging is provided, the method including: generating a first plurality of sets of probe measurements for a plurality of sample locations located across a surface of a sample, and measuring a magnitude and phase of a variation in displacement of the surface of the sample at the particular sample location at the second frequency, wherein the first frequency and the second frequency differ; and generating, based on the first plurality of sets of probe measurements, a three-dimensional tomographic map of absorption of infrared light at the first wavelength by the sample. Generating measurements for a particular location includes generating a first probe measurement by illuminating the sample with infrared light that varies at a first frequency and measuring a variation in displacement of the surface of the sample at the particular sample location at the first frequency.

Abstract: The disclosure is directed to methods and apparatus for obtaining a discrete frequency infrared (DFIR) spectroscopic image. The method includes generating, by a laser source, a pulsed laser beam comprising a spectral frequency in a mid-IR region and a pulse repetition rate; transmitting, by a first group of optical components, the pulsed laser beam onto a location of a sample; collecting, by a second group of optical components, an optical signal emitting from the location of the sample onto a detector to obtain a raw electric signal; demodulating, by a demodulator based on the pulse repetition rate, the raw electric signal to obtain an intensity value; and determining, by a control device and based on the intensity value, a pixel value corresponding to the spectral frequency in a DFIR spectroscopic image.

Abstract: A coated tubular construct for biological and industrial applications includes a plurality of channels, where each channel is radially surrounded by a wall comprising a first polymer, and a conformal coating comprising a second polymer is disposed on an outer and/or an inner surface of each wall. A method of producing a tubular construct includes 3D printing a template structure comprising a sacrificial material and a photoinitiator, and immersing the template structure in a first prepolymer solution comprising a first prepolymer and a co-initiator. During the immersion, the template structure is exposed to light, and the first prepolymer undergoes radical polymerization to conformally coat the template structure with the first polymer, forming a coated template. The sacrificial material is removed from the coated template, and a tubular construct comprising the first polymer is formed.

Abstract: Segmentation or other classification of digital pathology images with a deep learning model allows for sophisticated spatial features for cancer diagnosis to be extracted in an automated, fast, and accurate manner. A tiered analysis of tissue structure based in part on deep learning methods is provided. First, tissues depicted in a digital pathology image are segmented into cellular compartments (e.g., epithelial and stromal compartments). Second, the heterogeneity in the different cellular compartments are examined based on a clustering algorithm. Tissue can then be characterized in terms of inertia (or other spatial measures or features), which can be used to recognize disease. In some instances, multidimensional inertia (i.e., inertia computed in different cellular compartments or clustered components) can be used as an indicator of disease and its outcome.

Abstract: Methods and apparatus for obtaining a vibrational circular dichroism (VCD) image using a discrete frequency infrared (DFIR) microscope are disclosed. The method includes generating a pulsed laser beam comprising a spectral frequency, which may be tunable; modulating the laser beam to generate circularly polarized light; illuminating a sample and collecting, and detecting an optical signal transmitted or transflected from the location of the sample. The detected signal is demodulated at, for example, both the pulse frequency and the sum or difference of the pulse frequency and the modulating frequency to obtain an intensity value that correspond to the absorbance, and a polarization-dependent value that corresponds to the VCD. Other configurations of the apparatus may be employed to measure VCB and VLD.

Abstract: The disclosure is directed to a method and apparatus for correcting responsivity variation in photothermal imaging. The method includes sending, during a first time period, light-driving signal to a light source so that the light source is configured to output a series of light pulses onto a sample, wherein the sample is under photothermal-induced expansion according to the series of light pulses. The method includes obtaining, during the first time period, first deflection signal from a cantilever. The method includes sending, during a second time period, actuator-driving signal to an electromechanical actuator so that the electromechanical actuator is configured to move according to the actuator-driving signal, wherein the electromechanical actuator is coupled with the sample. The method includes obtaining, during the second time period, second deflection signal from the cantilever and obtaining a photothermal image of the sample based on the first deflection signal and the second deflection signal.

Abstract: The disclosure is directed to methods and apparatus for obtaining a discrete frequency infrared (DFIR) spectroscopic image. The method includes generating, by a laser source, a pulsed laser beam comprising a spectral frequency in a mid-IR region and a pulse repetition rate; transmitting, by a first group of optical components, the pulsed laser beam onto a location of a sample; collecting, by a second group of optical components, an optical signal emitting from the location of the sample onto a detector to obtain a raw electric signal; demodulating, by a demodulator based on the pulse repetition rate, the raw electric signal to obtain an intensity value; and determining, by a control device and based on the intensity value, a pixel value corresponding to the spectral frequency in a DFIR spectroscopic image.

Abstract: The disclosure is directed to a method and apparatus for correcting responsivity variation in photothermal imaging. The method includes sending, during a first time period, light-driving signal to a light source so that the light source is configured to output a series of light pulses onto a sample, wherein the sample is under photothermal-induced expansion according to the series of light pulses. The method includes obtaining, during the first time period, first deflection signal from a cantilever. The method includes sending, during a second time period, actuator-driving signal to an electromechanical actuator so that the electromechanical actuator is configured to move according to the actuator-driving signal, wherein the electromechanical actuator is coupled with the sample. The method includes obtaining, during the second time period, second deflection signal from the cantilever and obtaining a photothermal image of the sample based on the first deflection signal and the second deflection signal.

Abstract: Methods and apparatus are provided for imaging a response of a sample to radiative heating. A method in accordance with one embodiment has steps of: illuminating a first area of the sample with a radiative heating beam; illuminating a portion of the first area with a probe beam; collecting light exiting the sample due to interaction of the probe beam with the sample; superimposing the light exiting the sample with a reference beam derived from the probe beam, wherein the reference is characterized by an optical phase relative to the probe beam; detecting a spatial portion of the light exiting the sample and the reference beam with at least one detector to generate an interference signal; and processing the interference signal to obtain an image of the sample associated with absorption of the radiative heating beam.

Abstract: The present disclosure provides methods, systems, and computer-readable storage media that can be used to image an unstained sample. Traditionally histopathology and immunohistochemistry methods use stains or dyes in combination with microscopy (or other detection methods) to detect cells and cellular structures, such as proteins. However, the disclosed methods do not require the use of such stains and dyes. The disclosed methods can include obtaining a spectroscopic image (e.g., infrared (IR) imaging data) of the sample, analyzing the resulting spectroscopic image to reduce the dimensionality of the spectroscopic image, comparing the reduced spectroscopic image compared to a control (e.g., by using an appropriately trained algorithm) and generating an output computed stain image from the reduced IR spectra, thereby imaging the sample without the use of stains or dyes.

Abstract: The present disclosure provides methods, systems, and computer-readable storage media that can be used to image an unstained sample. Traditionally histopathology and immunohistochemistry methods use stains or dyes in combination with microscopy (or other detection methods) to detect cells and cellular structures, such as proteins. However, the disclosed methods do not require the use of such stains and dyes. The disclosed methods can include obtaining a spectroscopic image (e.g., infrared (IR) imaging data) of the sample, analyzing the resulting spectroscopic image to reduce the dimensionality of the spectroscopic image, comparing the reduced spectroscopic image compared to a control (e.g., by using an appropriately trained algorithm) and generating an output computed stain image from the reduced IR spectra, thereby imaging the sample without the use of stains or dyes.

Abstract: The present disclosure provides methods, systems, and computer-readable storage media that can be used to image an unstained sample. The disclosed methods can include obtaining a spectroscopic image (e.g., infrared (IR) imaging data) of the sample, analyzing the resulting spectroscopic image to reduce the dimensionality of the spectroscopic image, comparing the reduced spectroscopic image compared to a control (e.g., by using an appropriately trained algorithm) and generating an output computed stain image from the reduced IR spectra, thereby imaging the sample without the use of stains or dyes.

Abstract: This application provides to a method for identifying one or more prostate tissue samples in a database that are closest to a test prostate sample, which can be used to aid pathologists when examining prostate tissues to attain reliable and consistent diagnoses of prostate cancer. Also provided are databases and computer algorithms that can be used with such methods.

Abstract: This application provides to a method for identifying one or more prostate tissue samples in a database that are closest to a test prostate sample, which can be used to aid pathologists when examining prostate tissues to attain reliable and consistent diagnoses of prostate cancer. Also provided are databases and computer algorithms that can be used with such methods.

Abstract: The present disclosure relates to methods of diagnosing prostate cancer using different imaging methods. For example, it is shown herein that combining a Fourier transform infrared (FT-IR) spectroscopic image with an optical image (such as a hematoxylin and eosin image) allows for automated detection of prostate cancer with high accuracy.

Abstract: Embodiments of nanostructured, multilayered metal-dielectric particles suitable for use as Raman spectroscopic probes are disclosed, as well as methods of designing, making and using such multilayered nanoparticles, and kits including the multilayered nanoparticles. The multilayered nanoparticles include alternating metal and dielectric layers and an outer dielectric shell. One or more of the dielectric layers may include a plurality of reporter molecules. Embodiments of the multilayered nanoparticles are suitable for detecting target analytes in a sample. Some embodiments of the multilayered nanoparticles are suitable for use in multiplexed assays, including assays for multiple target analytes having differing concentrations.