A method is provided comprising: positioning a slide that includes a concave region that is formed in a top surface of the slide and that can contain an object, such that a focal point of an objective lens of a fluorescence lifetime imaging microscopy (FLIM) device is within an area of the concave region between a bottom surface of the concave region and the top surface of the slide; and using the FLIM device to capture a sequence of wide field images of a portion of the object within a field of view of the objective lens.

Provided herein are systems and methods for simultaneous imaging and stimulation using a microscope system. The microscope system can have a relatively small size compared to an average microscope system. The microscope can comprise in part an imaging light source and a stimulation light source. Light from the imaging light source and the stimulation light source can be spectrally separated to reduce cross talk between the stimulation light and the imaging light.

This disclosure relates generally to detecting multiple biomarkers on or within a sample, though more specifically, to detecting individual detection moieties within a plurality of detection moieties.

An inspection apparatus is an inspection apparatus includes an excitation light source that generates excitation light to irradiate the object, a dichroic mirror that separates fluorescence from the sample by transmitting or reflecting the fluorescence according to a wavelength, a camera that images fluorescence reflected by the dichroic mirror, a camera that images fluorescence transmitted through the dichroic mirror, and a control apparatus that derives color irregularity information of a light-emitting element based on a first fluorescence image acquired by the camera and a second fluorescence image acquired by the camera, and an edge shift width corresponding to a width of a wavelength band in which transmittance and reflectance change according to a change in wavelength in the dichroic mirror is wider than a full width at half maximum of a normal fluorescence spectrum of the light-emitting element.

A quantum dot microscope apparatus is provided. A further aspect employs a tilted or tapered end or tip on a microscopic probe. Another aspect of the present apparatus employs a probe including a quantum dot with only one tunneling lead connected to a power source. A manufacturing aspect includes creating a tapered or asymmetrically shaped specimen-facing end of a probe where a quantum dot is located on the end. A further manufacturing aspect includes using focused ion-beam milling to create a tip or end of a quantum dot microscope probe.

Methods and systems for digitally reconstructing a patient tissue sample are described herein. In one embodiment, the method may include projecting a first structured light pattern onto the patient tissue sample, receiving a first reflection of the first structured light pattern from the patient tissue sample, and reconstructing the patient tissue sample based on the first reflection and the projected first structured light pattern. In another embodiment, the system may include a projector adapted or configured to project the first structured light onto the patient tissue sample, a charge-coupled device (CCD) adapted or configured to receive the first reflection from the patient tissue sample, and a reconstruction device adapted or configured to reconstruct the patient tissue sample based on the first reflection and the projected first structured light pattern.

The invention discloses a Trace Microanalysis Microscope System for high throughput screening. A multimodal imaging sensor arrangement acquires color, multispectral, hyperspectral and multi-directional polarized imaging, independently and in combinations thereof. In one aspect of this disclosure, the multimodal acquisition is combined with a plurality of sample illumination modes, further expanding the dimensionality of the generated data. In another aspect of this invention, machine learning-based methods combining and comparing a- priori data with the acquired multimodal data space, provide unique identifiers for the composition of the analyzed target objects. In yet another aspect of this invention, projection mapping of the identified compositional features navigates secondary sampling for subsequent analyses.

Laser emission based microscope devices and methods of using such devices for detecting laser emissions from a tissue sample are provided. The scanning microscope has first and second reflection surfaces and a scanning cavity holding a stationary tissue sample with at least one fluorophore/lasing energy responsive species. At least a portion of the scanning cavity corresponds to a high quality factor (Q) Fabry-Pérot resonator cavity. A lasing pump source directs energy at the scanning cavity while a detector receives and detects emissions generated by the fluorophore(s) or lasing energy responsive species. The second reflection surface and/or the lasing pump source are translatable with respect to the stationary tissue sample for generating a two-dimensional scan of the tissue sample. Methods for detecting multiplexed emissions or quantifying one or more biomarkers in a histological tissue sample, for example for detection and diagnosis of cancer, or other disorders/diseases are provided.

The present disclosure provides a method for detection of an analyte in a sample, where the sample is introduced into an analytic chamber along with droplets of an emulsion or gel beads. In another aspect, the present disclosure provides designs for formulations of emulsion drops or gel beads such that they are useful for detection of analytes in a massively parallel manner. Formulations that contain specific combinations of fluorescent particles allow optical determination of the identity of each fluorescent particle. The combinations are based on particle fluorescence emission wavelength, fluorescence excitation wavelength, and particle count.

A method (400) for microscopic examination of a sample (1) includes applying (410) the sample (1) to a sample holder (10) having a transparent carrier material, capturing (420) a first image (210, 220) of the sample (1) applied to the sample holder (10) using a first light-microscopy method, cryofixing, freeze-substituting, and subsequently infiltrating and embedding (430) the sample (1) together with the sample holder (10) with an embedding medium (20) in an embedding mold (90, 100), curing (440) the embedding medium (20), removing the sample (1) from the embedding mold (90, 100) together with the embedding medium (20) and the sample holder (10), capturing (450) a second image (230) of the sample (1) embedded in the cured embedding medium (20) using a second light-microscopy method, wherein at least partially identical regions of the sample (1) are captured in the first and second images, and identifying (460) at least one portion of the first image (210, 220) and one portion of the second image (230) which show identical regions of the sample (1).