A method is disclosed for acquiring a single, in-focus two-dimensional projection image of a live, three-dimensional cell culture sample, with a fluorescence microscope. One or more long-exposure “Z-sweep” images are obtained, i.e. via a single or series of continuous acquisitions, while moving the Z-focal plane of a camera through the sample, to produce one or more two-dimensional images of fluorescence intensity integrated over the Z-dimension. The acquisition method is much faster than a Z-stack method, which enables higher throughput and reduces the risk of exposing the sample to too much fluorescent light. The long-exposure Z-sweep image(s) is then input into a neural network which has been trained to produce a high-quality (in-focus) two-dimensional projection image of the sample. With these high-quality projection images, biologically relevant analysis metrics can be obtained to describe the fluorescence signal using standard image analysis techniques, such as fluorescence object count and other fluorescence intensity metrics (e.g., mean intensity, texture, etc.).

A method is disclosed for acquiring a single, in-focus two-dimensional projection image of a live, three-dimensional cell culture sample, with a fluorescence microscope. One or more long-exposure “Z-sweep” images are obtained, i.e. via a single or series of continuous acquisitions, while moving the Z-focal plane of a camera through the sample, to produce one or more two-dimensional images of fluorescence intensity integrated over the Z-dimension. The acquisition method is much faster than a Z-stack method, which enables higher throughput and reduces the risk of exposing the sample to too much fluorescent light. The long-exposure Z-sweep image(s) is then input into a neural network which has been trained to produce a high-quality (in-focus) two-dimensional projection image of the sample. With these high-quality projection images, biologically relevant analysis metrics can be obtained to describe the fluorescence signal using standard image analysis techniques, such as fluorescence object count and other fluorescence intensity metrics (e.g., mean intensity, texture, etc.).

Disclosed are verification techniques that can be implemented by a device that conducts biological tests to verify that the specimen holding area carries a valid biological specimen. In certain embodiments, the testing device includes a receiving mechanism to receive a carrier, and the carrier includes a holding area that is to carry or to be exposed to a biological specimen. The device can also include a camera module arranged to capture imagery of the carrier, and a processor. In some examples, the processor can capture the imagery of the carrier and identify a visual cue on the carrier. Then, the processor can verify, based on a manner of how the visual cue is displayed in the captured imagery, whether the holding area carries a valid biological specimen.

Methods for enhancing a fluorescence intensity of a sample by adding an aromatic compound thereto. Workflows for a combined fluorescence-MALDI microscopy/imaging instrument also are disclosed comprising combining MALDI imaging and fluorescence imaging of the same sample in one sample preparation step. The presently disclosed workflow reduces the sampling time to one workday and minimizes sample degradation.

Methods for enhancing a fluorescence intensity of a sample by adding an aromatic compound thereto. Workflows for a combined fluorescence-MALDI microscopy/imaging instrument also are disclosed comprising combining MALDI imaging and fluorescence imaging of the same sample in one sample preparation step. The presently disclosed workflow reduces the sampling time to one workday and minimizes sample degradation.

This disclosure provides methods and devices for the label-free detection of target molecules of interest. The principles of the disclosure are particularly applicable to the detection of biological molecules (e.g., DNA, RNA, and protein) using standard SiO.sub.2-based microarray technology.

This disclosure provides methods and devices for the label-free detection of target molecules of interest. The principles of the disclosure are particularly applicable to the detection of biological molecules (e.g., DNA, RNA, and protein) using standard SiO.sub.2-based microarray technology.

Specimen delimiting element which, at least in one region, has a nano-porous material which is transparent to at least one observation radiation which is capturable by means of a microscope. The nano-porous material has pores, the mean pore diameter of which is smaller than the wavelength of the observation radiation, and a proportion of at least 5% of the volume of the nano-porous material is taken up by the pores at least in portions of said nano-porous material. The material has an open porosity, the mean pore diameter is at most 1000 nm, and the number of pores per unit volume of the nano-porous material and/or the mean pore diameter changes/change along at least one extent of the specimen delimiting element, such that a pore gradient is formed in the specimen delimiting element, and has at least one gradient portion in which no porosity is present, such that a separation of a specimen medium on one side surface of the specimen delimiting element and an immersion medium on an opposite side surface of the specimen delimiting element is effected by means of the specimen delimiting element. The invention furthermore relates to a microscopy method and to a microscope using the specimen delimiting element.

Specimen delimiting element which, at least in one region, has a nano-porous material which is transparent to at least one observation radiation which is capturable by means of a microscope. The nano-porous material has pores, the mean pore diameter of which is smaller than the wavelength of the observation radiation, and a proportion of at least 5% of the volume of the nano-porous material is taken up by the pores at least in portions of said nano-porous material. The material has an open porosity, the mean pore diameter is at most 1000 nm, and the number of pores per unit volume of the nano-porous material and/or the mean pore diameter changes/change along at least one extent of the specimen delimiting element, such that a pore gradient is formed in the specimen delimiting element, and has at least one gradient portion in which no porosity is present, such that a separation of a specimen medium on one side surface of the specimen delimiting element and an immersion medium on an opposite side surface of the specimen delimiting element is effected by means of the specimen delimiting element. The invention furthermore relates to a microscopy method and to a microscope using the specimen delimiting element.

An observation apparatus includes an acquisition unit that acquires positional information indicating a position of a bottom surface of a support for supporting an observation target, an imaging optical system that forms an optical image showing the observation target supported by the support on an image plane, a focus adjustment unit that adjusts a focal position of the imaging optical system based on the positional information acquired by the acquisition unit, and a control unit that performs control for matching an inclination of the image plane on which the optical image is formed to an inclination of an imaging surface of an imaging element based on the positional information acquired by the acquisition unit.