Systems, methods, and apparatus for differential phase contrast microscopy by transobjective differential epi-detection of forward scattered light are provided. In some embodiments, a microscope objective comprises: a housing with mounting threads at a second end; optical components defining an optical axis, comprising: an objective lens mounted at a first end, configured to collect light from a sample placed in a field of view, the plurality of optical components create a pupil plane at a first distance along the optical axis at which rays having the same angle of incidence on the objective lens converge at the same radial distance from the optical axis; a photodetector within the housing offset from the optical axis at a second distance along the optical axis; and another photodetector within the housing at second distance along the optical axis and offset from the optical axis in the opposite direction from the first photodetector.

Holographic Video Microscopy analysis of non-spherical particles is disclosed herein. Properties of the particles are determined by application of light scattering theory to holography data. Effective sphere theory is applied to provide information regarding the reflective index of a sphere that includes a target particle. Known particles may be co-dispersed with unknown particles in a medium and the holographic video microscopy is used to determine properties, such as porosity, of the unknown particles.

For analyzing a sample containing particles of at least two categories, such as a sample containing blood cells, a particle counter subject to a detection limit is coupled with an analyzer capable of discerning particle number ratios, such as a visual analyzer, and a processor. A first category of particles can be present beyond detection range limits while a second category of particles is present within respective detection range limits. The concentration of the second category of particles is determined by the particle counter. A ratio of counts of the first category to the second category is determined on the analyzer. The concentration of particles in the first category is calculated on the processor based on the ratio and the count or concentration of particles in the second category.

Methods to detect contaminants in a solution and applications thereof are described. Generally, solutions are printed onto a substrate and then imaged via Raman spectroscopy, which can be utilized to detect signals derived from contaminants.

Biosensing platform for simultaneous, multiplexed, high throughput and ultra-sensitive optical detection of biomarkers labelled with plasmonic nanoparticles, the platform being provided with a biosensor, a broadband and continuous spectrum illumination source, an optical detector for simultaneously capturing spatially resolved and spectrally resolved the scattering signal of each individual nanoparticle, an autofocus system and an optical system adapted to collect the scattered signal of the biosensor's surface onto the optical detector, the platform being provided with translation means for the optical system and/or the biosensor, such that the optical system and the biosensor can be displaced relative to each other in the three dimensions, and wherein the processing means are adapted to: i) simultaneously capture spatially and spectrally resolved scattering signals from each nanoparticle individually, and ii) to analyze these signals simultaneously with the capture process.

Provided herein are embodiments of methods and systems for screening cellular, subcellular, and multicellular structures. In one embodiment, a method for screening is provided comprising the steps of introducing a plurality of cellular, subcellular, or multicellular structures, or a combination thereof, to an imaging system, wherein one or more structures of the plurality comprise one or more taggable markers; imaging the plurality of structures using the imaging system; identifying one or more target structures among the plurality of structures based on one or more properties of the target structures; tagging the target structures to produce tagged target structures, wherein each target structure is selectively illuminated by an excitation light, thereby causing one or more taggable markers within the target structure to be phototransformed to produce one or more phototransformed taggable markers within the target structure; and isolating one or more tagged target structures from the plurality of structures.

The present disclosure relates to a high throughput, scalable system for electroporation of biological cells. The two part system comprises an electroporation reaction array that interfaces with a control unit, providing electrical pulse, temperature control, and mixing of the sample contents. The control unit automates the entire process; electroporation, cell recovery and outgrowth are performed in a electroporation array assembly. The bottom of each reaction well of the electroporation array assembly contains a pair of coplanar electrodes. The bottom surface containing the electrodes is treated in a way to render it hydrophilic. This results in increased wetting of the electrodes thereby increasing transformation efficiency. The electrode configuration allows for processing of smaller sample volumes, reducing the consumption of expensive biological reagents by several orders of magnitude compared to conventional cuvette-based electroporation devices.

A microfluidic device comprises a cell flow layer and a control layer. The cell flow layer includes a growth channel, a collection channel, a plurality of bridge channels connecting the growth channel and the collection channel, a plurality of bridge valve portions, and a plurality of cell growth trenches coupled to the growth channel. The growth channel includes an inlet valve portion and an outlet valve portion controlling flow into and out of the growth channel. The collection channel includes an inlet valve portion and an outlet valve controlling flow into and out of the collection channel. The bridge valve portions control flow between the growth channel and the collection channel. The control layer includes a first control channel actuating the bridge valve portions and a second control channel actuating the inlet valve portions and the outlet valve portions of the growth channel and the collection channel.

Disclosed is a method for diagnosing a neurodegenerative disease in a subject. The method comprises obtaining from the subject a sample comprising at least one live blood cell, and optionally isolating at least one live blood cell from the sample. The method further comprises generating one or more multispectral or hyperspectral images of the at least one cell, and analysing spectral characteristics of autofluorescence from the at least one cell. Also disclosed is a system configured to aid in the detection or diagnosis of a neurodegenerative disease. Also disclosed is a method for selecting a subject for treatment for a neurodegenerative disease. Also disclosed is a method for monitoring the response of a subject to a therapeutic treatment for a neurodegenerative disease. Also disclosed is a protocol for monitoring the efficacy of a therapeutic treatment for a neurodegenerative disease.

A cell area extraction unit (241) extracts a cell area in a phase image that is created based on a hologram obtained by in-line holographic microscope (IHM). A background value acquisition unit (242) obtains a background value from phase values at a plurality of positions outside the cell area. An intracellular phase value acquisition unit (243) averages a plurality of phase values on a sampling line set at a position close to the periphery of a cell, while avoiding a central portion in which the phase value may be lowered in the cell area, to obtain an intracellular phase value. A phase change amount calculation unit (244) obtains the difference between the intracellular phase value and the background value. A phase change amount determination unit (245) compares the value of the difference with thresholds in two levels to determine whether the cell is in an undifferentiated state or an undifferentiation deviant state. It is thereby possible to automatically make a correct determination while removing the influence of a theoretical measurement error by IHM.