Apparatus and methods are described use with a bodily sample that contains cells. A microscope (24) is focused, such that a focal plane of the microscope (24) at least approximately coincides with a level at which at least some cells belonging to the sample are at least partially disposed. At least one on-focus microscopic image of the sample, while the focal plane of the microscope (24) approximately coincides with the level. The microscope (24) is focused such that the focal plane of the microscope is offset with respect to the level, at least one off-focus microscopic image of the sample is acquired, while the focal plane of the microscope (24) is offset with respect to the level. A property of at least a portion of the sample is determined, at least partially based upon the on-focus and off-focus images. Other applications are also described.

Methods and apparatuses relating to measuring sample parameters and cell parameters (e.g., cell size, cell shape) are provided herein. The present disclosure provides additional methods, systems and techniques for improving osmotic gradient generating systems for vise in technologies to accurately determine red blood cell volume and the osmolality at which cells achieve a maximum volume.

A system or method for detecting an immune system activation state in a patient can include a sample preparation system configured to isolate white blood cells from a sample of the patient, a cytometry module configured to determine biophysical properties of the white blood cells of the sample, and an analysis module configured to analyze the biophysical properties.

Light detection systems are provided. Aspects of the light detection systems include first and second light receivers in fixed positions relative to each other, a plurality of wavelength separators configured to pass light from the first and second light receivers having a predetermined spectral range, and a plurality of light detection modules. Baseplates having a stage for mounting a light receiver, a plurality of recesses for fixing a plurality of light detection modules in rigid alignment relative to the stage, and a heat dissipation opening positioned within each recess are also provided. In addition, particle analysis systems, methods and kits for practicing the invention are disclosed.

Described herein are apparatuses for analyzing an optical signal decay. In some embodiments, an apparatus includes: a source of a beam of pulsed optical energy; a sample holder configured to expose a sample to the beam; a detector comprising a number of spectral detection channels configured to convert the optical signals into respective electrical signals; and a signal processing module configured to perform a method. In some embodiments, the method includes: receiving the electrical signals from the detector; mathematically combining individual decay curves in the electrical signals into a decay supercurve, the supercurve comprising a number of components, each component having a time constant and a relative contribution to the supercurve; and numerically fitting a model to the supercurve.

A method and/or system can include processing a blood sample of a patient by degrading red blood cells of the blood sample using a lysing solution, quenching the degradation of the red blood cells after a threshold lysing time, centrifuging and aspirating the quenched solution to remove degraded red blood cell debris and concentrate white blood cells of the blood sample, and suspending the concentrated white blood cells in a buffer solution; within a threshold transfer time, deforming white blood cells, of the suspended white blood cells, within a microfluidic chip; and determining a probability that the patient is in an immune activation state based on images of the white blood cells acquired while deforming the white blood cells.

This disclosure describes single-use test cartridges, cell analyzer apparatus, and methods for automatically performing microscopic cell analysis tasks, such as counting and analyzing blood cells in biological samples. A small measured quantity of a biological sample, such as whole blood, is placed in a mixing bowl on the disposable test cartridge after being inserted into the cell analyzer. The analayzer also deposits a known amount of diluent/stain in the mixing bowl and mixes it with the blood. The analyzer takes a measured amount of the mixture and dispenses in a sample cup on the cartridge in fluid communication with an imaging chamber. The geometry of the imaging chamber is chosen to maintain the uniformity of the mixture, and to prevent cells from crowding or clumping as it is transferred into the imaging chamber by the analyzer. Images of all of the cellular components within the imaging chamber are counted and analyzed to obtain a complete blood count.

Systems and methods analyzing body fluids contain cells including blood, bone marrow, urine, vaginal tissue, epithelial tissue, tumors, semen, and spittle are disclosed. The systems and methods utilize an improved technique for applying a monolayer of cells to a slide and generating a substantially uniform distribution of cells on the slide. Additionally aspects of the invention also relate to systems and method for utilizing multi-color microscopy for improving the quality of images captured by a light receiving device.

A polypeptide encoding a chimeric antigen receptor (CAR) comprising at least one extracellular binding domain that comprises a scFv formed by at least a VH chain and a VL chain specific to an antigen, wherein said extracellular binding domain comprises at least one mAb-specific epitope.

A fractionated photoacoustic flow cytometry (PAFC) system and methods for the in vivo detection of target objects in biofluidic systems (e.g., blood, lymph, urine, or cerebrospinal fluid) of a living organism is described. The fractionated system includes a fractionated laser system, a fractionated optical system, a fractionated acoustic system, and combinations thereof. The fractionated laser system includes at least one laser or laser array for pulsing a target object within the circulatory vessel with fractionated focused laser beams. The fractionated optical system separates one or several laser beams into multiple beams in a spatial configuration on the skin above the circulatory vessel of the living organism. The fractionated acoustic system includes multiple focused ultrasound transducers for receiving photoacoustic signals emitted by the target object in response to the fractionated laser beams. The target objects have intrinsic photoacoustic contrast or may be labeled with photoswitchable or spaser-based probes. Fractioned beams may be used also for diagnostics with other spectroscopic methods (e.g., fluorescence, Raman or scattering) and energy sources both coherent and conventional such as lamp and LED in the broad spectral range from 10 Å to 1 cm (e.g., X-ray, UV, visible, NIR or microwaves) in continuous wave and pulse modes.