Abstract: Genome whole chromosome analysis is a critical gold standard method for clinicians to study molecular lesions at single cell level in diseases and cancers. However, they suffer from low-sample-yielding, labor-intensive procedures that require subjective manual involvement of highly trained professionals. Here we disclose new devices, systems, and methods to automate, standardize, and accelerate the digital cytopathological sample and data generation with improved data quality to enable precision medicine and improve clinical practice. This disclosure describes a family of micro-fluidic devices, and accompanying methods for using said devices, to perform cytogenomic analysis on cells, nucleus, vesicles exosomes and their respective chromosomes, chromatins, nucleic acid polymers, subcellular genomic elements and any other dynamic transitional states between these forms.

Abstract: Disclosed are methods and devices for analyzing the 3D spatial and temporal nucleic acid secondary, tertiary and quaternary structures with a fluorescent interrogation system.

Abstract: A method of tracking proximity relationships is disclosed, comprising: (a) introducing a body into a solution of bio-molecule(s), said body comprising at least two capture probes, wherein each capture probe comprises a barcode and a capture domain, and at least one capture probe is a releasable capture probe, connected to the body via at least one cleavable linker; (b) allowing at least two capture probes to bind to their respective target bio-molecule(s) via their respective capture domains; and (c) releasing the at least one releasable capture probe from the body by cleaving its at least one cleavable linker.

Abstract: Genome whole chromosome analysis is a critical gold standard method for clinicians to study molecular lesions at single cell level in diseases and cancers. However, they suffer from low-sample-yielding, labor-intensive procedures that require subjective manual involvement of highly trained professionals. Here we disclose new devices, systems, and methods to automate, standardize, and accelerate the digital cytopathological sample and data generation with improved data quality to enable precision medicine and improve clinical practice. This disclosure describes a family of micro-fluidic devices, and accompanying methods for using said devices, to perform cytogenomic analysis on cells, nucleus, vesicles exosomes and their respective chromosomes, chromatins, nucleic acid polymers, subcellular genomic elements and any other dynamic transitional states between these forms.

Abstract: Disclosed herein are methods, compositions and systems for the interrogation of macromolecules, more particularly for preparation of isolated single macromolecules for subsequent processing of specific regions of interest within said macromolecule based on an analysis of the molecule's physical map. The disclosure is further related to the controlled segmentation of long nucleic acid parent molecules into smaller child molecules in a targeted manner such that further processing on said children may be performed with the knowledge of their origin within the parent, in a controlled environment enabled by purposefully designed microfluidic devices. Also disclosed is binding of regional specific barcodes along the length of a long nucleic acid molecule such that upon cleavage of said molecule into child molecules, the regional origin of the children can be tracked, in a controlled environment enabled by purposefully designed microfluidic devices.

Abstract: Disclosed are methods for generating physical maps from feature density profiles of a nucleic acid using a constriction device, and associated methods of analyzing said genomic profiles. In addition, disclosed are devices and methods for analyzing secondary, tertiary and quaternary structures on nucleic acids in spatial and temporal context of the 3-D organization of the genome in a constriction or sensor device.

Abstract: Disclosed are methods and devices for analyzing the 3D spatial and temporal nucleic acid secondary, tertiary and quaternary structures with a fluorescent interrogation system.