The General Hospital Corporation

Shannon Stott

Mehmet Toner

Shannon Tessier

Eduardo Reategui

Ravi Kapur

Thomas Alan Barber

Chia-Hsien S Hsu

Ajay Shah

Lindong Weng

Rebecca Sandlin

Keith Wong

John Walsh

Mustafa Korkut Uygun

Eugene J Lim

Casie A Pendexter

Stephanie E J Cronin

Xiaocheng Jiang

Reinier Johan De Vries

This disclosure is related to methods of preserving biological samples, organs, and organisms. This disclosure is based, at least in part, on the discovery that in the presence of heterogenous extracellular ice, endothelial cells have improved attachment and viability after preservation, and particularly by uniformly nucleating ice across the microvasculature using ice nucleating agents, the chance of intracelluar ice formation can be significantly reduced.

High subzero cryopreservation

Systems, methods, and devices for selective capture and release of target particles, e.g., living cells, from liquid samples, e.g., blood, are provided. The particle capture systems include a substrate; a first layer of gelatin bound to the substrate by physical adsorption, wherein the gelatin is functionalized with a plurality of first members of a binding pair; a second layer of gelatin wherein the gelatin is functionalized with a plurality of the first members of the binding pair and the second layer is bound to the first layer via a plurality of second members of the binding pair that are associated with the first members of the binding pair on both the first and the second layers; and a plurality of nanostructures bound to the second members of the binding pair and to one or more particle-binding moieties that selectively bind to the target particles.

Capture and release of particles from liquid samples

Methods for stabilizing blood samples, e.g., clinical blood samples, for storage or transportation before use.

Stabilization of whole blood samples

Systems and techniques are described for capturing target extracellular vesicles from a fluid sample. In some implementations, a microfluidic device includes a microfluidic channel where an internal surface of at least one wall of the microfluidic channel includes a plurality of grooves or ridges, or both grooves and ridges, arranged and configured to generate chaotic mixing within a fluid sample flowing through the microfluidic channel. The microfluidic device also includes a plurality of elongate flexible linker molecules, each having a molecular weight between about 1.8-4.8 kDa, where each elongate flexible linker molecule is bound at a first end to an internal surface of at least one wall of the microfluidic channel and is bound at a second end to one or more binding moieties that specifically bind to a target extracellular vesicle.

Engineered nano-interfaces for microfluidic isolation of extracellular vesicles

This disclosure relates to ice nucleation formulations for cryopreservation and stabilization of biologics, and methods of use thereof.

Ice nucleation formulations for cryopreservation and stabilization of biologics

Methods for stabilizing blood samples, e.g., clinical blood samples, for storage or transportation before use. Exemplary applications include but are not limited to enrichment of leukocyte subtypes such as T-cells or neutrophils for cytokine and immuno-assays; isolation of progenitor cells from cord blood or peripheral blood for transplantation; isolation of fetal cells from the maternal blood for diagnosis; and sorting of circulating tumor cells for cancer detection and therapy.

Methods and systems for isolating platelet-associated nucleated target cells, e.g., such as circulating epithelial cells, circulating tumor cells (CTCs), circulating endothelial cells (CECs), circulating stem cells (CSCs), neutrophils, and macrophages, from sample fluids, e.g., biological fluids, such as blood, bone marrow, plural effusions, and ascites fluid, are described. The methods include obtaining a cell capture chamber including a plurality of binding moieties bound to one or more walls of the chamber, wherein the binding moieties specifically bind to platelets; flowing the sample fluid through the cell capture chamber under conditions that allow the binding moieties to bind to any platelet-associated nucleated target cells in the sample to form complexes; and separating and collecting platelet-associated nucleated target cells from the complexes.

Platelet-targeted microfluidic isolation of cells

Methods and systems capturing particles suspended in a fluid flowed through a micro-channel, can include flowing the fluid including the particles to be captured through a micro-channel and past a groove defined in a surface of a wall of the micro-channel such that flowing the fluid past the groove forms microvortices in the fluid; contacting at least some of the particles against an adherent disposed on one or more of walls of the microchannel after the microvortices form in the fluid; and capturing at least some of the particles contacting the adherent.

Capturing particles

Methods and systems for selectively capturing analytes, such as cells, e.g., circulating tumor cells (CTCs), from fluid samples are disclosed. The methods include contacting the sample with an analyte binding moiety that selectively binds to the analytes; optionally separating first components of the sample including a majority of the analytes bound to the binding moieties from second components of the sample using size-based separation, e.g., in a microfluidic channel; adding to the first components of the sample a plurality of binding agents under conditions that enable a plurality of the binding agents to be linked to the analyte binding moieties to form multivalent tagging agents bound to the analyte; passing the first components of the sample past a surface to which is attached a plurality of capture agents that selectively bind to the binding agents; and capturing the analytes by providing conditions that enable the multivalent tagging agents bound to the analytes to bind to one or more of the capture agents.

Growing community of inventors

Stoneham, MA, United States of America

Shannon Stott