Abstract: Various systems, methods, and devices are provided for focusing particles suspended within a moving fluid into one or more localized stream lines. The system can include a substrate and at least one channel provided on the substrate having an inlet and an outlet. The system can further include a fluid moving along the channel in a laminar flow having suspended particles and a pumping element driving the laminar flow of the fluid. The fluid, the channel, and the pumping element can be configured to cause inertial forces to act on the particles and to focus the particles into one or more stream lines.

Abstract: 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.

Abstract: The present invention provides systems, apparatuses, and methods to detect the presence of fetal cells when mixed with a population of maternal cells in a sample and to test fetal abnormalities, i.e. aneuploidy. In addition, the present invention provides methods to determine when there are insufficient fetal cells for a determination and report a non-informative case. The present invention involves quantifying regions of genomic DNA from a mixed sample. More particularly the invention involves quantifying DNA polymorphisms from the mixed sample.

Abstract: Extracting and concentrating particles from a first fluid sample includes: providing the first fluid sample to a fluid exchange module of a microfluidic device, providing a second fluid sample to the fluid exchange module, in which the first fluid sample and the second fluid sample are provided under conditions such that particle-free portions of the first fluid sample are shifted, and an inertial lift force causes the particles in the first fluid sample to cross streamlines and transfer into the second fluid sample; passing the second fluid sample containing the transferred particles to a particle concentration module under conditions such that particle-free portions of the second fluid sample are shifted, and such that the particles within the second fluid sample are focused to a streamline within the particle concentration module.

Abstract: 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.

Abstract: The present invention generally relates to methods and compositions to determine viability of an organ for transplantation and other medical purposes. One aspect of the invention relates to a method for assessing the viability of an organ by measuring the energy parameters to determine the energy level of the organ by determining the stored cellular energy (e.g., ATP levels), and/or energy consumption over a particular time period of viability. The energy parameters can be compared to reference energy parameters as a highly accurate and reliable prediction of viable cell yield, and organ viability. Another aspect of the invention relates methods to preserve or extend the time period of viability of an organ any combination of (i) preservation perfusion of the organ to prevent ischemic damage, (ii) chemical metabolic suppression of the organ e.g., using metabolic suppressants, (iii) metabolic suppression by physical or environmental conditions, e.g., sub-zero non-freezing storage.

Abstract: Various systems, methods, and devices are provided for focusing particles suspended within a moving fluid into one or more localized stream lines. The system can include a substrate and at least one channel provided on the substrate having an inlet and an outlet. The system can further include a fluid moving along the channel in a laminar flow having suspended particles and a pumping element driving the laminar flow of the fluid. The fluid, the channel, and the pumping element can be configured to cause inertial forces to act on the particles and to focus the particles into one or more stream lines.

Abstract: 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.

Abstract: This disclosure relates to methods and devices to count particles of interest, such as cells. The methods include obtaining a fluid sample that may contain particles of interest; counting all types of particles in a portion of the sample using a first electrical differential counter to generate a first total; removing any particles of interest from the portion of the fluid sample; counting any particles remaining in the portion of the fluid sample using a second electrical differential counter after the particles of interest are removed to generate a second total; and calculating a number of particles of interest originally in the fluid sample by subtracting the second total from the first total, wherein the difference is the number of particles of interest in the sample. These methods and related devices can be used, for example, to produce a robust, inexpensive diagnostic kit for CD4+ T cell counting in whole blood samples.

Abstract: A microfluidic device includes a particle sorting region having a first, second and third microfluidic channels, a first array of islands separating the first microfluidic channel from the second microfluidic channel, and a second array of islands separating the first microfluidic channel from the third microfluidic channel, in which the island arrays and the microfluidic channels are arranged so that a first fluid is extracted from the first microfluidic channel into the second microfluidic channel and a second fluid is extracted from the third microfluidic channel into the first microfluidic channel, and so that particles are transferred from the first fluid sample into the second fluid sample within the first microfluidic channel.

Abstract: The present invention relates to methods for detecting, enriching, and analyzing rare cells that are present in the blood, e.g. fetal cells. The invention further features methods of analyzing rare cell(s) to determine the presence of an abnormality, disease or condition in a subject, e.g. a fetus by analyzing a cellular sample from the subject.

Abstract: Microfluidic devices and methods for the encapsulation of particles within liquid droplets are disclosed. The new methods and devices form 1-100 picoliter-size monodisperse droplets containing the particles, such as single cells, encapsulated in individual liquid droplets. The particles can be encapsulated in droplets of a fluid by passing a fluid containing the particles through a high aspect-ratio microchannel to order the particles in the fluid, followed by forming the fluid into droplets. The resulting fraction of the liquid droplets with a single particle (e.g., a cell) is higher than the corresponding fraction of single-particle liquid droplets predicted by Poisson statistics.

Abstract: Microfluidic devices are described that include a microfluidic channel, a first array of one or more magnets above the microfluidic channel, each magnet in the first array having a magnetic pole orientation opposite to a magnetic pole orientation of an adjacent magnet in the first array, and a second array of one or more magnets beneath the microfluidic channel, each magnet in the second array having a magnetic pole orientation opposite to a magnetic pole orientation of an adjacent magnet in the second array. The first array is aligned with respect to the second array such that magnetic fields emitted by the first array and second array generate a magnetic flux gradient profile extending through the channel. An absolute value of the profile includes a first maximum and a second maximum that bound a local minimum. The local minimum is located within the microfluidic channel or less than 5 mm away from a wall of the microfluidic channel. Methods of using the new devices are also described.

Abstract: 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.

Abstract: A microfluidic device includes: a first microfluidic channel; a second microfluidic channel extending along the first microfluidic channel; and a first array of islands separating the first microfluidic channel from the second microfluidic channel, in which each island is separated from an adjacent island in the array by an opening that fluidly couples the first microfluidic channel to the second microfluidic channel, in which the first microfluidic channel, the second microfluidic channel, and the islands are arranged so that a fluidic resistance of the first microfluidic channel increases relative to a fluidic resistance of the second microfluidic channel along a longitudinal direction of the first microfluidic channel such that, during use of the microfluidic device, a portion of a fluid sample flowing through the first microfluidic channel passes through one or more of the openings between adjacent islands into the second microfluidic channel.

Abstract: One example of systems and methods for inertio-elastic focusing of particles in microchannels includes a substrate including a channel having an inlet and an outlet. A viscoelastic fluid, i.e., a fluid having a dynamic viscosity that varies with shear rate, and that carries suspended particles is driven through the channel. The volumetric flow rate at which the fluid is driven results in the formation of a localized pathline in the fluid at or near a center of the channel. The localized pathline defines a width that is equal to or slightly greater than a hydraulic diameter of the particle. The particles in the fluid are focused into the localized pathline.

Abstract: Various systems, methods, and devices are provided for focusing particles suspended within a moving fluid into one or more localized stream lines. The system can include a substrate and at least one channel provided on the substrate having an inlet and an outlet. The system can further include a fluid moving along the channel in a laminar flow having suspended particles and a pumping element driving the laminar flow of the fluid. The fluid, the channel, and the pumping element can be configured to cause inertial forces to act on the particles and to focus the particles into one or more stream lines.

Abstract: Methods and devices for evaluating coagulation are described, including methods and devices for detecting an anticoagulant agent or a coagulation abnormality. In various embodiments, the methods and devices of the invention measure coagulation of a sample in response to a gradient of one or more coagulation factors. These responses can be evaluated to accurately profile coagulation impairments of the sample, including the presence of anticoagulant medication. In various embodiments, the invention provides point-of-care or bedside testing with a convenient, microfluidic device that can be used by minimally trained personnel.

Abstract: 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.

Abstract: Microfluidic devices are described that include a microfluidic channel, a first array of one or more magnets above the microfluidic channel, each magnet in the first array having a magnetic pole orientation opposite to a magnetic pole orientation of an adjacent magnet in the first array, and a second array of one or more magnets beneath the microfluidic channel, each magnet in the second array having a magnetic pole orientation opposite to a magnetic pole orientation of an adjacent magnet in the second array. The first array is aligned with respect to the second array such that magnetic fields emitted by the first array and second array generate a magnetic flux gradient profile extending through the channel. An absolute value of the profile includes a first maximum and a second maximum that bound a local minimum. The local minimum is located within the microfluidic channel or less than 5 mm away from a wall of the microfluidic channel. Methods of using the new devices are also described.