Abstract: The present invention provides, among other aspects, functionalized chromophoric polymer dots comprising a hydrophobic core and a hydrophilic cap, and bioconjugates thereof. Also provided are improved methods for preparing functionalized chromophoric polymer dots. Methods for in vivo imaging and molecular labeling are also disclosed.

Abstract: Provided herein, among other aspects, are methods and apparatuses for ranking aliquots from a suspension containing bioparticles. In certain embodiments, the bioparticles may be cells, organelles, proteins, DNAs, debris of biological origin, microbeads coated with biological compounds, or viral particles. As such, the methods and apparatuses provided herein may be used to quantify rare cells such as circulating cancer cells, fetal cells and other rare cells present in bodily fluids for disease diagnosis, prognosis, or treatment.

Abstract: This document discloses, among other things, a method and system for a substrate having a bypass region for fluid flow. The substrate includes a plurality of fluid flow channels with each channel configured to concurrently allow fluid flow while precluding passage of a target particle or object.

Abstract: Methods and devices are provided for overcoming detrimental diffusive effects in a sample liquid stream by forming segmented liquid bodies (e.g., droplets) from a sample liquid stream in an immiscible liquid stream. The liquid bodies are formed at the intersection of a channel providing the sample liquid stream and a channel providing the immiscible liquid stream. The formed liquid bodies compartmentalize the portion of the sample liquid stream from which the liquid bodies are formed, thus minimizing the detrimental effects of diffusion that occur in a continuous liquid stream.

Abstract: Embodiments of the present invention relate to a UV-curable polyurethane-methacrylate (PUMA) substrate for manufacturing microfluidic devices. PUMA is optically transparent, biocompatible, and has stable surface properties. Embodiments include two production processes that are compatible with the existing methods of rapid prototyping, and characterizations of the resultant PUMA microfluidic devices are presented. Embodiments of the present invention also relate to strategies to improve the production yield of chips manufactured from PUMA resin, especially for microfluidic systems that contain dense and high-aspect-ratio features. Described is a mold-releasing procedure that minimizes motion in the shear plane of the microstructures. Also presented are simple yet scalable able methods for forming seals between PUMA substrates, which avoids excessive compressive force that may crush delicate structures. Two methods for forming interconnects with PUMA microfluidic devices are detailed.

Abstract: A method for quantifying fluorescent puncta comprising acquiring at least one first intensity distribution comprising fluorescence intensity values from a plurality of first fluorescent puncta; acquiring at least one second intensity distribution comprising fluorescence intensity values from a plurality of second fluorescent puncta, wherein each second fluorescent puncta has a determined number of fluorescent emitters; determining the relationship between the first and second intensity distributions; and fitting the second intensity distribution to the first intensity distribution to provide a count and distribution of the number of fluorescent emitters within the first fluorescent puncta.

Abstract: Embodiments in accordance with the present invention relate to methods and apparatuses for concentrating and isolating Circulating Tumor Cells (CTCs) from body fluids. One embodiment of the present invention includes a micro-fabricated or nano-fabricated device having channels configured for separating and excluding. Embodiments in accordance with the present invention utilize features that reduce the hydrodynamic pressure experienced by the cells during the separation, isolation and concentration processes, and therefore reduce the likelihood of cell lysis or other damage to the cells.

Abstract: The present invention relates to microfluidic systems, including valves and pumps for microfluidic systems. The valves of the invention include check valves such as diaphragm valves and flap valves. Other valves of the invention include one-use valves. The pumps of the present invention include a reservoir and at least two check valves. The reservoir may be of variable volume. The present invention also relates to a flexible microfluidic system. The present invention additionally relates to a method of making microfluidic systems including those of the present invention. The method includes forming a microfluidic system on a master, connecting a support to the microfluidic system and removing the microfluidic system from the master. The support may remain connected to the microfluidic system or the microfluidic system may be transferred to another substrate. The present invention further relates to a method of manipulating a flow of a fluid in a microfluidic system.

Abstract: Embodiments in accordance with the present invention relate to the use of effusive filtration to segregate tumor cells from a sample of bodily fluid. In one embodiment, fluid containing a cell is flowed down a channel having a filtration medium present along at least one side wall. The tumor cell is captured when the fluid passes through the filtration medium. Accumulated pressure on the captured tumor cell is reduced by allowing the fluid that has passed through the filtration medium to re-enter the channel. In a particular embodiment, the filtration medium may comprise side wall apertures having a width smaller than that of the cell, with downstream apertures allowing re-entry of the fluid into the channel.

Abstract: Embodiments in accordance with the present invention relate to methods and apparatuses for concentrating and isolating Circulating Tumor Cells (CTCs) from body fluids. One embodiment of the present invention includes a micro-fabricated or nano-fabricated device having channels configured for separating and excluding. Embodiments in accordance with the present invention utilize features that reduce the hydrodynamic pressure experienced by the cells during the separation, isolation and concentration processes, and therefore reduce the likelihood of cell lysis or other damage to the cells.

Abstract: A method and system for performing biochemical detection or analysis on micro- and nano-scale subcellular component within a single biological cell is provided. An integrated platform device and method to perform the biochemical analysis is also provided.

Abstract: Embodiments of the present invention relate to methods and apparatuses for the discretization and manipulation of sample volumes that is simple, robust, and versatile. It is a fluidic device that partitions a sample by exploiting the interplay between fluidic forces, interfacial tension, channel geometry, and the final stability of the formed droplet and/or discretized volume. These compartmentalized volumes allow for isolation of samples and partitioning into a localized array that can subsequently be manipulated and analyzed.

Abstract: Methods and devices are provided for overcoming detrimental diffusive effects in a sample liquid stream by forming segmented liquid bodies (e.g., droplets) from a sample liquid stream in an immiscible liquid stream. The liquid bodies are formed at the intersection of a channel providing the sample liquid stream and a channel providing the immiscible liquid stream. The formed liquid bodies compartmentalize the portion of the sample liquid stream from which the liquid bodies are formed, thus minimizing the detrimental effects of diffusion that occur in a continuous liquid stream.

Abstract: Embodiments of the present invention employ complexly shaped, high-surface-area channels for separation and purification of molecules, including important biopolymers such as proteins, glycoproteins, polysaccharides, and other molecular components of living cells. The relatively large internal surface areas of the complexly shaped channels employed in embodiments of the present invention provide, in comparison to traditional, simply shaped separation channels, increased heat dissipation during electrokinetic separation, and a decreased tendency for bulk-solution flow. Heat dissipation prevents high temperatures that can denature proteins and that can induce thermal currents within the separation channel. Bulk-solution flow within a separation channel can overwhelm the generally linear, electrical-potential-induced migration of molecules that leads to efficient and well-resolved molecular separations.

Abstract: The invention provides a system, system components, and a method for rapidly obtaining and stably maintaining a cell in optimal contact with the cell-contacting surface of a sensor in a cell-based biosensor. In one aspect, the system maximizes the seal between a whole cell and the cell-contact surface of a patch clamp micropipette, maximizing the efficiency of a whole cell patch clamp recording.

Abstract: Embodiments in accordance with the present invention relate to the use of effusive filtration to segregate tumor cells from a sample of bodily fluid. In one embodiment, fluid containing a cell is flowed down a channel having a filtration medium present along at least one side wall. The tumor cell is captured when the fluid passes through the filtration medium. Accumulated pressure on the captured tumor cell is reduced by allowing the fluid that has passed through the filtration medium to re-enter the channel. In a particular embodiment, the filtration medium may comprise side wall apertures having a width smaller than that of the cell, with downstream apertures allowing re-entry of the fluid into the channel.

Abstract: Capsules that include a shell, a sensitizer, and an active material. Methods for using the capsules to spatiotemporally deliver active material. Representative shells include vesicles, polymers, and inorganic materials. Representative active materials include small molecules and proteins.

Abstract: Embodiments in accordance with the present invention relate to methods and apparatuses for concentrating and isolating Circulating Tumor Cells (CTCs) from body fluids. One embodiment of the present invention includes a micro-fabricated or nano-fabricated device having channels configured for separating and excluding. Embodiments in accordance with the present invention utilize features that reduce the hydrodynamic pressure experienced by the cells during the separation, isolation and concentration processes, and therefore reduce the likelihood of cell lysis or other damage to the cells.

Abstract: The invention provides a system, system components, and a method for rapidly obtaining and stably maintaining a cell in optimal contact with the cell-contacting surface of a sensor in a cell-based biosensor. In one aspect, the system maximizes the seal between a whole cell and the cell-contact surface of a patch clamp micropipette, maximizing the efficiency of a whole cell patch clamp recording.

Abstract: The present invention provides, in certain embodiments, improved microfluidic systems and methods for fabricating improved microfluidic systems, which contain one or more levels of microfluidic channels. The inventive methods can provide a convenient route to topologically complex and improved microfluidic systems. The microfluidic systems provided according to the invention can include three-dimensionally arrayed networks of fluid flow paths therein including channels that cross over or under other channels of the network without physical intersection at the points of cross over. The microfluidic networks of the invention can be fabricated via replica molding processes, also provided by the invention, utilizing mold masters including surfaces having topological features formed by photolithography.