Apparatuses for flowing multiple fluids in a single channel while substantially maintaining fluid separation are disclosed. In one configuration, the apparatus includes a first internal surface portion with an affinity to a first fluid and a second internal surface portion with an affinity to a second fluid. In another configuration, the apparatus includes a first fluid channel portion, a second fluid channel portion wrapped helically around the first fluid channel portion, and an opening therebetween. Also disclosed is an apparatus for maintaining substantially even fluid flow in fluid pathways having a first flow resistor portion, a second flow resistor portion, and a fluid channel therebetween.

The present invention relates to a device and method for high-throughput single cell stretching with the hydrodynamic force for assessing cellular mechanical properties. In an aspect of the invention, there is provided a uniquely designed microfluidic channel flowing with viscoelastic fluids, sensing electrodes integrated with the microchannel and a high-speed imaging and processing system. Cells are continuously pumped in the device, aligned and stretched. The arrival of individual cells prior to the cell stretching site can be detected by the electrical sensing unit, which produces a triggering signal to activate a high-speed camera for on-demand imaging of the cell motion and deformation. Cellular mechanical properties including cell size and cell deformability are extracted from the analysis of these captured single cell images.

Methods, devices, and systems for performing isoelectric focusing reactions are described. The systems or devices disclosed herein may comprise fixtures that have a membrane. In some instances, the disclosed devices may be designed to perform isoelectric focusing or other separation reactions followed by further characterization of the separated analytes using mass spectrometry. The disclosed methods, devices, and systems provide for fast, accurate separation and characterization of protein analyte mixtures or other biological molecules by isoelectric point.

A system is disclosed that enables the automated measurement of cellular mechanical parameters at high throughputs. The microfluidic device uses intersecting flows to create an extensional flow region where the cells undergo controlled stretching. Cells are focused into streamlines prior to entering the extensional flow region. In the extensional region, each cell's deformation is measured with an imaging device. Automated image analysis extracts a range of independent biomechanical parameters from the images. These may include cell size, deformability, and circularity. The single cell data that is obtained may then be used to in a variety of ways. Scatter density plots of deformability and circularity may be developed and displayed for the user. Mechanical parameters such as deformability and circularity may be gated or thresholded to identify certain cells of interest or sub-populations of interest. Similarly, the mechanical data obtained using the device may be used as cell signatures.

In the present technology, the timing at which suction is performed is optimized in order to enhance the microparticle separation performance in a technology for separating target microparticles in a microchip. For this purpose, the present technology provides a method of optimizing a microparticle suction condition, and the like, using a microchip having a main flow channel through which a liquid containing a microparticle flows, a microparticle suction flow channel arranged coaxially with the main flow channel, and a branch flow channel branching from the main flow channel. The method includes: a branch point specifying process of specifying a branch point at which the branch flow channel branches from the main flow channel; and a time assignment process of assigning a time T.sub.1 to be applied to suction of the microparticle.

A system is disclosed that enables the automated measurement of cellular mechanical parameters at high throughputs. The microfluidic device uses intersecting flows to create an extensional flow region where the cells undergo controlled stretching. Cells are focused into streamlines prior to entering the extensional flow region. In the extensional region, each cell's deformation is measured with an imaging device. Automated image analysis extracts a range of independent biomechanical parameters from the images. These may include cell size, deformability, and circularity. The single cell data that is obtained may then be used to in a variety of ways. Scatter density plots of deformability and circularity may be developed and displayed for the user. Mechanical parameters such as deformability and circularity may be gated or thresholded to identify certain cells of interest or sub-populations of interest. Similarly, the mechanical data obtained using the device may be used as cell signatures.

A microfluidic chip orients and isolates components in a sample fluid mixture by two-step focusing, where sheath fluids compress the sample fluid mixture in a sample input channel in one direction, such that the sample fluid mixture becomes a narrower stream bounded by the sheath fluids, and by having the sheath fluids compress the sample fluid mixture in a second direction further downstream, such that the components are compressed and oriented in a selected direction to pass through an interrogation chamber in single file formation for identification and separation by various methods. The isolation mechanism utilizes external, stacked piezoelectric actuator assemblies disposed on a microfluidic chip holder, or piezoelectric actuator assemblies on-chip, so that the actuator assemblies are triggered by an electronic signal to actuate jet chambers on either side of the sample input channel, to jet selected components in the sample input channel into one of the output channels.

The invention describes a method for isolating one or more genetic elements encoding a gene product having a desired activity, comprising the steps of: (a) compartmentalising genetic elements into microcapsules; and (b) sorting the genetic elements which express the gene product having the desired activity; wherein at least one step is under microfluidic control. The invention enables the in vitro evolution of nucleic acids and proteins by repeated mutagenesis and iterative applications of the method of the invention.

Systems and methods for manipulating and/or investigating objects, in particular biological objects such as cellular bodies, in a sample holder are provided. The sample holder comprises a holding space for holding a sample comprising one or more objects in a fluid medium. An acoustic wave generator is connected with the sample holder to generate an acoustic wave in the holding space exerting a force on at least part of the sample. Fluid flows through microfluidic channels in the sample holder and acoustic waves are controlled.

A method of sorting cellular bodies comprises receiving images representing manipulation of first cellular bodies in a holding space of a flow cell including or connected to a sorting device, the manipulation including: allowing some of the first cellular bodies to contact a functionalized wall of the holding space; applying a force to the contacted first cellular bodies for detaching some of the first cellular bodies; and, transporting the cellular bodies to the sorting device; and, processing the sequence of images of the first cellular bodies and controlling the sorting device based on the image processing by detecting detachments of first cellular bodies in the images; determining for each detected detached first cell a detachment force; tracking the location of detached first cellular bodies during the transport of the cellular bodies to the sorting device; and, sorting the cellular bodies by controlling the sorting device based on the detachment force.