Abstract:
A system for deforming and analyzing particles includes a substrate defining an inlet, and an outlet; a fluidic pathway fluidly coupled to the inlet and the outlet and defining a delivery region upstream of a deformation region configured to deform particles, wherein the fluidic pathway comprises a first branch configured to generate a first flow, and a second branch configured to generate a second flow that opposes the first flow, wherein an intersection of the first flow and the second flow defines the deformation region; a detection module including a sensor configured to generate a morphology dataset characterizing deformation of the particles, and a photodetector configured to generate a fluorescence dataset characterizing fluorescence of the particles; and a processor configured to output an analysis of the plurality of particles based at least in part on the deformation dataset and the fluorescent dataset for the plurality of particles.
Abstract:
Apparatus and methods are provided for analysis of individual particles in a microfluidic device. The methods involve the immobilization of an array of particles in suspension and the application of experimental compounds. Such methods can also include electrophysiology studies including patch clamp recording, electroporation, or both in the same microfluidic device. The apparatus provided includes a microfluidic device coupled to a multi-well structure and an interface for controlling the flow of media within the microchannel device.
Abstract:
The present invention provides structures and methods that allow polymers of any length, including nucleic acids containing entire genomes, to be stretched into a long, linear conformation for further analysis. The present invention also provides structures and methods for selecting and stretching polymers based on their lengths. Polymers are loaded into a device and run through the structures. Stretching is achieved by, e.g., applying shear forces as the polymer passes through the structures, placing obstacles in the path of the polymer, or a combination thereof. Since multiple molecules may be stretched in succession, extremely high throughput screening, e.g., screening of more than one molecule per second, is achieved.
Abstract:
A method for determining the length and velocity of single elongated macromolecules is disclosed. In particular, the present invention relates to methods and apparatus for determining the velocity of elongated polymeric molecules moving relative to one or more detection stations, as well as to methods and apparatus for determining the length of such molecules and the distance between landmarks that may be present on such molecules. The invention makes use of time correlated measurements of signal amplitude profiles that result from interactions between each detection station and portions of each macromolecule.
Abstract:
A system for deforming and analyzing a plurality of particles carried in a sample volume includes a substrate defining an inlet, configured to receive the sample volume, and an outlet; and a fluidic pathway fluidly coupled to the inlet and the outlet. The fluidic pathway includes a delivery region configured to receive the plurality of particles from the inlet and focus the plurality of particles from a random distribution to a focused state, a deformation region defining an intersection located downstream of the delivery region and coupled to the outlet, and wherein the deformation region is configured to receive the plurality of particles from the delivery region and to transmit each particle in the plurality of particles into the intersection from a single direction, a first branch fluidly coupled to the deformation region and configured to transmit a first flow into the intersection, and a second branch fluidly coupled to the deformation region and configured to transmit a second flow, substantially opposing the first flow, into the intersection, wherein the first flow and the second flow are configured to induce extension of one or more particles in the plurality of particles.
Abstract:
The invention relates to a measuring device (10) for measuring physical characteristics of cells. The device (10) comprises: a microfluidic chip (20) provided with a flow channel (22) for allowing cells to flow through; a manipulator (24) configured to apply deformation force to a cell in a continuous flow; and a sensor (26) configured to sense a physical characteristic of the cell. The manipulator (24) and the sensor (26) are configured to define a width (W2) of the flow channel (22) as a gap formed between them. The manipulator (24) is configured to apply the deformation force to the cell by compressing the cell against the sensor (26).
Abstract:
In some examples, a system including a fluid stream monitoring system. The monitoring system includes an illumination device configured to illuminate at least some of particles suspended in a fluid stream; and an imaging device configured to image the illuminated particles at a first image plane that intersects a longitudinal axis of the fluid stream, wherein the illumination device and the imaging device are registered to the fluid stream delivery device in the first image plane, where the first image plane is substantially orthogonal to the longitudinal axis. The system includes processing circuitry configured to determine one or more physical characteristics of the fluid particles.
Abstract:
Disclosed is a method for analysing cells, in which cells are separated and the individual cells pass via a measurement region of a unit for spatially resolved radiation intensity measurement, wherein, for at least one of the separated cells, when passing via the measurement region, a time sequence of spatial intensity patterns of an electromagnetic radiation emitted from and/or influenced by the cell is created, the optical flow of a respective two of the spatial intensity patterns is calculated for at least one portion of the sequence of intensity patterns using a computer unit, and an evaluation of the calculated optical flows occurs. Also disclosed is a device for analysing cells, comprising a device for separating cells, a unit for spatially resolved radiation intensity measurement, and a computer unit for calculating the optical flow of a respective two of the created intensity patterns, and for evaluating the calculated optical flows.
Abstract:
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.
Abstract:
A system for deforming and analyzing a plurality of particles carried in a sample volume includes a substrate defining an inlet, configured to receive the sample volume, and an outlet; and a fluidic pathway fluidly coupled to the inlet and the outlet. The fluidic pathway includes a delivery region configured to receive the plurality of particles from the inlet and focus the plurality of particles from a random distribution to a focused state, a deformation region defining an intersection located downstream of the delivery region and coupled to the outlet, and wherein the deformation region is configured to receive the plurality of particles from the delivery region and to transmit each particle in the plurality of particles into the intersection from a single direction, a first branch fluidly coupled to the deformation region and configured to transmit a first flow into the intersection, and a second branch fluidly coupled to the deformation region and configured to transmit a second flow, substantially opposing the first flow, into the intersection, wherein the first flow and the second flow are configured to induce extension of one or more particles in the plurality of particles.