41 results about "Hydrodynamic focusing" patented technology

A microfluidic device comprises inlets for a sample flow and an out-of-plane focusing sheath flow, and a curved channel section configured to receive the sample flow and out-of-plane focusing sheath and to provide hydrodynamic focusing of the sample flow in an out-of-plane direction, the out-of-plane direction being normal to a plane including the curved channel. Examples of the invention also include improved flow cytometers.

A microfluidic apparatus having a one-dimensional or two-dimensional hydrodynamic flow system to control stable and proper digitally coded bead orientation through the optical detection area of a bioanalysis system. The hydrodynamic system include one core flow, which carries the rectangular barcode beads, and sheath flows, on the sides of or about or around the outer periphery of the core flow, pull the core flow into a proper orientation. The sheath flows, at much higher flow speed but lower volume flow rate, can be pushed or pulled by vacuum, gravity, or pressure. By this method, the coded bead will align themselves in line and flow reliably, without wobbling or flipping, in the core flow channel through the detection zone. By adjusting the relative flow rate of core flow and sheath flows, the coded beads flow reliably in the flow system, thus it can be decoded and detected by an optical system accurately.

Disclosed herein are methods, apparatuses, and systems for performing nucleic acid sequencing reactions and molecular binding reactions in a microfluidic channel. The methods, apparatuses, and systems can include a restriction barrier to restrict movement of a particle to which a nucleic acid is attached. Furthermore, the methods, apparatuses, and systems can include hydrodynamic focusing of a delivery flow. In addition, the methods, apparatuses, and systems can reduce non-specific interaction with a surface of the microfluidic channel by providing a protective flow between the surface and a delivery flow.

A microfluidic device comprises inlets for a sample flow and an out-of-plane focusing sheath flow, and a curved channel section configured to receive the sample flow and out-of-plane focusing sheath and to provide hydrodynamic focusing of the sample flow in an out-of-plane direction, the out-of-plane direction being normal to a plane including the curved channel.

The present disclosure relates to microfluidic devices adapted for facilitating cytometry analysis of particles flowing therethrough. In certain embodiments, the microfluidic devices allow light collection from multiple directions. In certain other embodiments, the microfluidic devices use spatial intensity modulation. In certain other embodiments, the microfluidic devices have magnetic field separators. In certain other embodiments, the microfluidic devices have the ability to stack. In certain other embodiments, the microfluidic devices have 3-D hydrodynamic focusing to align sperm cells. In certain other embodiments, the microfluidic devices have acoustic energy couplers. In certain other embodiments, the microfluidic devices have phase variation producing lenses. In certain other embodiments, the microfluidic devices have transmissive and reflective lenses. In certain other embodiments, the microfluidic devices have integrally-formed optics. In certain other embodiments, the microfluidic devices have non-integral geographically selective reagent delivery structures. In certain other embodiments, the microfluidic devices have optical waveguides incorporated into their flow channels. In certain other embodiments, the microfluidic devices have optical waveguides with reflective surfaces incorporated into their flow channels. In certain other embodiments, the microfluidic devices have virus detecting and sorting capabilities. In certain other embodiments, the microfluidic devices display a color change to indicate use or a result.

Disclosed herein are methods, apparatuses, and systems for performing nucleic acid sequencing reactions and molecular binding reactions in a microfluidic channel. The methods, apparatuses, and systems can include a restriction barrier to restrict movement of a particle to which a nucleic acid is attached. Furthermore, the methods, apparatuses, and systems can include hydrodynamic focusing of a delivery flow. In addition, the methods, apparatuses, and systems can reduce non-specific interaction with a surface of the microfluidic channel by providing a protective flow between the surface and a delivery flow.

A microfluidic device comprises inlets for a sample flow and an out-of-plane focusing sheath flow, and a curved channel section configured to receive the sample flow and out-of-plane focusing sheath and to provide hydrodynamic focusing of the sample flow in an out-of-plane direction, the out-of-plane direction being normal to a plane including the curved channel.

Hydrodynamic focusing of two fluid steams provides a novel micro printing technology for printed electronics and other high performance applications.

A microfluidic device comprises inlets for a sample flow and an out-of-plane focusing sheath flow, and a curved channel section configured to receive the sample flow and out-of-plane focusing sheath and to provide hydrodynamic focusing of the sample flow in an out-of-plane direction, the out-of-plane direction being normal to a plane including the curved channel. Examples of the invention also include improved flow cytometers.

Disclosed herein are methods, apparatuses, and systems for performing nucleic acid sequencing reactions and molecular binding reactions in a microfluidic channel. The methods, apparatuses, and systems can include a restriction barrier to restrict movement of a particle to which a nucleic acid is attached. Furthermore, the methods, apparatuses, and systems can include hydrodynamic focusing of a delivery flow. In addition, the methods, apparatuses, and systems can reduce non-specific interaction with a surface of the microfluidic channel by providing a protective flow between the surface and a delivery flow.

The invention provides an apparatus and methods for label-free, chemical specific detection in flow for high throughput characterization of analytes in applications such as flow injection analysis, electrophoresis, and chromatography. A surface-enhanced Raman scattering (SERS) flow detector capable of ultrasensitive optical detection on the millisecond time scale has been developed. The device employs hydrodynamic focusing to improve SERS detection in a flow channel where a sheath flow confines analyte molecules eluted from a capillary over a planar SERS-active substrate. Increased analyte interactions with the SERS substrate significantly improve detection sensitivity. Raman experiments at different sheath flow rates showed increased sensitivity compared with the modeling predictions, indicating increased adsorption. At low analyte concentrations, rapid analyte desorption is observed, enabling repeated and high-throughput SERS detection. The flow detector offers substantial advantages over conventional SERS-based assays such as minimal sample volumes and high detection efficiency.

The present invention is a flow cell and method for use in microfluidic analyses that presents highly discrete and small volumes of fluid to isolated locations on a two-dimensional surface contained within an open fluidic chamber defined by the flow cell that has physical dimensions such that laminar style flow occurs for fluids flowing through the chamber. This process of location specific fluid addressing within the flow cell is facilitated by combining components of hydrodynamic focusing with site specific cell evacuation. The process does not require the use of physical barriers within the flow cell or mechanical valves to control the paths of fluid movement.

A microfluidic chip having a micro channel for processing a sample is provided. The micro channel may focus the sample by using focusing fluid and a core stream forming geometry. The core stream forming geometry may include a lateral fluid focusing component and one or more vertical fluid focusing components. A microfluidic chip may include a plurality micro channels operating in parallel on a microfluidic chip.

In a method for hydrodynamic focusing of a laminar and planar sample fluid flow, a system is provided for analysis and / or sorting of microscopic objects in the sample fluid comprising an optical objective for optical inspection of the microscopic objects. Microscopic objects are conveyed in the laminar flow of the sample fluid, and two laminar and planar flow of sheath fluids are provided. The flow of the sample fluid is hydrodynamically focused at an optical inspection zone of the system by the sheath fluids. Focusing of the flow of the sample fluid is controlled such that all of the microscopic objects in the sample fluid are caused to be conveyed in a common flow direction in one single plane at the inspection zone of the system, and the microscopic objects in the fluid are optically inspected through the optical objective.

In a method for hydrodynamic focusing of a laminar and planar sample fluid flow, a system is provided for analysis and / or sorting of microscopic objects in the sample fluid comprising an optical objective for optical inspection of the microscopic objects. Microscopic objects are conveyed in the laminar flow of the sample fluid, and two laminar and planar flow of sheath fluids are provided. The flow of the sample fluid is hydrodynamically focused at an optical inspection zone of the system by the sheath fluids. Focusing of the flow of the sample fluid is controlled such that all of the microscopic objects in the sample fluid are caused to be conveyed in a common flow direction in one single plane at the inspection zone of the system, and the microscopic objects in the fluid are optically inspected through the optical objective.

Disclosed is a method for detecting nano-particles, comprising the steps of (1) compressing a sample liquid to be tested into a sample liquid flow by hydrodynamic focusing using a sheath fluid; (2) irradiating a measuring light to the sample liquid flow, wherein a single nano-particle in the sample liquid flow is irradiated by the measuring light for a duration of 0.1-10 milliseconds; (3) defining the area in which the measuring light irradiates the sample liquid flow as a detecting area, and collecting light signals emitted from the area irradiated by the measuring light by a lens imaging system, and allowing the light signals collected by the lens imaging system to pass a field stop, so as to filter out the light signals outside the detecting area and enrich the light signals from the detecting area; and (4) subjecting the light signals enriched by the field stop to optoelectronic signal conversion. The method can achieve detection for nano-particles with a low refractive index and a particle size of 24-1000 nm as well as nano-scale gold particles with a particle size of 6.7-150 nm.

Methods for selecting chemotherapeutic agents for treating a cancer are provided that include the steps of providing a cancer cell sample having a population of bulk cancer cells and a population of cancer stem-like cells, culturing a first portion of the cancer cell sample in a hydrodynamic focusing bioreactor under microgravity conditions and for a period of time to selectively enhance the population of cancer stem-like cells and selectively kill the population of bulk cancer cells, contacting the cancer stem-like cells with one or more chemotherapeutic agents, and then selecting the one or more chemotherapeutic agents for treating the cancer if there is an increase in an amount of cytotoxicity. Methods for treating a cancer are also provided in which the identified chemotherapeutic agents are administered to a subject. Further provided are methods for identifying a test compound useful for treating a cancer.

Disclosed is a method for detecting nano-particles, comprising the steps of (1) compressing a sample liquid to be tested into a sample liquid flow by hydrodynamic focusing using a sheath fluid; (2) irradiating a measuring light to the sample liquid flow, wherein a single nano-particle in the sample liquid flow is irradiated by the measuring light for a duration of 0.1-10 milliseconds; (3) defining the area in which the measuring light irradiates the sample liquid flow as a detecting area, and collecting light signals emitted from the area irradiated by the measuring light by a lens imaging system, and allowing the light signals collected by the lens imaging system to pass a field stop, so as to filter out the light signals outside the detecting area and enrich the light signals from the detecting area; and (4) subjecting the light signals enriched by the field stop to optoelectronic signal conversion. The method can achieve detection for nano-particles with a low refractive index and a particle size of 24-1000 nm as well as nano-scale gold particles with a particle size of 6.7-150 nm.

An apparatus and method for coating micron-sized or sub-micron-sized particles such as living cells. The coating apparatus includes an encapsulation chamber enclosing a two-layer water-oil system for coating each islet cell with an aqueous polymeric coat. Islets together with an aqueous polymer solution are fed by a feed device that utilizes the principle of hydrodynamic focusing in order to ensure encapsulation of individual islets. The polymer in the aqueous coat is subsequently crosslinked by being exposed to laser light to produce structurally stable microcapsules of controllable thickness of the order of tens of microns. Encapsulated islets are removed from the encapsulation chamber by a valveless pump and recovered by filtration or centrifugation.

The invention discloses a micro-channel structure used for two-dimensional hydrodynamic focusing and a microfluid chip. The micro-channel structure comprises a first sample flow channel, a second sample flow channel, an upper-layer longitudinal focused flow channel, a lower-layer longitudinal focused flow channel, a left transverse focused flow channel and a right transverse focused flow channel, wherein the first sample flow channel and the second sample flow channel are respectively located at the front and the back and are mutually communicated, the upper-layer longitudinal focused flow channel and the lower-layer longitudinal focused flow channel are respectively stacked on the top and the bottom of the first sample flow channel, the left transverse focused flow channel and the right transverse focused flow channel are respectively arranged on at the left and right sides of the second sample flow channel, the rears end of the upper-layer and lower-layer longitudinal focused flow channels are both communicated with the first sample flow channel, and the rears end of the left and right transverse focused flow channels are both communicated with the second sample flow channel. The micro-channel structure used for two-dimensional hydrodynamic focusing has a two-dimensional focusing function, controllable focusing effect and the advantages of low flow resistance, a wide application scope of flow velocity, etc.

The invention provides a hydrodynamic focusing apparatus used for a diffraction imaging flow cytometer. The hydrodynamic focusing apparatus comprises a sheath flow tube, a nuclear flow tube and a fluid chamber made of an optically transparent material, wherein the upper part of the sheath flow tube is located out of the upper port of the fluid chamber, the lower part of the sheath flow tube is embedded into the upper port of the fluid chamber, the lower part of the nuclear flow tube axially penetrates the center of the sheath flow tube from the upper port of the sheath flow tube and is located in the fluid chamber, the upper part of the nuclear flow tube is located out of the upper port of the sheath flow tube, and the lower port of the fluid chamber is provided with a liquid discharging pipe. The cross section of a liquid flow channel in the fluid chamber is a polygon, the outer wall of each edge is a plane, and the fluid chamber is prepared from the optically transparent material through bonding or sintering. According to the invention, processing of the sheath flow tube and the nuclear flow tube is simple; the hydrodynamic focusing apparatus can realize hydrodynamic focusing of nuclear flow in a great flow velocity adjusting range and obtain a stable layer fluid with accurately controllable nuclear flow position and flow velocity, so a high-contrast diffraction image of a to-be-measured particle can be obtained eventually.

An apparatus for microfluidic flow cytometry analysis of a particulate containing fluid An apparatus for microfluidic flow cytometry analysis of a particulate containing fluid comprises a hydrodynamic focussing apparatus for providing a focused stream of particulate containing fluid; and a microfluidic chip. The chip has a plurality of layers and comprises a microfluidic channel that extends through the chip substantially orthogonal to a plane of the layers of the chip, and is in fluid communication with the hydrodynamic focusing apparatus for receipt of a focused steam of particulate containing fluid. The chip also comprises a detection zone comprising at least one pair of electrodes in electrical communication with the microfluidic channel. At least one pair of electrodes comprise an excitation electrode coupled to an AC signal source and a detection electrode configured to detect AC impedance changes in the microfluidic channel between the electrodes resulting from particles passing between the electrodes in the microfluidic channel. Methods of sorting mammalian sperm cells according to sex is also described.

The present invention is a flow cell and method for use in microfluidic analyses that presents highly discrete and small volumes of fluid to isolated locations on a two-dimensional surface contained within an open fluidic chamber defined by the flow cell that has physical dimensions such that laminar style flow occurs for fluids flowing through the chamber. This process of location specific fluid addressing within the flow cell is facilitated by combining components of hydrodynamic focusing with site specific cell evacuation. The process does not require the use of physical barriers within the flow cell or mechanical valves to control the paths of fluid movement.

The invention discloses a micro-channel structure and a micro-fluid chip with the micro-channel structure for achieving two-dimensional fluid power accumulation by using a single-way sheath liquid. The micro-channel structure comprises a sample flow channel, an upper longitudinal accumulated flow channel, a lower longitudinal accumulated flow channel and two transverse accumulated flow channels, wherein the upper longitudinal accumulated flow channel is arranged above the sample flow channel in an overlapped manner; the lower longitudinal accumulated flow channel is arranged below the sample flow channel in the overlapped manner; the two transverse accumulated flow channels are respectively arranged on the left side and right side of the sample flow channel; the width of each transverse accumulated flow channel is gradually reduced from back to front in a liquid flowing direction; and the maximum width of each transverse accumulated flow channel is greater than that of the sample flow channel. According to the micro-channel structure for achieving two-dimensional fluid power accumulation by using the single-way sheath liquid, disclosed by the embodiment of the invention, two-dimensional accumulation of a sample flow can be achieved, the sample flow can be prevented from being dispersed by the sheath liquid, the liquid flow can be kept stable, and the two-dimensional accumulation effect of the sample flow can be ensured.

The invention discloses a multi-mode precisely-focused electrical impedance flow cytometry detection device and a preparation method thereof. The device comprises a non-conductive body, and a hydrodynamic focusing flow channel, an ultrasonic focusing flow channel, an electrical impedance detection flow channel and an outlet flow channel are sequentially arranged in the body in the direction from the fluid inlet to the fluid outlet. The hydrodynamic focusing flow channel comprises a sample flow channel in the middle and a sheath fluid flow channel wrapping the sample flow channel; the sample flow channel is communicated with the sample inlet, the sheath fluid flow channel is communicated with the sheath fluid inlet through the sheath fluid flow inlet flow channel, a piezoelectric element isarranged on the outer side of the ultrasonic focusing flow channel, electrical impedance detection electrodes are arranged at the two ends of the electrical impedance detection flow channel, and double-nozzle 3D printing is adopted in the preparation method. According to the invention, the problem of congestion of a sample particle blocking point is solved, the targets of high focusing speed andaccurate focusing position are realized, rapid, accurate and effective focusing is carried out on cells, and the difficulty of signal processing is reduced.

The invention provides an apparatus and methods for label-free, chemical specific detection in flow for high throughput characterization of analytes in applications such as flow injection analysis, electrophoresis, and chromatography. A surface-enhanced Raman scattering (SERS) flow detector capable of ultrasensitive optical detection on the millisecond time scale has been developed. The device employs hydrodynamic focusing to improve SERS detection in a flow channel where a sheath flow confines analyte molecules eluted from a capillary over a planar SERS-active substrate. Increased analyte interactions with the SERS substrate significantly improve detection sensitivity. Raman experiments at different sheath flow rates showed increased sensitivity compared with the modeling predictions, indicating increased adsorption. At low analyte concentrations, rapid analyte desorption is observed, enabling repeated and high-throughput SERS detection. The flow detector offers substantial advantages over conventional SERS-based assays such as minimal sample volumes and high detection efficiency.

The present disclosure relates to microfluidic devices adapted for facilitating cytometry analysis of particles flowing therethrough. In certain embodiments, the microfluidic devices allow light collection from multiple directions. In certain other embodiments, the microfluidic devices use spatial intensity modulation. In certain other embodiments, the microfluidic devices have magnetic field separators. In certain other embodiments, the microfluidic devices have the ability to stack. In certain other embodiments, the microfluidic devices have 3-D hydrodynamic focusing to align sperm cells. In certain other embodiments, the microfluidic devices have acoustic energy couplers. In certain other embodiments, the microfluidic devices have phase variation producing lenses. In certain other embodiments, the microfluidic devices have transmissive and reflective lenses. In certain other embodiments, the microfluidic devices have integrally-formed optics. In certain other embodiments, the microfluidic devices have non-integral geographically selective reagent delivery structures. In certain other embodiments, the microfluidic devices have optical waveguides incorporated into their flow channels. In certain other embodiments, the microfluidic devices have optical waveguides with reflective surfaces incorporated into their flow channels. In certain other embodiments, the microfluidic devices have virus detecting and sorting capabilities. In certain other embodiments, the microfluidic devices display a color change to indicate use or a result.

The invention discloses a flow chamber of a flow cytometer, and relates to the field of flow cytometers. By adopting the flow chamber, the problems that when the sample feeding rate of a sample flow of an existing flow cytometer is increased, to-be-tested cells or micro-particles are deviated from the central position of an irradiation light spot to cause that the irradiation energy is non-uniform, signal changes are increased, and data quality is reduced, and thus the detection precision of the cytometer is reduced can be solved. The flow chamber comprises an inlet area, a converging area, an adjusting area, a detection area and an auxiliary area, wherein the inlet area is provided with a main sheath liquid inlet, a sample flow inlet and an air pressure adjusting opening, the adjusting area is provided with two adjusting area inlets and a comprehensive adjusting area, main sheath liquid enters the inlet area from the sheath liquid inlet, the sample flow enters the converging area from a sample flow pipe, and the main sheath liquid and the sample flow are converged into a steady laminar flow in the converging area by using hydrodynamic focusing characteristics and then sequentially enter the comprehensive adjusting area, the detection area and the auxiliary area. According to the flow chamber disclosed by the invention, relatively high detection precision can be achieved at both high and low sample flow sample feeding rates, particularly, the nuclear flow diameter obtained after the sample flow is converged can be reduced at a high sample flow sample feeding rate, and high precision can be achieved.

Hydrodynamic focusing of two fluid steams provides a novel micro printing technology for printed electronics and other high performance applications.