US20020172622A1 - Microfluidic device for concentrating particles in a concentrating solution - Google Patents

Microfluidic device for concentrating particles in a concentrating solution Download PDF

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Publication number
US20020172622A1
US20020172622A1 US10/114,765 US11476502A US2002172622A1 US 20020172622 A1 US20020172622 A1 US 20020172622A1 US 11476502 A US11476502 A US 11476502A US 2002172622 A1 US2002172622 A1 US 2002172622A1
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Prior art keywords
concentrating
fluid
channel
particles
sample
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Abandoned
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US10/114,765
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English (en)
Inventor
Bernhard Weigl
Ronald Bardell
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Revvity Health Sciences Inc
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Individual
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Priority to US10/114,765 priority Critical patent/US20020172622A1/en
Publication of US20020172622A1 publication Critical patent/US20020172622A1/en
Assigned to MICRONICS, INC. reassignment MICRONICS, INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: BARDELL, RONALD L., WEIGL, BERNHARD H.
Priority to US11/122,139 priority patent/US20050201903A1/en
Assigned to PERKINELMER HEALTH SCIENCES, INC. reassignment PERKINELMER HEALTH SCIENCES, INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: MICRONICS, INC.
Abandoned legal-status Critical Current

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    • G01N1/40—Concentrating samples
    • G01N1/4005—Concentrating samples by transferring a selected component through a membrane
    • G01N2001/4016—Concentrating samples by transferring a selected component through a membrane being a selective membrane, e.g. dialysis or osmosis
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
    • G01N1/40—Concentrating samples
    • G01N1/4055—Concentrating samples by solubility techniques
    • G01N2001/4061—Solvent extraction
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
    • G01N1/40—Concentrating samples
    • G01N1/4077—Concentrating samples by other techniques involving separation of suspended solids
    • G01N2001/4094—Concentrating samples by other techniques involving separation of suspended solids using ultrasound
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N15/02—Investigating particle size or size distribution
    • G01N2015/0288—Sorting the particles
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N15/10—Investigating individual particles
    • G01N15/14—Optical investigation techniques, e.g. flow cytometry
    • G01N15/1404—Handling flow, e.g. hydrodynamic focusing
    • G01N15/1409—Handling samples, e.g. injecting samples
    • G01N2015/1411—Features of sheath fluids
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N15/10—Investigating individual particles
    • G01N15/14—Optical investigation techniques, e.g. flow cytometry
    • G01N15/1404—Handling flow, e.g. hydrodynamic focusing
    • G01N2015/1413—Hydrodynamic focussing
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    • G01N15/10—Investigating individual particles
    • G01N15/14—Optical investigation techniques, e.g. flow cytometry
    • G01N15/1434—Optical arrangements
    • G01N2015/144—Imaging characterised by its optical setup
    • G—PHYSICS
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    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
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    • G01N15/10—Investigating individual particles
    • G01N15/14—Optical investigation techniques, e.g. flow cytometry
    • G01N2015/1486—Counting the particles
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N2035/00178—Special arrangements of analysers
    • G01N2035/00237—Handling microquantities of analyte, e.g. microvalves, capillary networks
    • G01N2035/00247—Microvalves
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00—Chemistry: analytical and immunological testing
    • Y10T436/25—Chemistry: analytical and immunological testing including sample preparation
    • Y10T436/25375—Liberation or purification of sample or separation of material from a sample [e.g., filtering, centrifuging, etc.]
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00—Chemistry: analytical and immunological testing
    • Y10T436/25—Chemistry: analytical and immunological testing including sample preparation
    • Y10T436/2575—Volumetric liquid transfer

Definitions

  • This invention relates generally to microfluidic devices for performing analytic testing, and, in particular, to a device in which the concentration of a particle in a solvent is increased by flowing it in contact with a solution that extracts solvent.
  • Microfluidic devices have recently become popular for performing analytic testing. Using tools developed by the semiconductor industry to miniaturize electronics, it has become possible to fabricate intricate fluid systems which can be inexpensively means produced. Systems have been developed to perform a variety of analytical techniques for the acquisition of information for the medical field.
  • Microfluidic devices may be constructed in a multi-layer laminated structure where each layer has channels and structures fabricated from a laminate material to form microscale voids or channels where fluids flow.
  • a microscale channel is generally defined as a fluid passage which has at least one internal cross-sectional dimension that is less than 500 ⁇ m and typically between about 0.1 ⁇ m and about 500 ⁇ m. The control and pumping of fluids through these channels is affected by either external pressurized fluid forced into the laminate, or by structures located within the laminate.
  • U.S. Pat. No. 5,716,852 teaches a method for analyzing the presence and concentration of small particles in a flow cell using diffusion principles.
  • This patent discloses a channel cell system for detecting the presence of analyte particles in a sample stream using a laminar flow channel having at least two inlet means which provide an indicator stream and a sample stream, where the laminar flow channel has a depth sufficiently small to allow laminar flow of the streams and length sufficient to allow diffusion of particles of the analyte into the indicator stream to form a detection area, and having an outlet out of the channel to form a single mixed stream.
  • This device which is known at a T-Sensor, may contain an external detecting means for detecting changes in the indicator stream.
  • This detecting means may be provided by any means known in the art, including optical means such as optical spectroscopy, or absorption spectroscopy of fluorescence.
  • U.S. Pat. No. 5,932,100 which patent is also incorporated herein by reference, teaches another method for analyzing particles within microfluidic channels using diffusion principles.
  • a mixture of particles suspended in a sample stream enters an extraction channel from one upper arm of a structure, which comprises microchannels in the shape of an “H”.
  • An extraction stream (a dilution stream) enters from the lower arm on the same side of the extraction channel and due to the size of the microfluidic extraction channel, the flow is laminar and the streams do not mix.
  • the sample stream exits as a by-product stream at the upper arm at the end of the extraction channel, while the extraction stream exits as a product stream at the lower arm.
  • particles having a greater diffusion coefficient small particles such as albumin, sugars, and small ions
  • the larger particles blood cells
  • Particles in the exiting extraction stream may be analyzed without interference from the larger particles.
  • This microfluidic structure commonly known as an “H-Filter,” can be used for extracting desired particles from a sample stream containing those particles.
  • FIG. 1 is a top view of a T-Sensor which operates according to the principles of the present invention.
  • FIG. 2 is a top view of a diffusion channel of an H-Filter which operates according to the principles of the present invention.
  • FIG. 1 shows a standard T-Sensor device, designated at 10 , the operation of which is described in detail in U.S. Pat. No. 5,716,852.
  • T-Sensor 10 consists of a first channel 12 having an input port 18 . Channels 12 and 16 meet at a diffusion channel 20 having an output 21 , as shown in FIG. 1 . The characteristics of T-Sensor 10 are such that fluids from channels 12 and 16 will flow laminarly within diffusion channel 20 .
  • a sample 22 to be concentrated which contains constituents which diffuse more slowly than the sample solvent molecules, is injected into input port 14 , while a concentrating solution 24 is injected into port 18 .
  • the fluids flow through channels 12 and 16 respectively and finally into diffusion channel 20 .
  • Flow within channel 20 is laminar such that a diffusion interface region 26 is formed.
  • Concentrating solution 24 is formulated such that is extracts fluid from sample 22 , and may contain large ionic compounds, such as surfactant molecules, which do not diffusion significantly into the sample stream, whereas sample fluid 22 molecules, typically small solvent molecules such as water, diffuse into concentration solution 24 very quickly, as indicated by arrows A, thus concentrating all molecules contained in sample 22 that have a smaller diffusion coefficient (i.e., a larger size) than the solvent molecules.
  • a sample solution of urine containing bacteria is injected into port 14 , while a concentrating solution such as icodextrin is injected into port 18 . Molecules from the sample diffuse quickly into the icodextrin solution, and at output 21 of T-Sensor 10 , the bacteria would be concentrated in a small volume of fluid.
  • FIG. 2 An alternative embodiment for carrying out the present invention is shown in FIG. 2.
  • the diffusion channel 50 of an H-Filter structure is shown.
  • the velocity distribution of fluid flow in microchannels usually follows a combination of a parabolic flow profile and a plug flow profile, depending on viscosity, flow speed, channel dimensions, etc.
  • the flow profile is more or less uniformly parabolic, whereas for a rectangular cross section, the flow profile is parabolic only in the narrow dimension, and a combination of parabolic (close to the walls) and plug flow (closer to the center of the channel), as shown at 52 in FIG. 2.
  • This effect is frequently enhanced by having a sample with a higher velocity than the receiver solution, thus further slowing down the sample and increasing the separation speed.
  • the separation process can be further increased by providing a large diffusion interface area and a small diffusion distance.
  • separation of fluids having different flow speeds by a permeable membrane within a microchannel will also enhance diffusion across the membrane.

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Dispersion Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Analytical Chemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • Hematology (AREA)
  • Clinical Laboratory Science (AREA)
  • Mechanical Engineering (AREA)
  • Physics & Mathematics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Fluid Mechanics (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Emergency Medicine (AREA)
  • Vascular Medicine (AREA)
  • Anesthesiology (AREA)
  • Biomedical Technology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Molecular Biology (AREA)
  • Urology & Nephrology (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)
  • Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Check Valves (AREA)
  • Multiple-Way Valves (AREA)
  • Sampling And Sample Adjustment (AREA)
  • External Artificial Organs (AREA)
  • Separation Using Semi-Permeable Membranes (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
US10/114,765 2001-04-03 2002-04-03 Microfluidic device for concentrating particles in a concentrating solution Abandoned US20020172622A1 (en)

Priority Applications (2)

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US10/114,765 US20020172622A1 (en) 2001-04-03 2002-04-03 Microfluidic device for concentrating particles in a concentrating solution
US11/122,139 US20050201903A1 (en) 2001-04-03 2005-05-04 Microfluidic device for concentrating particles in a concentrating solution

Applications Claiming Priority (2)

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US28111401P 2001-04-03 2001-04-03
US10/114,765 US20020172622A1 (en) 2001-04-03 2002-04-03 Microfluidic device for concentrating particles in a concentrating solution

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US10/115,320 Abandoned US20020160518A1 (en) 2001-04-03 2002-04-03 Microfluidic sedimentation
US10/115,374 Abandoned US20020159920A1 (en) 2001-04-03 2002-04-03 Multiple redundant microfluidic structures cross reference to related applications
US10/114,790 Expired - Lifetime US6674525B2 (en) 2001-04-03 2002-04-03 Split focusing cytometer
US10/114,890 Abandoned US20020148992A1 (en) 2001-04-03 2002-04-03 Pneumatic valve interface for use in microfluidic structures
US10/114,864 Abandoned US20020150502A1 (en) 2001-04-03 2002-04-03 Surface tension reduction channel
US10/960,890 Abandoned US20050205816A1 (en) 2001-04-03 2004-10-06 Pneumatic valve interface for use in microfluidic structures
US11/122,139 Abandoned US20050201903A1 (en) 2001-04-03 2005-05-04 Microfluidic device for concentrating particles in a concentrating solution

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US10/115,374 Abandoned US20020159920A1 (en) 2001-04-03 2002-04-03 Multiple redundant microfluidic structures cross reference to related applications
US10/114,790 Expired - Lifetime US6674525B2 (en) 2001-04-03 2002-04-03 Split focusing cytometer
US10/114,890 Abandoned US20020148992A1 (en) 2001-04-03 2002-04-03 Pneumatic valve interface for use in microfluidic structures
US10/114,864 Abandoned US20020150502A1 (en) 2001-04-03 2002-04-03 Surface tension reduction channel
US10/960,890 Abandoned US20050205816A1 (en) 2001-04-03 2004-10-06 Pneumatic valve interface for use in microfluidic structures
US11/122,139 Abandoned US20050201903A1 (en) 2001-04-03 2005-05-04 Microfluidic device for concentrating particles in a concentrating solution

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US20020160518A1 (en) 2002-10-31
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US20020149766A1 (en) 2002-10-17
US20020159920A1 (en) 2002-10-31

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