Microfluidic channel embryo and/or oocyte handling, analysis and biological evaluation

• US 6,695,765 B1
• Filed: 05/12/2000
• Issued: 02/24/2004
• Est. Priority Date: 04/08/1999
• Status: Active Grant

• Current Assignee: Board of Trustees of The University of Illinois
• Original Assignee: Board of Trustees of The University of Illinois
• Inventors: Beebe, David J., Zeringue, Henry, Glasgow, Ian K., Wheeler, Matthew B.
• Primary Examiner(s): Shaver, Kevin
• Assistant Examiner(s): SZMAL, BRIAN SCOTT
• Application Number:
  US09/570,483
• Time in Patent Office: 1,383 Days
• Field of Search: 600/33, 600/35, 435/7.2
• US Class Current: 600/33
• CPC Class Codes: A61B 17/435 for embryo or ova transplantation
• CPC Class Codes: A61D 19/04 for embryo transplantation
• CPC Class Codes: B01L 2200/143 Quality control, feedback systems
• CPC Class Codes: B01L 2400/0457 passive flow or gravitation
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 2400/0688 surface tension valves, capillary stop, capillary break
• CPC Class Codes: B01L 2400/086 using baffles or other fixed flow obstructions
• CPC Class Codes: B01L 3/502707 characterised by the manufacture of the container or its components by shaping or joining plastic parts B29C59/00, B29C65/00; by laminating B32B37/00; manufacture of microstructural devices in general B81C
• CPC Class Codes: B01L 3/502761 specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads, for physically stretching molecules investigating characteristics of particles G01N15/00
• CPC Class Codes: C12M 21/06 for in vitro fertilization
• CPC Class Codes: C12M 23/16 Microfluidic devices; Capillary tubes integrated microfluidic structures B01L3/5027; microreactors B01J19/0093
• CPC Class Codes: C12M 29/10 Perfusion
• CPC Class Codes: C12M 41/00 Means for regulation, monitoring, measurement or control, e.g. flow regulation controlling or regulating chemical, physical or physicochemical processes B01J19/0006; heating or cooling apparatus for laboratory use B01L7/00; electro optical investigation of individual particles, flow cytometers G01N15/14; automatic analysis G01N35/00; controlling or regulating in general G06N

Abstract

Microfluidic embryo scaled channels for handling and positioning embryos provide the opportunity to evaluate and treat embryos in improved manners Fluid flow is used to move and position embryos within microfluidic channels and channel geometries may be used to place embryos at specific locations. Surface properties and compliance (deformation) properties of embryos are evaluated as a predictor of viability. The microfluidic channels provide the opportunity for fine controls of pressure to conduct various evaluations at forces slightly below which damage to embryos is known to occur.

Claims

1. A method for evaluating embryos, the method comprising steps of:

placing an embryo in an approximately embryo scaled fluid channel;

creating a fluid flow in the fluid channel; and

evaluating an embryo characteristic while an embryo is within the embryo scaled fluid channel.

2. The method according to claim 1, wherein said step of creating a fluid flow moves an embryo in the fluid channel, and said step of evaluating an embryo characteristic comprises measuring the speed at which an embryo moves in the fluid channel.

3. The method according to claim 1, wherein said step of creating a fluid flow moves an embryo in the fluid channel, and said step of evaluating an embryo characteristic comprises measuring the distance an embryo moves in the fluid channel.

4. The method according to claim 1, wherein said step of evaluating comprises obtaining a fluid sample from the fluid channel downstream of an embryo in the fluid channel and conducting a chemical analysis of the fluid sample.

5. The method according to claim 1, wherein the fluid channel includes a constriction sized to deform an embryo as it passes through and said step of evaluating evaluates a tendency of an embryo to return its shape after passing through the constriction.

6. The method according to claim 1, wherein the fluid channel includes a constriction sized to prevent passage of an embryo, said step of creating creates a fluid flow to move an embryo to the constriction and then deform it slightly by fluid pressure for a short period of time, and said step of evaluating evaluates a tendency of an embryo to return its shape after being deformed for the short period of time.

7. A method for treating embryos, the method comprising steps of:

placing an embryo in an approximately embryo scaled fluid channel;

creating a fluid flow in the fluid channel; and

treating an embryo to alter a characteristic of the embryo while it is positioned within the fluid channel.

8. The method according to claim 7, wherein said fluid channel includes a series of constrictions including protrusions having gradually less space therebetween, and said step of treating comprises manipulating the fluid flow in the fluid channel to pass an embryo through one or more of the constrictions and to remove cumulus.

9. The method according to claim 8, wherein a last one of the series of constrictions is sized to block passage of the embryo, and said step of treating comprises manipulating the fluid flow in the fluid channel to pass an embryo through other ones of the series of constrictions and then manipulating the fluid flow to suck off cumulus when an embryo is positioned at the last one of the series of constrictions.

10. The method according to claim 7, wherein the fluid channel includes a constriction sized to prevent passage of an embryo, said step of treating comprises altering the fluid in the fluid channel to pass an acidic solution over an embryo positioned at the constriction to remove zona pellucida.

11. A microfluidic embryo handling device comprising:

an embryo transport network having a biological medium for movement of embryos inserted therein, said transport network including an approximate embryo scaled embryo fluid channel and an opening for delivering fluid into the transport network; and

a t-junction in the transport formed at the intersection of two fluid channels, and a second opening for delivering fluid into the transport network at a separate fluid channel location.

12. The device according to claim 11, further comprising a well in said fluid channel formed to hold an embryo during periods predetermined flow rate within said fluid channel and allow escape of an embryo during periods of lower than said predetermined flow a rate within said fluid channel.

13. A microfluidic embryo fertilization device comprising:

an embryo transport network having a biological medium for movement of embryos inserted therein, said transport network including an approximate embryo scaled embryo fluid channel and an opening for delivering fluid into the transport network; and

a T-junction in the transport network formed at the intersection of two fluid channels, and a second opening for delivering sperm into the transport network at a separate fluid channel location.