Methods and apparatus for processing a sample of biomolecular analyte using a microfabricated device

• US 20010020588A1
• Filed: 01/23/2001
• Published: 09/13/2001
• Est. Priority Date: 09/15/1997
• Status: Active Grant

• Current Assignee: Whitehead Institute for Biomedical Research
• Original Assignee: Whitehead Institute for Biomedical Research
• Inventors: Adourian, Aram S., Schmalzing, Dieter R., Matsudaira, Paul T., Ehrlich, Daniel J., Koutny, Lance B.
• Granted Patent: US 6,991,713 B2
• Time in Patent Office: Days
• US Class Current: 204/451
• CPC Class Codes: B01L 2200/027 for microfluidic devices
• CPC Class Codes: B01L 2200/0605 Metering of fluids
• CPC Class Codes: B01L 2200/0647 Handling flowable solids, e.g. microscopic beads, cells, particles
• CPC Class Codes: B01L 2200/0657 Pipetting powder
• CPC Class Codes: B01L 2300/0803 Disc shape
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2400/0415 electrical forces, e.g. electrokinetic
• CPC Class Codes: B01L 2400/0421 electrophoretic flow
• CPC Class Codes: B01L 2400/043 magnetic forces
• CPC Class Codes: B01L 2400/0442 thermal energy, e.g. vaporisation, bubble jet
• CPC Class Codes: B01L 3/0275 Interchangeable or disposable dispensing tips
• CPC Class Codes: B01L 3/0289 Apparatus for withdrawing or distributing predetermined quantities of fluid B01L3/02 takes precedence; sample taking G01N1/00; sample taking within automatic analysers G01N35/00; volume measuring in general G01F
• CPC Class Codes: B01L 3/5025 for parallel transport of multiple samples
• CPC Class Codes: B01L 3/5027 by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip B01L3/5023 takes precedence; micromixers B01F33/30; microreactors for synthesis B01J19/0093; microcapillary devices in general B81B1/00
• CPC Class Codes: B01L 3/502715 characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• CPC Class Codes: B01L 3/502753 characterised by bulk separation arrangements on lab-on-a-chip devices, e.g. for filtration or centrifugation separation in general B01D; microapparatus for analysis using electrophoresis G01N27/44791; sample preparation G01N1/28
• CPC Class Codes: G01N 27/44743 Introducing samples
• CPC Class Codes: G01N 27/44782 of a plurality of samples
• CPC Class Codes: G01N 35/10 Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices G01N35/0099 takes precedence
• CPC Class Codes: Y10T 436/2575 Volumetric liquid transfer

Abstract

A technique processes a sample of biomolecular analyte. The technique uses an apparatus having a support assembly that receives and supports a test module, a load assembly that loads the sample of biomolecular analyte onto the test module, an electrophoresis assembly that applies a current to the test module such that components within the sample separate by electrophoresis, and a controller that controls operations of the load assembly and the electrophoresis assembly. The load assembly and the electrophoresis assembly are coupled to the support assembly. The controller controls the operation of the load assembly in an automated manner. Preferably, the test module includes a dielectric plate member having an upper planar surface and a lower planar surface that is spaced apart from and coplanar with the upper planar surface. The dielectric plate member has at least one set of channels that includes an injection channel and a separation channel. The injection channel extends from the upper planar surface to the lower planar surface. The separation channel extends within the dielectric plate member in a plane parallel with the upper and lower planar surfaces and intersects the injection channel.

Claims

1. A method for loading a test plate with a sample of biomolecular analyte that is disposed about a bead that is magnetically attractable, the method comprising the steps of:

activating an electromagnetic loading device to electromagnetically attract and carry the bead;

positioning the electromagnetic loading device adjacent an opening of the test plate; and

deactivating the electromagnetic loading device to release the bead at the opening of the test plate such that the sample of biomolecular analyte is loaded on the test plate.

2. The method of

claim 1

further comprising the step of:

activating an electromagnetic unloading device that provides a force on the bead in a direction away from the electromagnetic loading device and toward the opening of the test plate.

3. The method of

claim 1

wherein the step of positioning the electromagnetic loading device includes the step of:

actuating a robotic assembly that supports the electromagnetic loading device such that the electromagnetic loading device moves to a programmed position relative to the test plate.

4. A method for loading a test plate with a sample of biomolecular analyte that is disposed within a solution, comprising the steps of:

positioning a capillary adjacent an opening of the test plate;

activating an electrokinetics device coupled to a capillary such that the sample is drawn through the capillary onto the test plate using electrokinetics; and

deactivating the electrokinetics device such that the sample is no longer drawn through the capillary.

5. The method of

claim 4

wherein the step of activating includes the step of:

dispensing a fluid droplet of the sample onto the test plate.

6. A test module assembly, comprising:

a dielectric plate member having an upper planar surface and a lower planar surface that is spaced apart from and coplanar with the upper planar surface, the dielectric plate member having at least one set of channels that includes an injection channel and a separation channel, the injection channel extending from the upper planar surface to the lower planar surface, the separation channel extending within the dielectric plate member in a plane parallel with the upper and lower planar surfaces and intersecting the injection channel.

7. The test module assembly of

claim 6

wherein the injection channel intersects the separation channel at a right angle.

8. The test module assembly of

claim 7

wherein the injection channel terminates at the upper and lower planar surfaces at right angles to the upper and lower planar surfaces.

9. The test module assembly of

claim 6

wherein the injection channel terminates at the upper and lower planar surfaces at right angles to the upper and lower planar surfaces.

10. The test module assembly of

claim 6

wherein the dielectric plate member is wedge shaped.

11. The test module assembly of

claim 6

further comprising:

a housing that attaches to the dielectric plate member, the housing providing (i) a first opening over the upper planar surface such that a first end of the injection channel is accessible through the first opening, and (ii) a second opening over the lower planar surface such that a second end of the injection channel is accessible through the second opening.

12. The test module assembly of

claim 11

wherein the housing further provides a third opening over the upper planar surface such that the separation channel is accessible to a detection device through the third opening.

13. The test module assembly of

claim 11

further comprising:

a heating device, supported by the housing, that provides heat to the dielectric plate member when power is provided to the heating device.

14. The test module assembly of

claim 11

further comprising:

a first porous membrane that covers the first end of the injection channel and a second porous membrane that covers the second end of the injection channel to retain a matrix within the injection and separation channels, the first and second porous membranes being adhered to the dielectric plate member.

15. The test module assembly of

claim 11

further comprising:

an electromagnetic unloading device, coupled to the housing, that draws magnetic material towards the dielectric plate member when the electromagnetic unloading device is activated.

16. The test module assembly of

claim 6

wherein the dielectric plate member includes multiple sets of channels, each set of channels including an injection channel and a separation channel, the injection channel of each set extending from the upper planar surface to the lower planar surface, the separation channel of each set extending within the dielectric plate member in a plane parallel with the upper and lower planar surfaces and intersecting the injection channel of that set.

17. The test module assembly of

claim 16

wherein the injection channels of the multiple sets of channels are parallel with each other.

18. A method for separating a sample of biomolecular analyte, comprising the steps of:

drawing the sample along a longitudinal axis of an injection channel of a test plate using electrokinetics, the test plate being planar in shape along an orthogonal axis to the longitudinal axis; and

subsequently drawing the sample along the orthogonal axis through a separation channel of the test plate using electrokinetics, the separation channel intersecting the injection channel within the test plate.

19. The method of

claim 18

further comprising the steps of:

drawing multiple samples along the longitudinal axes of multiple other injection channels using electrokinetics simultaneously with the step of drawing the sample; and

drawing the multiple samples along other orthogonal axes through multiple other separation channels using electrokinetics, the multiple other separation channels respectively intersecting the multiple other injection channels.

20. The method of

claim 19

further comprising the step of:

scanning a respective portion of the separation channel and the multiple other separation channels with a detection device.

21. A test module assembly, comprising:

a rotatable dielectric plate member having an upper planar surface and a lower planar surface that is spaced apart from and coplanar with the upper planar surface, the rotatable dielectric plate member having multiple separation channels that extend within the rotatable dielectric plate member in a plane parallel with the upper and lower planar surfaces, the multiple separation channels extending radially from an inner portion of the rotatable dielectric plate member to an outer portion of the rotatable dielectric plate member.

22. The test module assembly of

claim 21

wherein the rotatable dielectric plate member is disk shaped and further includes multiple injection channels, each of the multiple injection channels intersecting a corresponding one of the multiple separation channels within the outer portion of the rotatable dielectric plate member.