Cartridge for MEMS particle sorting system

• US 20120190105A1
• Filed: 01/23/2012
• Published: 07/26/2012
• Est. Priority Date: 01/21/2011
• Status: Active Grant

• Current Assignee: Miltenyi Biotec, Incorporated (Miltenyi GmbH)
• Original Assignee: Innovative Micro Technology Incorporated, Owl Biomedical, Inc. (Miltenyi GmbH)
• Inventors: Foster, John S., Grummitt, Daryl W., Harley, John C., Spong, Jaquelin K., Linton, James P.
• Granted Patent: US 8,822,207 B2
• Time in Patent Office: Days
• US Class Current: 435/288.7
• CPC Class Codes: B01L 2200/0652 Sorting or classification of particles or molecules
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2400/043 magnetic forces
• CPC Class Codes: B01L 2400/0439 ultrasonic vibrations, vibrating piezo elements
• CPC Class Codes: B01L 2400/0478 pistons
• CPC Class Codes: B01L 2400/0481 squeezing of channels or chambers
• 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: B01L 7/52 with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples amplification or hybridisation processes per se C12Q1/68; controlling sequential reactions for synthesis B01J19/0046
• CPC Class Codes: C12M 47/04 Cell isolation or sorting purging biological preparations of unwanted cells C12N5/0081, determining the presence or kind of microorganism C12Q1/04
• CPC Class Codes: G01N 15/1459 the analysis being performed on a sample stream
• CPC Class Codes: G01N 15/149 specially adapted for sorting particles, e.g. by their size or optical properties

Abstract

A disposable cartridge is described which is compatible with a MEMS particle sorting device. The disposable cartridge may include passageways which connect fluid reservoirs in the cartridge with corresponding microfluidic passageways on the MEMS chip. A flexible gasket may prevent leakages and allow the fluid to cross the gasket barrier through a plurality of holes in the gasket. Vents and septums may also be included to allow air to escape and fluids to be inserted by hypodermic needle. A MEMS-based particle sorting system using the disposable cartridge is also described.

Claims

1. A substantially sealed, disposable cartridge for a MEMS particle sorting system, comprising:

at least one microfabricated particle sorting structure formed on a substrate and installed in the substantially sealed, disposable cartridge;

a quantity of biocompatible material with a plurality of fluid reservoirs disposed therein, with one or more fluidic passageways connecting the fluid reservoirs to the MEMS particle sorting system

a flexible gasket covering the reservoirs, wherein a plurality of holes formed in the gasket allows a fluid flow to between at least one of the reservoirs and the microfabricated particle sorting structure.

2. The substantially sealed, disposable cartridge of claim 1, further comprising:

a sample fluid disposed in a sample reservoir;

a sample input passageway upstream of the microfabricated particle sorting structure, a sort passageway and a waste passageway downstream of the microfabricated particle sorting structure, which are in fluid communication with the sample reservoir, the microfabricated particle sorting structure, a sort reservoir and a waste reservoir,

wherein the microfabricated particle sorting structure diverts a target particle from the sample passageway to the sort passageway and blocks the waste passageway when the target particle is detected, and

wherein the sort passageway, sort reservoir, waste passageway and waste reservoir are all formed in the substantially sealed, disposable cartridge.

3. The substantially sealed, disposable cartridge of claim 2, further comprising:

at least one vent formed in the biocompatible material which permits a gas to pass from at least one of the reservoirs to an environment external to the substantially sealed, disposable cartridge.

4. The substantially sealed, disposable cartridge of claim 2, further comprising:

a lid affixed to the gasket to seal the gasket against the quantity of biocompatible material and against the substrate, and wherein the gasket is disposed against the quantity of biocompatible material on one side of the gasket, and the lid and substrate on another side of the gasket.

5. The substantially sealed, disposable cartridge of claim 2, further comprising:

a flexible sample input septum associated with the sample reservoir; and

a magnetic stir bar disposed at the bottom of the sample reservoir.

6. The substantially sealed, disposable cartridge of claim 5, wherein the input septum is in fluid communication with the sample reservoir by a fluid channel linking the input septum with the sample reservoir.

7. The substantially sealed, disposable cartridge of claim 2, further comprising:

at least one transparent viewing window disposed at the bottom of at least one of the sort reservoir and the waste reservoir.

8. The substantially sealed, disposable cartridge of claim 2, further comprising:

a detection region in the input passageway, wherein as the sample fluid flows through the detection region, a signal is obtained from the sample fluid which distinguishes a target particle from the other components of the sample fluid, wherein this signal is based on at least one of an electrical attribute, a hydrodynamic attribute, a magnetic attribute, mass, an optical attribute, a thermal attribute, and a mechanical attribute of the particle.

9. The substantially sealed, disposable cartridge of claim 2, wherein:

the microfabricated particle sorting structure includes a movable structure which pivots around at least one fixed point, wherein each of the fixed points is located on the same side of an axis of motion of the movable structure, and wherein the movable structure opens a sort channel to divert the target particle into the sort channel when the movable structure pivots about the at least one fixed point.

10. The substantially sealed, disposable cartridge of claim 2, wherein the sample reservoir has a curved floor forming the bottom of the input reservoir;

and wherein the sort reservoir and waste reservoirs each have a substantially rectangular cross section with a flat floor.

11. The substantially sealed, disposable cartridge of claim 9, further comprising:

at least one transparent viewing window at the bottom of at least one of the sort reservoir and the waste reservoir, allowing the contents of at least one of the sort reservoir and the waste reservoir to be viewed from below the respective reservoirs.

12. A MEMS particle sorting system, comprising:

the substantially sealed, disposable cartridge of claim 1; and

a detector which detects a target particle passing in a sample fluid flowing through a detection region in the microfabricated particle sorting structure.

13. The MEMS particle sorting system of claim 12, further comprising:

a laser whose output is directed onto the detection region of the microfabricated particle sorting structure, wherein the laser light impinges orthogonally on the detection region and the sample fluid flowing therethrough.

14. The MEMS particle sorting system of claim 12, further comprising:

an optical axis oriented orthogonally to a plane of the substrate, the detection region and the flow therethrough;

at least one turning mirror which redirects the output of the laser onto the optical axis;

at least one optical detector; and

at least one dichroic mirror disposed on the optical axis which redirects fluorescent light from the detection region into the at least one optical detector.

15. The MEMS particle sorting system of claim 14, further comprising:

a force-generating apparatus which induces motion in the microfabricated particle sorting structure toward the force-generating apparatus, without being mechanically coupled to the microfabricated particle sorting structure.

16. The MEMS particle sorting system of claim 14, further comprising:

a controller which receives a signal from the at least one optical detector, and outputs a signal to the force-generating apparatus, activating the force-generating apparatus to move the microfabricated particle sorting structure.

17. The MEMS particle sorting system of claim 14 further comprising:

a piston which exerts a pressure on the flexible gasket, forcing a fluid to move from one of the fluid reservoirs to the microfabricated particle sorting structure, to another of the fluid reservoirs under the pressure from the piston.

18. The MEMS particle sorting system of claim 14, further comprising:

a vibration-generating mechanism which is mechanically coupled to at least one of the flexible gasket and the biocompatible material, that applies a transient pressure wave to the sample fluid in the fluidic passageways.

19. The MEMS particle sorting system of claim 14, further comprising:

at least one of refrigeration and heating apparatus which is thermally coupled to the disposable cartridge, that cools or heats the sample fluid in the disposable cartridge.

20. The MEMS particle sorting system of claim 14, further comprising:

a mechanism which generates a rotating magnetic field, which may interact with a magnetic stirrer in the substantially sealed, disposable cartridge, to mix the sample fluid.