Thin film particle sensor

• US 20090272179A1
• Filed: 03/10/2009
• Published: 11/05/2009
• Est. Priority Date: 05/05/2006
• Status: Active Grant

• Current Assignee: Orflo Technologies, LLC
• Original Assignee: E.I Spectra, LLC dba ORFLO Technologies (Gemini Bioproducts LLC)
• Inventors: Ayliffe, Harold E.
• Granted Patent: US 8,171,778 B2
• Time in Patent Office: Days
• US Class Current: 73/61.710
• CPC Class Codes: G01N 15/1023 Microstructural devices for non-optical measurement
• CPC Class Codes: G01N 15/12 by observing changes in resistance or impedance across apertures when traversed by individual particles, e.g. by using the Coulter principle
• CPC Class Codes: G01N 2015/1019 Associating Coulter-counter and optical flow cytometer [OFC]
• CPC Class Codes: G01N 2015/1024 Counting particles by non-optical means
• CPC Class Codes: G01N 2015/1029 Particle size

Abstract

A Coulter-style, microfluidic sensor formed by stacking a plurality of substantially non-electrically conductive layers, typically formed from thin polymer films. Certain layers carry patterned electrodes that are arranged to permit their connection to an electrical interrogation circuit. Electrodes may be disposed in a 3-dimensional array in the sensor. A fluid path through the sensor includes an orifice sized to promote single-file travel of particles. The orifice may be defined by a tunnel passing through at least one layer. Particles entrained in an electrolytic carrier fluid may be detected, or otherwise characterized, by interrogation circuitry connected to the sensor. Certain sensors may include portions of a fluid path disposed parallel to the layers. In certain preferred embodiments, the sensor is carried by a cartridge, which is adapted to couple with an interrogation platform. Desirably, such coupling places the sensor in-circuit with operable interrogation electronics, as well as with a fluid-flow control device. Structure included in a cartridge may provide fluid sample loading, routing, and storage capabilities.

Claims

1. A microfluidic sensor, comprising:

a plurality of stacked thin film substantially planar layers, certain of said layers carrying one or more electrode to dispose a plurality of electrodes in a 3-dimensional array in space; and

a fluid path, disposed inside said sensor, comprising;

a first portion disposed parallel to, and within, said layers;

a second portion provided by a tunnel passing through at least one layer, a constriction in said tunnel being sized to urge particles entrained in a carrier fluid into substantially single-file travel through a particle interrogation zone; and

a third portion disposed parallel to, and within, said layers, said first portion and said third portion being disposed on opposite sides of said particle interrogation zone.

2. The sensor according to claim 1, wherein:

an interrogation layer of said sensor comprises said at least one layer; and

at least one electrode is carried on each of top and bottom surfaces of said interrogation layer.

3. The sensor according to claim 2, further comprising:

a plurality of electrical surface connectors individually disposed in electrical communication with selected ones of each of said electrodes;

wherein;

all of said electrical surface connectors are disposed on a single side of said interrogation layer.

4. The sensor according to claim 1, further comprising:

a first trigger and a second trigger operable to indicate respective start and stop signals based upon detection of a fluid boundary, said first trigger and said second trigger having respective locations of effective operation that are disposed spaced apart by a lumen defining a known volume.

5. The sensor according to claim 4, wherein:

said first trigger comprises;

a first electrode disposed to contact fluid flowing through said sensor; and

a second electrode disposed to contact fluid flowing through said sensor, wherein;

said first trigger is structured to permit detecting impedance between said first electrode and said second electrode.

6. The sensor according to claim 5, wherein:

said second trigger comprises;

said first electrode; and

a third electrode disposed to contact fluid flowing through said sensor, wherein;

said second trigger is structured to permit detecting impedance between said first electrode and said third electrode.

7. The sensor according to claim 1, further comprising:

a first stimulated electrode disposed for contact with fluid in said first portion;

a second stimulated electrode disposed for contact with fluid in said third portion; and

a first interrogation electrode disposed for contact with fluid between said first stimulated electrode and said second stimulated electrode.

8. The sensor according to claim 7, wherein:

said first stimulated electrode and said second stimulated electrode each have a surface area, disposed for contact with fluid in said fluid path, greater than about 1/10 cm².

9. The sensor according to claim 7, further comprising:

a second interrogation electrode disposed between said first stimulated electrode and said second stimulated electrode.

10. The sensor according to claim 7, wherein:

the entire length of said first interrogation electrode, measured along an axis of said first portion, is disposed upstream of said tunnel.

11. The sensor according to claim 9, wherein:

the entire length of said second interrogation electrode, measured along an axis of said third portion, is disposed downstream of said tunnel.

12. The sensor according to claim 7, wherein:

a second interrogation electrode is disposed between said first stimulated electrode and said second stimulated electrode.

the entire length of said first interrogation electrode, measured along an axis of said first portion, is disposed upstream of said tunnel; and

the entire length of said second interrogation electrode, measured along an axis of said third portion, is disposed downstream of said tunnel.

13. The sensor according to claim 7, wherein:

the entire length of said first interrogation electrode, measured along an axis of said third portion, is disposed downstream of said tunnel.

14. The sensor according to claim 1, further comprising:

a particle filter disposed upstream of said interrogation zone, said particle filter consisting essentially of openings having a characteristic size that is smaller than a characteristic size of a minimum cross-section of said interrogation zone.

15. The sensor according to claim 1, further comprising:

flow termination structure disposed downstream from said interrogation zone, said flow termination structure being arranged to resist flow of fluid beyond a boundary associated with said microfluidic sensor.

16. The sensor according to claim 1, further comprising:

holding structure adapted to receive a quantity of sample fluid effective to define a volumetric size of a processed sample, said holding structure comprising a dead-end chamber defining, in harmony with trigger structure of said sensor, a known volume and being vented through a fluid barrier effective to resist further flow of fluid through said sensor subsequent to filling of said chamber.

17. A multi-layer microfluidic sensor, comprising:

a first fluid-flow channel formed in a first layer, said first fluid-flow channel being configured to permit fluid flow in a direction generally parallel to said first layer;

a first electrode disposed for contact with fluid in said first fluid-flow channel;

a second electrode disposed downstream of said first electrode, said first electrode and said second electrode being carried on a first side of an interrogation layer;

a second fluid-flow channel passing through said interrogation layer, said second fluid-flow channel being sized to urge single-file travel therethrough of particles entrained in a carrier fluid; and

a third electrode, disposed for contact with fluid in a third fluid-flow channel and carried on a second side of said interrogation layer, said third fluid-flow channel being formed in a layer and configured to permit flow of fluid received from said second fluid-flow channel to continue in a direction generally parallel to a layer.

18. The sensor according to claim 17, further comprising:

flow detection structure arranged to permit estimation of rate-of-flow of sample fluid downstream from said interrogation zone.

19. The sensor according to claim 17, further comprising:

an entrance port communicating to said first fluid-flow channel; and

an exit port communicating from said third fluid-flow channel, said entrance port and said exit port being disposed on the same side of said sensor.

20. The sensor according to claim 17, further comprising:

a first trigger and a second trigger operable to indicate respective start and stop signals based upon detection of a fluid boundary, said first trigger and said second trigger having respective locations of effective operation that are disposed spaced apart by a lumen defining a known volume.