Reusable thin film particle sensor
A microfluidic sensor formed by stacking a plurality of substantially non-electrically conductive layers, typically formed from thin polymer films. Certain layers may 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 certain embodiments of the sensor. Sensors generally include portions of a fluid path disposed parallel to the layers. Sensors may operate under the Coulter principle, and/or Stokes' shift phenomena. In certain embodiments, the sensor may be carried by a cartridge, which is adapted to couple with an interrogation platform. In any case, coupling desirably places the sensor in-circuit with operable interrogation structure, as well as with a fluid-flow control device. Structure included in a cartridge may provide fluid sample loading, routing, and storage capabilities.
1. A microfluidic sensor, comprising:
a plurality of stacked thin film substantially planar layers forming a cassette providing structure defining a fluid path disposed inside said sensor, said path comprising:
a first portion disposed parallel to, and within, said layers;
a second portion provided by a tunnel passing through an interrogation 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; and
a waste reservoir associated with said fluid path and structured to receive a plurality of individual and serially interrogated fluid samples.
2. The sensor according to claim 1 , wherein:
said waste reservoir is associated with an interrogation device.
3. The sensor according to claim 1 , wherein:
said cassette is structured for insertion into an interrogation device at a first optical interrogation orientation to permit running a first test, then to permit withdrawal and rotation of said cassette to a second optical interrogation orientation that is different from said first orientation for reinsertion of said cassette to permit running a second test.
4. The sensor according to claim 1 , wherein:
certain of said layers carry one or more electrode to dispose a plurality of electrodes in a 3-dimensional array in space; and
said cassette is structured for insertion into an interrogation device at a first electrical connection orientation to permit running a first test, then to permit withdrawal and rotation of said cassette to a second electrical connection orientation that is different from said first orientation for reinsertion of said cassette to permit running a second test.
5. The sensor according to claim 1 , further comprising:
means to detect a level of fluid in said reservoir.
6. The sensor according to claim 5 , wherein:
said waste reservoir is carried by said sensor.
7. The sensor according to claim 1 , further comprising:
alignment hole structure disposed relative to said second portion effective to facilitate precision orienting said second portion of an optically-based testing cassette when said alignment hole structure is installed in registration with alignment pin structure of a cooperatingly structured interrogation device.
8. The sensor according to claim 7 , wherein:
said alignment hole structure comprises:
a first aperture structured to define an X-Y position of a cassette at an installed position in, and with respect to, a cooperatingly structured interrogation device; and
a second aperture structured to interact with cooperating structure of said interrogation device to enforce substantially only a rotational aspect of said cassette with respect to said X-Y position.
9. The sensor according to claim 1 , wherein:
certain of said layers carry one or more electrode to dispose a plurality of electrodes in a 3-dimensional array in space; said electrodes 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;
a first interrogation electrode disposed for contact with fluid between said first stimulated electrode and said second stimulated electrode; and
a first trigger electrode arrangement operable to indicate a stop signal based upon detection of a fluid boundary, said first trigger electrode arrangement comprising a dedicated electrode disposed upstream of said second portion.
10. The sensor according to claim 9 , further comprising:
a second trigger electrode arrangement operable to indicate a start signal based upon detection of a fluid boundary, said second trigger electrode arrangement comprising a dedicated electrode disposed downstream of said second portion and spaced apart from said first trigger electrode arrangement by a length of lumen defining a known volume.
11. The sensor according to claim 9 , further comprising:
a second trigger electrode arrangement operable to indicate a start signal based upon detection of a fluid boundary, said second trigger electrode arrangement comprising a dedicated electrode disposed downstream of said second portion; and
a third trigger electrode arrangement operable to indicate a stop signal based upon detection of a fluid boundary, said third trigger electrode arrangement comprising a dedicated electrode disposed downstream of said second portion and spaced apart from said second trigger electrode arrangement by a length of lumen defining a known volume.
12. A method for manufacturing a multi-layer microfluidic sensor structured according to claim 1 , comprising:
forming a first fluid-flow channel in a first layer of thin film, said first fluid-flow channel being configured to permit fluid flow in a direction generally parallel to said first layer;
forming a second fluid-flow channel passing through a second layer of thin film to create an interrogation layer, said second fluid-flow channel being sized to urge single-file travel therethrough of particles entrained in a carrier fluid;
forming a third fluid-flow channel in a third layer of thin film, said third fluid-flow channel being configured to permit fluid flow in a direction generally parallel to said third layer, said first, second, and third fluid-flow channel being configured as individual portions of a first lumen extending through said sensor;
forming a plurality of alignment holes in penetration through said interrogation layer and disposed with sufficient precision relative to said second fluid-flow channel such that installation of two of said alignment holes in registration with respective locating pins of a cooperatingly structured interrogation device is effective to dispose said second fluid-flow channel at an interrogation location of said interrogation device within an accuracy of about 50 μm.
13. The method according to claim 12 , further comprising:
forming a fourth fluid-flow channel in said first layer of thin film, said fourth fluid-flow channel being configured to permit fluid flow in a direction generally parallel to said first layer;
forming a fifth fluid-flow channel passing through said second layer of thin film, said fifth fluid-flow channel being sized to urge single-file travel therethrough of particles entrained in a carrier fluid;
forming a sixth fluid-flow channel in said third layer of thin film, said sixth fluid-flow channel being configured to permit fluid flow in a direction generally parallel to said third layer, said forth, fifth, and sixth fluid-flow channel being configured as individual portions of a second lumen extending through said sensor;
forming a plurality of alignment holes in penetration through said interrogation layer and disposed with sufficient precision relative to said fifth fluid-flow channel such that installation of two of said alignment holes in registration with respective locating pins of a cooperatingly structured interrogation device is effective to dispose said fifth fluid-flow channel at an interrogation location of said interrogation device within an accuracy of about 50 μm.
14. The method according to claim 13 , wherein:
said cassette is structured to interface, at a first orientation, with said interrogation device to permit interrogation of a first fluid sample; and
said cassette is structured to interface, at a second orientation, with said interrogation device to permit interrogation of a second fluid sample.
15. The method according to claim 13 , wherein:
said first orientation is 180 degrees rotated from said second orientation.
16. The method according to claim 13 , wherein:
alignment holes formed in penetration through said first layer and said third layer are over-size, compared to alignment holes formed in penetration through said interrogation layer, to resist contact between material of said first layer and said third layer and said locating pins.
17. A method for interrogating particles entrained in a carrier fluid, comprising:
a) providing a microfluidic test cassette comprising:
a plurality of stacked thin film substantially planar layers forming a cassette providing structure defining a fluid path disposed inside said sensor, said path comprising:
a first portion disposed parallel to, and within, said layers;
a second portion provided by a tunnel passing through an interrogation 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;
b) loading a first fluid sample into said cassette;
c) installing said cassette in operable registration, at a first orientation, with an interrogation device;
d) urging flow of said first fluid sample through said cassette while using said interrogation device to interrogate a portion of said first sample;
e) removing said cassette from said interrogation device;
f) loading a second fluid sample into said cassette;
g) re-installing said cassette in operable registration, at a second orientation, with said interrogation device; and
h) urging flow of said second fluid sample through said cassette while using said interrogation device to interrogate a portion of said second sample.
18. A method for interrogating particles entrained in a carrier fluid, comprising:
a) providing a microfluidic test cassette comprising:
a plurality of stacked thin film substantially planar layers forming a cassette providing structure defining a fluid path disposed inside said sensor, said path comprising:
a first portion disposed parallel to, and within, said layers;
a second portion provided by a tunnel passing through an interrogation 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;
certain of said layers carrying one or more electrode to dispose a plurality of electrodes in a 3-dimensional array in space; said electrodes 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;
b) interrogating a plurality of fluid samples in series; and
c) electrically monitoring a health-indicating parameter of said cassette between at least two of said samples.
19. The method according to claim 18 , further comprising:
flushing said fluid path with a cleaning fluid during an interval between the interrogation of at least two of said fluid samples.
20. The method according to claim 18 , further comprising:
accumulating said fluid samples inside a container carried by said cassette.