Three dimensional microfluidic multiplexed diagnostic system

• US 10,080,526 B2
• Filed: 07/13/2012
• Issued: 09/25/2018
• Est. Priority Date: 07/13/2011
• Status: Active Grant

• Current Assignee: Leidos Innovations Technology, Inc.
• Original Assignee: Leidos Innovations Technology, Inc.
• Inventors: Palena, Patricia D., Jafri, Madiha, Poleski, Jason, Arnold, Sanipa K.
• Primary Examiner(s): Weston, Tiffany
• Assistant Examiner(s): TRAN, THO Q
• Application Number:
  US13/549,198
• Publication Number:
  US 20130018243A1
• Time in Patent Office: 2,265 Days
• CPC Class Codes: A61B 2560/0285 Apparatus for single use
• CPC Class Codes: A61B 2560/0443 Modular apparatus
• CPC Class Codes: A61B 2560/045 with a separable interface unit, e.g. for communication
• CPC Class Codes: A61B 2562/028 Microscale sensors, e.g. electromechanical sensors [MEMS]
• CPC Class Codes: A61B 2562/0285 Nanoscale sensors
• CPC Class Codes: A61B 2562/046 in a matrix array
• CPC Class Codes: A61B 5/0538 invasively, e.g. using a catheter
• CPC Class Codes: A61B 5/14735 comprising an immobilised reagent
• CPC Class Codes: A61B 5/6847 mounted on an invasive device
• CPC Class Codes: A61B 5/6865 Access ports
• CPC Class Codes: B01L 2300/0663 Whole sensors
• CPC Class Codes: B01L 2300/0681 Filter
• CPC Class Codes: B01L 2300/0819 Microarrays; Biochips
• CPC Class Codes: B01L 2300/0874 Three dimensional network
• CPC Class Codes: B01L 2300/0887 Laminated structure
• CPC Class Codes: B01L 2400/0406 capillary forces
• CPC Class Codes: B01L 2400/0424 Dielectrophoretic forces
• 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: B82Y 10/00 Nanotechnology for information processing, storage or transmission, e.g. quantum computing or single electron logic
• CPC Class Codes: B82Y 15/00 Nanotechnology for interacting, sensing or actuating, e.g. quantum dots as markers in protein assays or molecular motors
• CPC Class Codes: H10K 85/225 : comprising substituents

Abstract

A biosensor includes a microfluidics layer, a transduction layer and a transceiver layer. The transduction layer further includes a functionalized layer that reacts with a biomarker, and a plurality of carbon nanotubes adjacent the functionalized layer. The conductivity of the carbon nanotubes changes in response to a biomarker reacting with at least a portion of the functionalized layer. The functionalized layer can include dendrimers, such as a tadpole dendrimer scaffolding that includes a plurality of sites for receiving receptors for biomarkers.

Claims

1. A biosensor adapted for implantation comprising:

a microfluidics layer including

microfluidic filtration tunnels configured to filter a fluid sample using dielectrophoresis,

a matrix of micro-mechanical-electronic systems (MEMS) configured to open and close input and output portals at predetermined times, and

microfluidic capillaries positioned between the microfluidic filtration tunnels and the matrix of MEMS, wherein the microfluidic capillaries are configured to draw in the filtered fluid sample from the microfluidic filtration tunnels, wherein the filtered fluid sample is drawn in perpendicular to a direction of fluid flow through the microfluidic filtration tunnels;

a transceiver layer; and

a transduction layer positioned between the microfluidics layer and the transceiver layer and interfaced to the microfluidics layer via the output portals, wherein the transduction layer is configured to detect a biomarker of the filtered fluid sample, the transduction layer comprising;

a functionalized layer that reacts with the biomarker of the filtered fluid sample;

a plurality of carbon nanotubes adjacent the functionalized layer, the conductivity of the plurality of carbon nanotubes changing in response to a biomarker reacting with at least a portion of the functionalized layer.

2. The biosensor adapted for implantation of claim 1 wherein the functionalized layer includes dendrimers.

3. The biosensor adapted for implantation of claim 1 wherein the functionalized layer includes a tadpole dendrimer scaffolding for receiving receptors of biomarkers.

4. The biosensor adapted for implantation of claim 1 wherein the functionalized layer includes a plurality of one time use test locations.

5. The biosensor adapted for implantation of claim 1 further including a conductivity monitor which monitors conductivity of the functionalized layer and the plurality of carbon nanotubes for changes in conductivity.

6. The biosensor adapted for implantation of claim 5 wherein the conductivity monitor is communicatively coupled to the transceiver layer.

7. The biosensor adapted for implantation of claim 1 wherein the microfluidics layer includes a plurality of capillary tubes through which fluid samples flow.

8. The biosensor adapted for implantation of claim 1 wherein the microfluidics layer includes:

a plurality of capillary tubes through which fluid samples flow;

a plurality of input portals in fluid communication with the plurality of capillary tubes through which fluid samples flow; and

a plurality of output portals in fluid communication with a plurality of capillary tubes, the output portals placing fluid samples on portions of the functionalized layer of the transduction layer.

9. The biosensor adapted for implantation of claim 8 wherein the opening and closing of the input portals is controllable by a processor in the transceiver layer.

10. The biosensor adapted for implantation of claim 1 wherein the transceiver layer includes a processor for controlling portions of the microfluidics layer and monitoring the conductivity of portions of the transduction layer and for controlling communications with the biosensor.

11. A biosensor, for sensing a biomarker, adapted for implantation comprising:

a microfluidics layer including

microfluidic filtration tunnels configured to filter a fluid sample using dielectrophoresis,

a matrix of micro-mechanical-electronic systems (MEMS) configured to open and close input and output portals at predetermined times, and

microfluidic capillaries positioned between the microfluidic filtration tunnels and the matrix of MEMS, wherein the microfluidic capillaries are configured to draw in the filtered fluid sample from the microfluidic filtration tunnels, wherein the filtered fluid sample is drawn in perpendicular to a direction of fluid flow through the microfluidic filtration tunnels;

a transceiver layer comprising;

processing circuitry configured to

control the microfluidics layer, and

monitor the transduction layer for an indication that the predetermined biomarker is present; and

a communications device enabling communications between the biosensor and one or more external devices via a network; and

a transduction layer positioned between the microfluidics layer and the transceiver layer and interfaced to the microfluidics layer via the output portals, wherein the transduction layer is configured to detect a biomarker of the filtered fluid sample, the transduction layer comprising;

a functionalized layer that reacts with the biomarker of the filtered fluid sample; and

a plurality of carbon nanotubes adjacent the functionalized layer, the conductivity of the plurality of carbon nanotubes changing in response to a biomarker reacting with at least a portion of the functionalized layer.

12. The biosensor adapted for implantation of claim 11 wherein the transduction layer further comprises:

a functionalized layer that reacts with the predetermined biomarker; and

a plurality of carbon nanotubes adjacent the functionalized layer, the conductivity of the plurality of carbon nanotubes changing in response to the predetermined biomarker reacting with at least a portion of the functionalized layer, the plurality of carbon nanotubes acting as a field-effect biosensor.

13. The biosensor adapted for implantation of claim 12 wherein the functionalized layer includes a layer of dendrimers that includes receptor sites for the predetermined biomarkers.

14. The biosensor adapted for implantation of claim 12 further including a conductivity monitor which monitors conductivity of the functionalized layer and the plurality of carbon nanotubes for changes in conductivity and sends an indication of change in conductivity to the processor in the transceiver layer.

15. The biosensor adapted for implantation of claim 12 wherein the microfluidics layer includes a plurality of capillary tubes through which fluid samples flow, the fluid flow in at least one of the capillary tubes controlled by the processor in the transceiver layer.

16. The biosensor adapted for implantation of claim 11 wherein the microfluidics layer includes:

a plurality of capillary tubes through which fluid samples flow;

a plurality of input portals in fluid communication with a plurality of capillary tubes through which fluid samples flow; and

a plurality of output portals in fluid communication with a plurality of capillary tubes, the output portals placing fluid samples on portions of the functionalized layer of the transduction layer, at least one of the capillary tubes having an input portal and an output portal controllable by the processor of the transceiver layer.

17. The biosensor adapted for implantation of claim 11 wherein the processor includes an instruction set executable by the processor, the instructions for

controlling the fluid flow in the microfluidics layer;

monitoring the transduction layer for an indication of presence of a predetermined biomarker; and

communicating the indication of the predetermined biomarker from the biosensor to another device.

18. A method comprising:

implanting a biosensor in a body, the biosensor including a microfluidics layer, the microfluidics layer including

microfluidic filtration tunnels configured to filter a fluid sample using dielectrophoresis,

a matrix of micro-mechanical-electronic systems (MEMS) configured to open and close input and output portals at predetermined times, and

microfluidic capillaries positioned between the microfluidic filtration tunnels and the matrix of MEMS, wherein the microfluidic capillaries are configured to draw in the filtered fluid sample from the microfluidic filtration tunnels, wherein the filtered fluid sample is drawn in perpendicular to a direction of fluid flow through the microfluidic filtration tunnels;

delivering the fluid to a test site within the biosensor, wherein the test site includes a transduction layer positioned above between the microfluidics layer and a transceiver layer and interfaced to the microfluidics layer via the output portals, wherein the transduction layer is configured to detect a biomarker of the filtered fluid sample;

monitoring the test site within the biosensor for an indication that the predetermined biomarker is present in the fluid; and

communicating the indication to a device other than the biosensor.