ELECTROCHEMICAL DETECTION SYSTEM

• US 20080217246A1
• Filed: 03/10/2008
• Published: 09/11/2008
• Est. Priority Date: 03/09/2007
• Status: Active Grant

• Current Assignee: Vantix Holdings Limited
• Original Assignee: DxTech LLC
• Inventors: Carvalho, Bruce, Morris, Roger, Gover, Andy, Benn, Jim
• Granted Patent: US 8,506,908 B2
• Time in Patent Office: Days
• US Class Current: 210/645
• CPC Class Codes: B01L 2300/0645 Electrodes
• CPC Class Codes: B01L 2300/0672 Integrated piercing tool
• CPC Class Codes: B01L 2300/0681 Filter
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/123 Flexible; Elastomeric
• CPC Class Codes: B01L 2400/0481 squeezing of channels or chambers
• CPC Class Codes: G01N 2035/00148 Test cards, e.g. Biomerieux or McDonnel multiwell test cards
• CPC Class Codes: G01N 2035/00158 Elements containing microarrays, i.e. "biochip"
• CPC Class Codes: G01N 2035/00881 network configurations
• CPC Class Codes: G01N 35/00029 provided with flat sample substrates, e.g. slides G01N35/028 takes precedence

Abstract

An electrochemical detection system having a disposable cartridge capable of performing a plurality of assay protocols is disclosed. The cartridge includes a blister pack for the long-term storage and controlled release of multiple reagents. The blister pack is bonded to and operatively associated with a fluidic backbone for providing the fluid pathways, storage capacity, and fluid control functions for performing multiple assay protocols. The cartridge further includes a plurality of sensors having a multiple electrode arrangement in operative association with a respective flow cell defined by the fluidic backbone. After the user has transferred a sample into the cartridge and engaged the cartridge to the reader, the reader operatively interfaces with the cartridge such that different assay protocols may be simultaneously performed in isolation from one another inside the cartridge. The reader may be one of many readers that operatively communicate data to a remote server for processing.

Claims

1. A cartridge for performing a plurality of assay protocols comprising:

a blister pack including a plurality of blister domes for storing a respective reagent;

the blister pack having a deformable upper portion and a frangible lower portion for the controlled release of the respective reagent when a mechanical force is applied to one or more of the plurality of blister domes;

a fluidic backbone engaged to the blister pack, the fluidic backbone including a plurality of channels in selective fluid flow communication with a plurality of flow cells through an arrangement of valves such that each of the plurality of flow cells is isolated from the other flow cells during the performance of a plurality of assay protocols; and

a plurality of sensors operatively associated with a respective flow cell for detecting a reaction during the performance of a plurality of assays.

2. The cartridge of claim 1, further including a flexible adhesive film engaged between the blister pack and the fluidic backbone.

3. The cartridge of claim 2, wherein a sample reservoir is formed between the flexible adhesive film and the fluidic backbone.

4. The cartridge of claim 3, wherein the sample reservoir deforms the flexible adhesive film when a liquid fills the space between the fluidic backbone and the flexible adhesive film.

5. The cartridge of claim 1, wherein the cartridge is adapted to operatively engage a reader capable of mechanically actuating the cartridge from only one side of the cartridge.

6. The cartridge of claim 5, wherein the reader mechanically actuates the cartridge using a plurality of pistons or rollers.

7. The cartridge of claim 1, wherein the arrangement of valves includes a plurality of valve sites defined by the blister pack that correspond to a plurality of valves in communication with a respective channel defined by the fluidic backbone for collectively preventing or permitting fluid flow through the respective channel, wherein each of the plurality of valves defines an inlet in selective fluid flow communication with an outlet through a well, wherein each of the plurality of valve sites includes a deformable material adapted to engage the valve to prevent fluid flow communication between the inlet and the outlet and disengage from the valve to permit fluid flow communication between the inlet and the outlet.

8. The cartridge of claim 7, wherein the cartridge is adapted to operatively engage a reader such that the reader mechanically actuates one or more of the plurality of valve sites to prevent or permit fluid flow communication by engaging or disengaging the one or more of the valve sites relative to a respective one of the plurality of valves.

9. The cartridge of claim 1, wherein the cartridge is adapted to operatively engage a reader such that the reader mechanically actuates one or more of the plurality of blister domes such that the deformable upper portion becomes deformed while the frangible lower portion breaks apart.

10. The cartridge of claim 9, wherein each of the plurality of blister domes contains a fluid, and each of the plurality of blister domes is in fluid flow communication with a puncture valve site that corresponds to a puncture site base for establishing fluid flow communication with a channel when the puncture site base is mechanically actuated by the reader.

11. The cartridge of claim 10, wherein fluid from the plurality of blister domes is released into the respective channel by mechanically actuating the puncture valve site to establish fluid flow communication with the respective channel, and then mechanically actuating the plurality of blister domes such that liquid is released from the plurality of blister domes and through a respective puncture valve site, wherein mechanical actuation of the plurality of blister domes and the puncture valve sites causes the deformable upper portion to become deformed and the frangible lower portion to break apart in order to establish fluid flow communication between the plurality of blister domes and one of the plurality of channels upon mechanical actuation by the reader.

12. The cartridge of claim 1, wherein each of the plurality of sensors includes an arrangement of four electrodes that are operatively associated with a respective one of the plurality of flow cells for detecting an electrochemical reaction.

13. The cartridge of claim 12, wherein the arrangement of four electrodes includes three working electrodes and a reference electrode.

14. The cartridge of claim 13, wherein at least one of the working electrodes is a working calibration electrode for providing a means of calibrating each of the plurality of sensors.

15. The cartridge of claim 1, further including a bottom lid that is engaged to the fluidic backbone for defining the plurality of channels.

16. The cartridge of claim 1, wherein the deformable upper portion and the frangible lower portion may define a respective finger channel in fluid flow communication between one of the plurality of blister domes and a respective puncture valve site, the fluid backbone defining a puncture site base corresponding to the puncture valve site with the puncture site base defining an outlet in fluid flow communication with a respective one of the plurality of flow cells.

17. The cartridge of claim 16, wherein the fluid flow is initiated by mechanically engaging the puncture valve site against the puncture site base to establish fluid flow communication between one of the plurality of blister domes and the puncture site base, and then mechanically actuating the one of the plurality of blister domes to permit the release of liquid through the outlet of the puncture site base.

18. The cartridge of claim 1, wherein a fluidic pathway is defined between the deformable upper portion and the frangible lower portion such that the mechanical actuation of the blister pack causes the deformable upper portion to deform and the frangible lower portion to break apart.

19. An electrochemical detection system comprising:

a reader capable of initiating and detecting a plurality of electrochemical reactions from the performance of a respective plurality of assay protocols,

a cartridge adapted to operatively engage the reader for initiating the performance of the plurality of assay protocols within the cartridge, the cartridge including a blister pack having a plurality of blister domes for storing a respective fluid, the blister pack having a deformable upper portion and a frangible lower portion for the controlled release of the respective reagent when a mechanical force is applied to at least one of the plurality of blister domes by the reader;

a fluidic backbone engaged to the blister pack, the fluidic backbone including a plurality of channels in selective fluid flow communication with a plurality of flow cells through an arrangement of valves, each of the plurality of flow cells being in selective fluid flow communication with one or more blister domes such that a plurality of assay protocols may be may be simultaneously performed when one or more of the respective reagents is released from at least one of the plurality of blister domes; and

a plurality of sensors with each of the plurality of sensors being in operative association with one of the plurality of flow cells for detecting a chemical reaction within each one of the plurality of flow cells.

20. The electrochemical detection system of claim 19, wherein the reader includes a plurality of mechanical actuators for mechanically actuating respective portions of the blister pack for initiating the controlled release of fluid stored from each of the plurality of blister domes.

21. The electrochemical detection system of claim 20, wherein the mechanical actuators include pistons or rollers.

22. The electrochemical detection system of claim 20, further including an adhesive film engaged between the fluidic backbone and the blister pack, wherein the fluidic backbone further includes an input port in selective fluid flow communication with a sample reservoir adapted to receive a liquid sample, wherein the adhesive film and the fluidic backbone collectively define the sample reservoir for storage of the liquid sample.

23. The electrochemical detection system of claim 22, wherein the reader mechanically actuates the cartridge by applying a mechanical force to the sample reservoir in order to positively displace the liquid sample sequentially through the plurality of flow cells.

24. The electrochemical detection system of claim 19, wherein the arrangement of valves isolates and prevents fluid flow communication between each of the plurality of flow cells, thereby allowing simultaneous performance of an assay protocol in each of the plurality of flow cells.

25. A method of manufacturing a sensor for use in electrochemical analysis comprising:

screen printing a plurality of conductive tracks on a non-conductive medium;

each of the plurality of conductive tracks having a distal end and a proximal end;

screen printing a plurality of working carbon electrodes that are each operatively engaged to the distal end of each one of the plurality of conductive tracks;

applying a dielectric layer on the non-conductive medium that covers the area outside of the working carbon electrodes; and

engaging a conductor at the proximal end of each one of the plurality of conductive tracks.

26. A method for extracting plasma from whole blood comprising:

providing a plasma separation component adapted to extract plasma from whole blood, wherein the plasma separation component includes a glass fiber filter arrangement defining an inlet and an outlet;

introducing a whole blood sample to the glass fiber filter through the inlet;

allowing the whole blood sample to wick through the glass fiber filter arrangement over a predetermined period of time such that red blood cells from the whole blood sample are retained by the glass fiber filter arrangement, thereby producing plasma;

introducing a working fluid into the inlet of the glass fiber filter after the predetermined period of time; and

extracting the plasma from the outlet of the glass fiber filter arrangement.

27. An electrochemical detection system comprising:

a cartridge having top and bottom side, wherein the cartridge includes a blister pack including a plurality of deformable blister domes and a sample reservoir for storing a respective fluid in selective fluid flow communication with a plurality of flow cells for performing a plurality of assay protocols, the blister pack having a deformable upper portion and a frangible lower portion that defines a fluid pathway between the upper portion and the lower portion adapted for fluid flow communication; and

a reader adapted to be operatively engaged to the cartridge for initiating performance of the plurality of assay protocols, the reader including a plurality of mechanical actuators for engaging a respective plurality of blister domes such that application of a respective one of the plurality of mechanical actuators to a respective one of the plurality of blister domes causes deformation of the upper portion while breaking apart the frangible lower portion of the blister pack such that stored fluid may be released to one of the plurality of flow cells, wherein mechanical actuation of the cartridge by the reader occurs only from the top or the bottom side of the cartridge.

28. A method of manufacturing a blister pack for a cartridge utilized to perform a plurality of assay protocols comprising:

providing a blister pack that defines a deformable upper portion and a frangible lower portion; and

applying a sealing process to certain areas of the blister pack that bonds together the upper portion to the lower portion such that areas not exposed to the sealing process defines a fluid pathway such that the application of a mechanical force to the fluid pathway will deform the deformable upper portion while breaking apart the frangible lower portion.

29. The method of claim 28, wherein the blister pack defines a blister dome having a chamber adapted to store and release a fluid that is in communication with a puncture valve site through a finger channel.

30. The method of claim 29, wherein the application of a mechanical force deforms the blister dome and positively displaces any fluid contained in the chamber.

31. The method of claim 28, wherein the blister pack defines a valve site adapted to engage and disengage a fluidic backbone that defines an outlet such that fluid flow communication is permitted or prevented.