Portable interstitial fluid monitoring system

• US 6,591,124 B2
• Filed: 05/11/2001
• Issued: 07/08/2003
• Est. Priority Date: 05/11/2001
• Status: Expired due to Term

• Current Assignee: Corium, Inc.
• Original Assignee: The Procter & Gamble Company
• Inventors: Arias, Francisco, Huang, Chow Chi, Gartstein, Vladimir, Sherman, Faiz Feisal, Owens, Grover David, Jevtitch, Milan Marcel
• Primary Examiner(s): Lazarus, Ira S.
• Assistant Examiner(s): NGUYEN, CAMTU TRAN
• Application Number:
  US09/853,442
• Publication Number:
  US 20020169411A1
• Time in Patent Office: 788 Days
• Field of Search: 604/27, 604/46, 604/19, 604/22, 604/20, 604/48, 600/576, 600/578, 600/38, 600/48, 600/573, 600/345, 600/365, 600/362, 600/309, 606/189, 606/186, 606/167
• US Class Current: 600/345
• CPC Class Codes: A61B 2560/04 Constructional details of apparatus
• CPC Class Codes: A61B 2562/0295 Strip shaped analyte sensors for apparatus classified in A61B5/145 or A61B5/157 disposable multilayered or laminated electrodes G01N27/307; details of handling chemical test elements G01N33/4875
• CPC Class Codes: A61B 5/14514 using means for aiding extraction of interstitial fluid, e.g. microneedles or suction
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/1455 using optical sensors, e.g. spectral photometrical oximeters
• CPC Class Codes: A61B 5/1486 using enzyme electrodes, e.g. with immobilised oxidase
• CPC Class Codes: A61B 5/150022 for capillary blood or interstitial fluid
• CPC Class Codes: A61B 5/150076 by heating
• CPC Class Codes: A61B 5/150099 by negative pressure, other than vacuum extraction into a syringe by pulling on the piston rod or into pre-evacuated tubes
• CPC Class Codes: A61B 5/150221 Valves
• CPC Class Codes: A61B 5/150229 Pumps for assisting the blood sampling
• CPC Class Codes: A61B 5/150358 Strips for collecting blood, e.g. absorbent optical reagent test strips G01N21/8483; chemical reagent test strips G01N33/4875, G01N33/52
• CPC Class Codes: A61B 5/150389 Hollow piercing elements, e.g. canulas, needles, for piercing the skin
• CPC Class Codes: A61B 5/150503 Single-ended needles hollow piercing element tip design A61B5/150396, needle sets for catheters A61M25/06, needles for bringing media into the body A61M5/32
• CPC Class Codes: A61B 5/150938 by blunting or disabling needle
• CPC Class Codes: A61B 5/150969 Low-profile devices which resemble patches or plasters, e.g. also allowing collection of blood samples for testing
• CPC Class Codes: A61B 5/150984 Microneedles or microblades
• CPC Class Codes: A61B 5/15105 Purely manual piercing, i.e. the user pierces the skin without the assistance of any driving means or driving devices
• CPC Class Codes: A61B 5/15113 Manually triggered, i.e. the triggering requires a deliberate action by the user such as pressing a drive button
• CPC Class Codes: A61B 5/15125 comprising a vacuum or compressed fluids
• CPC Class Codes: A61B 5/15142 : Devices intended for single use, i.e. disposable
• CPC Class Codes: A61B 5/15153 : Multiple piercing elements stocked in a single compartment
• CPC Class Codes: A61B 5/15163 : Characterized by propelling the piercing element in an axial direction relative to the disc
• CPC Class Codes: A61B 5/15169 : Characterized by a rolled strip
• CPC Class Codes: A61B 5/15171 : Characterized by propelling the piercing element perpendicular to the direction of movement of the strip
• CPC Class Codes: A61B 5/15178 : Stocking means comprising separate compartments or units for new and for used piercing elements separate compartments for used piercing elements in piercing devices A61B5/15184
• CPC Class Codes: A61B 5/15186 : Devices loaded with a single lancet, i.e. a single lancet with or without a casing is loaded into a reusable drive device and then discarded after use; drive devices reloadable for multiple use
• CPC Class Codes: A61B 5/155 : Devices specially adapted for continuous or multiple sampling, e.g. at predetermined intervals devices loaded with multiple lancets simultaneously A61B5/15146
• CPC Class Codes: A61B 5/157 : Devices characterised by integrated means for measuring characteristics of blood
• CPC Class Codes: A61M 2230/201 : Glucose concentration
• CPC Class Codes: A61M 37/0015 : by using microneedles

Abstract

A strip-like microneedle device is provided that includes an array of hollow microneedles, a diaphragm pump to extract interstitial fluid from skin, and a sensor that detects the concentration of the fluid. The microneedle device can be interfaced to an external sensor to produce a reading, or can be self-contained. One version uses an attachable/detachable microneedle array as a single-use, disposable unit. The device is portable, and is used by placing one finger on the microneedle array, and actuating the diaphragm pump with another finger, thereby obtaining the fluid sample. Solid coated or transparent microneedles could instead be used as an in-situ sensor, with either electrodes or an optical sensor.

Claims

1. A fluid sampling apparatus, comprising:

(a) a plurality of microneedles accessible on a first surface of said fluid sampling apparatus;

(b) a manually-operated pumping apparatus accessible on a second surface of said fluid sampling apparatus; and

(c) a reservoir that is in hydraulic communication with both said plurality of microneedles and said pumping apparatus;

wherein said reservoir receives fluid that flows through said plurality of microneedles upon manual actuation of said pumping apparatus, wherein said fluid sampling apparatus has

a fluidic passageway that is in hydraulic communication with said plurality of microneedles and said reservoir; and

wherein said first surface is located on a first end of said fluid sampling apparatus, and said second surface is located on a second end of said fluid sampling apparatus that is distal from said first end, and

wherein said fluid sampling apparatus further comprises a fluidic output port that facilitates communication with an external electrochemical sensor.

2. A fluid sampling apparatus, comprising:

(a) a plurality of microneedles accessible on a first surface of said fluid sampling apparatus;

(b) a manually-operated pumping apparatus accessible on a second surface of said fluid sampling apparatus; and

(c) a reservoir that is in hydraulic communication with both said plurality of microneedles and said pumping apparatus;

wherein said reservoir receives fluid that flows through said plurality of microneedles upon manual actuation of said pumping apparatus,

wherein said first surface is located on a first side of said fluid sampling apparatus, and said second surface is located on a second side of said fluid sampling apparatus, in which said first side is opposite from said second side,

wherein said fluid sampling apparatus further comprises (a) a member having a first end proximal to said reservoir and extending to a second end distal from said reservoir, (b) at least one electrode positioned on said extending member, and (c) a sensor pad that is in hydraulic communication with said reservoir; and

wherein said at least one electrode is in communication with said sensor pad, and

wherein said fluid sampling apparatus further comprises an electrical interface that converts an output of said sensor pad into an electrical signal;

a processing circuit that detects a value of said electrical signal and generates an output signal; and

a display device that indicates a value representative of said output signal.

3. A fluid sensing apparatus, comprising:

(a) a plurality of solid microneedles accessible on a first surface of said fluid sensing apparatus, said solid microneedles being coated on an exterior surface;

whereupon said solid microneedles making contact with a biological barrier, said coating on said microneedles acting as an transducer responsive to a property of a fluid of said biological barrier, and thereby generating an electrical signal in response to said fluid property;

(b) a member having a first end proximal to said coated microneedles and extending to a second end distal from said coated microneedles; and

(c) at least one electrode positioned on said extending member, wherein said at least one electrode is in communication with said coated microneedles,

wherein said fluid sensing apparatus further comprises an electrical interface that converts an output of said at least one electrode into an electrical signal;

a processing circuit that detects a value of said electrical signal and generates an output signal; and

a display device that indicates a value of said output signal.

4. The fluid sensing apparatus as recited in claim 3, wherein said processing circuit acquires a single reading from said transducer, thereby effectively implementing a one-touch reading system.

5. The fluid sensing apparatus as recited in claim 3, wherein said processing circuit acquires multiple readings from said transducer over a time interval, thereby effectively implementing a continuous measurement system.

6. The fluid sensing apparatus as recited in claim 5, wherein said processing circuit stores said multiple readings in a memory device, used in a later retrieval for trend analysis, or to be communicated to a remote device.

7. The fluid sensing apparatus as recited in claim 6, wherein said multiple readings represent one of:

raw data, averages, arithmetic means, maxima or minima.

8. A fluid sampling apparatus, comprising:

(a) an attachable/detachable portion that includes a plurality of microneedles, a reservoir, an optical sensor pad, and an optical window; and

(b) a main body portion that includes a receptacle to receive said attachable/detachable portion such that, when in position, the optical window faces said main body portion and the plurality of microneedles are accessible;

a light source and light detector; and

a manually-operated control actuator mounted on a surface of said main body portion that causes fluid to flow proximal to said plurality of microneedles;

wherein said reservoir receives fluid that flows through said plurality of microneedles upon manual operation of said control actuator, and said optical sensor pad exhibits a change in a physical property that is detected by said light detector as said light source shines light upon said optical sensor pad.

9. The fluid sampling apparatus as recited in claim 8, wherein said manually-operated pumping apparatus comprises a pushbutton-like device, which:

(a) is actuated at least once to cause a pressure differential that withdraws fluid through said microneedles, or (b) is pre-cocked in a first position, and then released by said manual actuation to move to a second position that causes cause a pressure differential that withdraws fluid through said microneedles.

10. The fluid sampling apparatus as recited in claim 8, further comprising:

a display device that indicates a value representative of an output signal produced by said light detector, or which displays a message to the user.

11. The fluid sampling apparatus as recited in claim 8, further comprising:

an electrical circuit that provides electrical current to tips of said microneedles, thereby heating said microneedle tips while the microneedles are inserted in skin to facilitate extraction of interstitial fluid.

12. The fluid sampling apparatus as recited in claim 8, further comprising:

a coating layer of material on tips of said plurality of microneedles, said coating layer absorbing some interstitial fluid of skin, and producing a chemical, electrochemical, or optochemical reaction thereto.

13. A fluid sampling apparatus, comprising:

(a) an attachable/detachable portion that includes a plurality of microneedles, a reservoir, an electrochemical sensor pad, and at least one electrode in communication with said sensor pad; and

(b) a main body portion that includes a receptacle to receive said attachable/detachable portion such that, when in position, the at least one electrode faces said main body portion and the plurality of microneedles are accessible;

an electrical sensor; and

a manually-operated pumping apparatus accessible on a surface of said main body portion;

wherein said reservoir receives fluid that flows through said plurality of microneedles upon manual actuation of said pumping apparatus, and said electrochemical sensor pad exhibits a change in a physical property that is detected by said at least one electrode which outputs an electrical signal, and said electrical sensor is in communication with said at least one electrode and generates an output signal in response to said electrical signal, and

wherein said fluid sampling apparatus further comprises a display device that indicates a value representative of said output signal produced by said electrical sensor, or which displays a message to the user.

14. A fluid sampling apparatus, comprising:

a plurality of microneedles and an associated substrate that is in mechanical communication with a plunger, said plunger being manually operable;

a housing that contains a variable volume chamber and which contains a flexible membrane that deflects upon movement of said plunger, said membrane'"'"'s deflection causing a variation in the volume of said chamber; and

an output port that is in hydraulic communication with said variable volume chamber;

wherein upon actuation of said plunger in one direction, said microneedles being pushed into and piercing a biological barrier; and

upon actuation of said plunger in a second, opposite direction, fluid from said biological barrier is withdrawn into said variable volume chamber and thereby directed to said output port,

wherein said fluid sampling apparatus further comprises a sensor that generates an electrical signal in response to a change in a property of said fluid after said fluid travels through a tube that is in hydraulic communication with said output port, and a display device that indicates a value of said electrical signal produced by said sensor, or which displays a message to the user.

15. A replaceable cartridge, comprising:

a plurality of microneedle strips attached to a movable substrate of material, each of said microneedle strips including;

a plurality of microneedles accessible to a user, a sensor that is in communication with a fluid that flows through said microneedles, and a signal transducer that is in communication with said sensor;

wherein said signal transducer of a first of the plurality of microneedle strips generates an electrical signal that is communicated to an output port, and wherein said movable substrate of material is indexable to a next position that will make a second of the plurality of microneedle strips accessible to a user.

16. The replaceable cartridge as recited in claim 15, wherein said movable substrate of material comprises a web of material that moves from a source reel to a take-up reel, upon indexing of the substrate.

17. The replaceable cartridge as recited in claim 15, wherein said movable substrate of material comprises a circular disc that contains said plurality of microneedle strips near the disc'"'"'s outer diameter.

18. The replaceable cartridge as recited in claim 15, wherein said signal transducer comprises one of:

(a) at least one electrode, (b) an electron sensor, or (c) an optical coupler.

19. The replaceable cartridge as recited in claim 15, further comprising:

(a) a signal conditioning circuit that converts said electrical signal generated by said signal transducer into a second signal;

(b) a personal data assistant that has an electrical plug-in port that attachably/detachably mates with said output port, and receives said second signal from said cartridge;

said personal data assistant including a processing circuit, a memory circuit, a display controller circuit, and a visible display that is discernible by a human eye; and

said personal data assistant including a computer program that measures a property of said second signal and displays a corresponding numeric quantity.

20. The replaceable cartridge as recited in claim 19, wherein said second signal comprises one of:

(a) an electrical signal, (b) an acoustic signal, (c) a magnetic signal, or (d) an electromagnetic signal having a wavelength so as to be one of;

(i) an optical signal, (ii) a microwave signal, or (iii) a radio-frequency signal.

21. The replaceable cartridge as recited in claim 15, further comprising:

(a) a signal conditioning circuit that converts said electrical signal generated by said signal transducer into a second signal;

(b) a self-contained display unit which comprises;

an electrical plug-in port that attachably/detachably mates with said output port, and receives said second signal from said cartridge, a processing circuit, a memory circuit, a display controller circuit, and a visible display that is discernible by a human eye; and

a computer program that measures a property of said second signal and displays a corresponding numeric quantity.

22. The replaceable cartridge as recited in claim 21, wherein said second signal comprises one of:

(a) an electrical signal, (b) an acoustic signal, (c) a magnetic signal, or (d) an electromagnetic signal having a wavelength so as to be one of;

(i) an optical signal, (ii) a microwave signal, or (iii) a radio-frequency signal.

23. The replaceable cartridge as recited in claim 21, further comprising:

a manually-operable actuator that advances said movable, indexable substrate of material to said next position.

24. The replaceable cartridge as recited in claim 21, further comprising:

a discharge port where spent microneedle strips are automatically ejected after said movable, indexable substrate of material has been advanced to said next position.

25. A single-use microneedle system, comprising:

an array of microneedle members that protrude from a base member, said microneedle members being of a size, shape, and material so as to penetrate through a stratum corneum of skin when placed against said skin; and

a self-destruct mechanism that renders said microneedle members incapable of penetrating said stratum corneum after being operative upon said microneedle members, said self-destruct mechanism comprising one of;

(a) a heat source, (b) an electrical energy source, (c) a optical energy source, (d) a chemical reaction, (e) a mechanical member that exerts a force, or (f) a material that permanently encapsulates the microneedle members.

26. The single-use microneedle system as recited in claim 25, wherein said self-destruct mechanism either melts, chemically alters, or mechanically alters said array of microneedle members so as to:

(a) shorten a length of the array of microneedle members to an extent that they cannot penetrate entirely through said stratum corneum, (b) deform a shape of a tip or a side wall of said array of microneedle members to an extent that they cannot sufficiently pierce said stratum corneum, or (c) break or crush said array of microneedle members flat entirely against said base member.

27. The single-use microneedle system as recited in claim 25, wherein said heat source comprises:

an electrical heating element, a electrical lamp, a laser light source, or a chemical reaction.

28. The single-use microneedle system as recited in claim 25, wherein said mechanical member comprises one of:

(a) a pivotable crushing member, (b) a shear deflection member, (c) a reciprocal crushing member, or (d) a mechanical flattening structure; and

wherein said mechanical member either breaks or crushes said array of microneedle members.

29. The single-use microneedle system as recited in claim 25, wherein said array of microneedle members are either solid or hollow.

30. The single-use microneedle system as recited in claim 25, further comprising:

a replaceable cartridge that contains a plurality of said array of microneedle members attached to a movable substrate of material, said cartridge having an opening that allows a first one of said plurality of said array of microneedle members to be accessible to a user;

wherein said movable substrate of material indexes to a next position that will make a second one of the plurality of said array of microneedle members accessible to a user, and wherein said first one of the plurality of said array of microneedle members simultaneously automatically indexes to said self-destruct mechanism, where said first one of the plurality of said array of microneedle members is rendered incapable of penetrating said stratum corneum.