DEVICE AND METHOD FOR EXTRACTING FLUIDS FROM TISSUE

Abstract

The present invention relates to methods and devices for extraction of bodily fluids from tissue by creating microscopic openings in the outermost layers of the skin and drawing out the fluid. One embodiment of the invention is a cylindrical hollow member, made of electrically conducting material, with sharpened edges.

Claims

1. A blood glucose measurement device for single handed use, comprising: a body having first and second ends and an electrically conducting surface which serves as a counterelectrode for impedance measurement; a drilling device with a disposable cutter at one end of the body, wherein the cutter is an electrically conducting element which plugs into an electrically conducting receptacle in the device, and wherein the cutter initially rotates to create a breach in skin tissue selected from the stratum corneum and the epidermis; a drive assembly disposed inside the body that, after the breach is created in the skin tissue, moves the cutting element in a dithering manner, repeatedly into and away from the skin thereby withdrawing fluid from the breach in the tissue; a test strip port for positioning a test strip adjacent to the cutter for collection of body fluid from the breach of the skin tissue; an electronic control module disposed inside the body for controlling the skin cutting element such that the dithering motion stops once adequate fluid has been collected for the test strip; and measurement means for determining blood glucose in the body fluid collected by the test strip; and a readout display for the blood glucose level, disposed on the surface of the device body.

2. The device of claim 1, wherein the cutter rotates as it moves into and out of the tissue.

3. The device of claim 1, wherein the surface of the cutter is roughened to enhance the surface tension between the cutter and the body fluids, thereby improving the extraction of the bodily fluid from the tissue.

4. The device of claim 1, wherein the cutter comprises a hollow member that dithers in and out of the skin to create an opening and collect fluid in the bore of the cutter.

5. The device of claim 4, wherein the hollow cutter rotates as it moves into and out of the tissue.

6. The device of claim 1, wherein the cutter rotates prior to and during the process of creating a hole, but does not rotate subsequently.

7. The device of claim 1, wherein the cutter comprises a hollow cylindrical member into which the blood or interstitial fluid is drawn for subsequent analysis.

8. A method of extracting bodily fluids from tissue which comprises repeating the following steps using the device of claim 1: moving the cutting element toward the skin in a dither mode wherein the cutter is moved in small steps toward and away from the skin with a small bias in movement toward the skin, monitoring an electrical impedance, and reversing the direction of movement when a preset level of decrease in the electrical impedance is detected; the procedure is repeated until a predetermined quantity of bodily fluid is collected.

9. The method of claim 8, wherein as the cutter moves into the tissue, it encounters fluid; as the cutter starts to retract, and move away from the skin, the cutter pulls the fluid up, thus enlarging the bolus of fluid at the surface of the hole.

10. The method of claim 9, wherein an analyte sensing element is positioned near the skin surface and proximate to the cutter, such that when the fluid is drawn out of the skin, it contacts the sensing element.

11. The method of claim 8, wherein the cutter rotates as it moves into and out of the skin.

12. The method of claim 11, wherein the rotating cutter creates an opening in the skin large enough to produce a drop of blood or interstitial fluid.

13. The method of claim 12, wherein the blood or interstitial fluid is drawn out of the hole by surface tension.

14. The method of claim 8, wherein a non-rotating cutter that dithers through the skin, creates an opening, subsequently draws blood or interstitial fluid out by surface tension.

15. The method of claim 8, wherein the surface of the cutter is roughened to enhance the surface tension between the cutter and the body fluids, thereby improving the extraction of the bodily fluid from the tissue.

16. The method of claim 8, wherein the cutter comprises a hollow member that dithers in and out of the skin to create an opening and collect fluid in the bore of the cutter.

17. The method of claim 16, wherein the hollow cutter rotates as it moves into and out of the tissue.

18. The method of claim 8, wherein the cutter moves in a dither manner until a sufficient amount of blood or interstitial fluid is collected for blood glucose measurement.

19. A body fluid testing device for single handed use, comprising: a device body having first and second ends and an electrically conducting surface which serves as the counterelectrode for impedance measurement; a drilling device with a disposable cutter at one end of the body, wherein the cutter is an electrically conducting element which plugs into an electrically conducting receptacle in the device, and wherein the cutter initially rotates to create a breach in skin tissue selected from the stratum corneum and the epidermis; a drive assembly disposed inside the body that, after the breach is created in the skin tissue, moves the cutting element in a dithering manner, repeatedly into and away from the skin thereby withdrawing fluid from the breach in the tissue; a test strip port for positioning a test strip adjacent to the cutter for collection of body fluid from the breach of the skin tissue; an electronic control module disposed inside the body for controlling the skin cutting element such that the dithering motion stops once adequate fluid has been collected for the test strip; measurement means for determining components in the body fluid collected by the test strip; and a readout display for the body fluid components, disposed on the surface of the device body.

20. The device of claim 19, wherein the body fluid components measured by the device are selected from the group consisting of blood glucose testing, blood gas and electrolytes analysis, rapid coagulation testing, rapid cardiac markers, drugs, pregnancy testing, food pathogens, hemoglobin, infectious disease, and cholesterol screening.

21. The device of claim 19, wherein control of the cutter penetration into the skin tissue is based on the device sensing a pre-set electrical impedance.

22. The device of claim 22, wherein the cutter can, on sensing a pre-set electrical impedance, move further into the skin tissue for a predetermined distance before retracting.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0045] FIG. 1 is a schematic of a preferred embodiment of the invention: a cutter 2 in proximity to skin 1. The cutter is driven toward/away from the skin by an up/down drive mechanism. The cutter may be rotated throughout all or part of the process by the rotational drive mechanism. The impedance sensor continually measures the electrical impedance between the cutter 2 and the counterelectrode 3. The electronic control module controls the rotational and translational movement of the cutter. Once a fluid sample is collected, the analyte measurement module determines the concentration of one or more analytes in the fluid. The concentrations of the analytes are displayed by the display module.

[0046] FIG. 2 is a schematic of a preferred embodiment of the blood sampling process. The cutter is driven toward the skin in dither mode (Panel 1). When the skin breaches the stratum corneum of the skin, it encounters the low electrical impedance of the epidermal tissue (Panel 2); it retracts from the skin leaving an opening in the stratum corneum (Panel 3). As the cutter pulls out, interstitial fluid appears out of the opening (Panel 4). As the cutter drives down toward the skin, interstitial fluid/blood flows out of the skin, when the fluid contacts the cutter, a low impedance is sensed causing the cutter to retract (Panel 5). During the retraction, surface tension forces enable the cutter to drag the bolus out, enlarging it (Panel 6).

[0047] FIG. 3 shows the setup to demonstrate the proof-of-concept of the invention. The device 1 is placed on the back of hand (as an example site). The device 1 has two motors, 3 to drive the cutter 12 toward and away from the skin 18 and 4 to rotate the cutter around its long axis. A lead screw mechanism 8 is used to drive the movable carriage 6. The foot of the device 13 has a foot ring 14 with a central opening that enables the skin to bulge in toward the cutter to create a firm surface for the cutter to contact. An electrically conducting ring 15 is used as a counterelectrode. In certain embodiments a pair of ECG electrodes placed over the skin serves as the counterelectrode. A glucose sensing strip 16 is inserted into the foot ring 14, and the other end of the strip is inserted into a glucose meter 17. A cutter 12 is shown as a hollow tube that tapers near the tip to form a sharp cutting edge (such as a sharpened, even bottomed small hypodermic tubing stock).

[0048] FIG. 4 shows the sampling of interstitial fluid using an embodiment of the invention. Successive panels show the intact skin, appearance of interstitial fluid, fluid bolus contacting the cutter, and the lifting of the bolus by the tip of the cutter thus enlarging the bolus.

[0049] FIG. 5 shows the sampling of blood using an embodiment of the invention. Successive panels show the intact skin, appearance of blood, blood bolus contacting the cutter, and the lifting of the bolus by the tip of the cutter thus enlarging the bolus.

[0050] FIG. 6 shows measurement of blood glucose using interstitial fluid. The glucose strip is placed horizontally on the skin with the capillary opening located close to the cutter (left). As the interstitial fluid emerges from the skin, it is taken up by the capillary tube in the glucose strip (right).

[0051] FIG. 7 shows an alternate arrangement of the glucose strip, the strip is now placed vertically with the capillary in the strip contacting the skin (left). As the blood bolus appears from the skin, it is absorbed into the capillary tube (right).

[0052] FIGS. 8-11 illustrate a proposed commercial embodiment of an integrated unit, combining the drilling unit, the hollow rotating and dithering cutter, and conventional glucose monitoring technology, in a one hand blood glucose device.

DETAILED DESCRIPTION OF THE INVENTION

[0053] The fluid collection method presented here results from the interaction of different forces acting on a volume of blood that appears from the opening made in the skin. The liquid contracts its surface area to maintain the lowest surface energy, causing it take a spherical shape. But, skin is not a flat, homogeneous surface; the uneven surface of the skin causes the blood drop to spread to a non-spherical shape. The surface tension of the blood drop determines its shape. A liquid drop (blood in this case) resting on a solid surface (skin) forms an angle called a contact angle between the liquid-solid interface and the liquid-vapor (air) interface. When a solid, such as a cutter, is immersed or pulled out of the blood drop, an advancing or receding contact angle is established. As the cutter is withdrawn from the blood, it imposes a force on the blood molecules, drawing them out along with the cutter. This, in turn, expands the volume of the blood bolus. The height to which the cutter deforms the blood drop depends on the wettability of the cutter (material make-up of the cutter), diameter of the cutter and the speed of retraction.

[0054] FIGS. 1-7 provide details regarding experiments performed using the apparatus and techniques described therein. These experiments are but a few of the possible applications and should not be viewed as a compressive list or discussion. The experiments were conducted with the setup shown in FIG. 3. The device 1 was placed on the back of hand (as an example site). The device 1 has two motors, 3 to drive the cutter 12 toward and away from the skin 18 and 4 to rotate the cutter around its long axis. A lead screw mechanism 8 is used to drive the movable carriage 6. The foot of the device 10 has a foot ring 14 that contacts the skin. An electrically conducting ring 15 is used as a counterelectrode. In certain embodiments a pair of ECG electrodes contacting skin 18 served as the counterelectrode. A glucose sensing strip 16 is inserted into the foot ring 14, and the other end of the strip is inserted into a conventional glucose meter 17.

EXAMPLES

[0055] The following non-limiting examples serve to illustrate certain embodiments of the invention but are not to be construed as limiting. Variations and additional or alternative embodiments will be readily apparent to the skilled artisan on the basis of the disclosure provided herein.

Example 1

Sampling of Interstitial Fluid

[0056] A 0.014 diameter cutter with a short flute (0.015 long) was mounted in a PathFormer device (1 of FIG. 3). The device uses skin impedance as a trigger to limit the depth of penetration into the skin. The device was used in the dither mode in this experiment. A pair of Norotrode 20 electrodes stuck on the skin (away from the site of drilling) was used as counterelectrodes. The device was set to 15 k trigger resistance. After the 10th dither, clear interstitial fluid emerged from the skin. At 30.sup.th dither, there was a slight pricking sensation at which point a large bolus of interstitial fluid appeared (FIG. 4). Subsequently, the cutter started moving slowly into the bolus and drawing the fluid out. When the device was turned off and lifted off the skin, blood appeared from the site mixing with the bolus of interstitial fluid.

Example 2

Sampling of Blood

[0057] A 0.014 diameter endmill was used as the cutter. The device was set to 15 k trigger resistance. After 10 dithers, blood appeared via the opening, but the cutter did not appear to touch the skin during subsequent dithering (FIG. 5). The hole was clean and circular, but skin fragments were stuck to the cutter.

Example3

Sharpened Stainless Tube as Cutter

[0058] A stainless steel needle tube with its ends sharpened was used as the cutter (FIG. 5). The outside diameter of the tube was 0.024. The tube was epoxied to a cylindrical brass holder with a 0.025 hole through it. The back end of the tube was left open. The standard dither protocol was used: dither down into the skin until the preset trigger impedance (15 k in this case) was reached, then retract and repeat the dither process. Within the first two dithers, blood started appearing, the cutter kept retracting, reaching down to the top of the blood bolus, pulling the bolus up, the contact between the bolus and the cutter breaks, the cutter goes down again. There was no sensation during the procedure. There was an ample bolus of blood at the end of the experiment (around 30 dithers). The cutter was clean on the inside, but there was a blood stain around the outside surface close to the end.

Example 4

Abraded Cutter

[0059] A solid with a rough surface has a higher wettability than a smooth cutter. So, a 0.020 diameter endmill was abraded by directing a stream of high speed aluminum oxide powder on it. The cutter cut into the skin on the first dither producing a bolus of blood. The bolus continued to increase in size over the next 10 dithers. The cutter subsequently reached the tip of the bolus and pulled back on every dither.

Example 5

Integrated Blood Sampling and Blood Glucose MeasurementVertically Aligned Strip

[0060] A 0.024 diameter flat bottomed endmill was used as the cutter. A glucose strip was located close to the cutter by placing it vertically into a slot in the foot ring (FIG. 7). The glucose sensing strip was inserted into the glucose meter just before the drilling commenced. The device was operated in the dither mode with the retraction on low impedance being longer than the downward travel. Interstitial fluid started flowing out after the 4.sup.th dither. The cutter started drawing the fluid out with every subsequent dither.

[0061] The glucose strip was located away from the bolus, so the strip was moved closer to the bolus by the 23.sup.rd dither; it took 10 more dithers to get enough fluid into the meter. The meter read 115 mg/dL at the end of the procedure. The cutter looked clean and sharp (although a bit more shiny) after drilling.

Example 6

Integrated Blood Sampling and Blood Glucose MeasurementHorizontally Aligned Strip

[0062] A stainless steel needle (23 gauge) with the end sharpened by abrading the outside and inside surface of the needle end was used (FIG. 6). The outside diameter of the needle was 0.024. The needle was epoxied to a cylindrical brass holder with a 0.025 hole through it. The back end of the needle was left open. The standard dither protocol was used: dither down into the skin until the preset trigger impedance (15 k in this case) was reached, then retract and repeat the dither process. But, the drill stopped spinning after it encountered low impedance for the fifth time. A glucose strip was placed horizontally in the footer ring slot. The strip capillary tip was located very close to the needle cutter. There was very little blood from the dithering process. After around 1 minute, the strip had enough blood to make a measurement (91 mg/dL).

Example 7

One Hand Integrated Unit

[0063] As illustrated in FIGS. 8-11, another embodiment of the present invention is directed to a proposed commercial embodiment of a one hand integrated blood glucose measurement unit, based on the concepts discussed above regarding FIGS. 1-7. Conventional blood glucose sensing circuitry is employed as the measurement means for the blood glucose meter. Such circuitry is well known to those skilled in the art. See, for example, U.S. Pat. No. 4,787,398, which is hereby incorporated herein by reference.

[0064] As shown in FIG. 8, in this proposed commercial configuration, the hand held device is approximately the size and shape of an oversized white board marker. The device foot that rests against the patient's skin accepts insertion of a typical disposable blood glucose capillary strip together with a disposable piercing cutter.

[0065] As shown in FIG. 9, the device housing is electrically conductive, and once the device has sensed the electrical impedance of the controlling hand gripping the device and the foot of the unit placed securely against the skin, a ready signal appears in the readout. The patient then presses a button on the device causing the cutter to begin spinning and advancing toward the test site.

[0066] As shown in FIG. 10, once the cutter penetrates the dead skin cells of the stratum corneum, a great reduction in electrical impedance is detected. This change causes the cutter to stop spinning and immediately retract from the conduit created through the stratum corneum. The slight pressure of the foot of the device surrounding the test site causes interstitial fluid and blood to fill the conduit through the stratum corneum simultaneously as the cutter retracts out of the conduit.

[0067] This retraction occurs before the cutter reaches and damages the underlying living tissue and the nerves. Thus, there is no sensation of pain or damage to the living epidermis tissues. Right after the first retraction, the device goes into dither mode, rapidly advancing and retracting, each advance is quickly halted by the drop in electrical impedance when the cutter touches the blood and the cutter is again withdrawn.

[0068] Each time the cutter touches the liquid, surface tension between the cutter and liquid lifts more blood out of the conduit. As a result of the bolus building atop the opening, the cutter never reenters the patient's skin a second time. With each dither, the surface tension caused by the cutter's contact with the fluids exiting the conduit causes the bolus to continue growing until the blood comes into contact with the capillary component of the test strip.

[0069] As shown in FIG. 11, once the test strip has collected enough blood to produce a reading, dithering stops, an audio cue sounds and the patient's blood glucose reading appears in the device display. It takes approximately five seconds from device activation to final glucose readout. The entire process is painless. The conduit through the stratum corneum heals quickly without leaving tissue damage. This blood harvesting capability may be used for other blood chemistry as well.

[0070] As used herein, the singular forms a, an and the include plural unless the context clearly dictates otherwise. Moreover, when an amount, concentration, or other value or parameter is given as either a range, preferred range, or a list of upper preferable values and lower preferable values, this is to be understood as specifically disclosing all ranges formed from any pair of any upper range limit or preferred value and any lower range limit or preferred value, regardless of whether ranges are separately disclosed. Where a range of numerical values is recited herein, unless otherwise stated, the range is intended to include the endpoints thereof, and all integers and fractions within the range. It is not intended that the scope of the invention be limited to the specific values recited when defining a range.

[0071] From the foregoing, it will be appreciated that although specific examples have been described herein for purposes of illustration, various modifications may be made without deviating from the spirit or scope of this disclosure. It is therefore intended that the foregoing detailed description be regarded as illustrative rather than limiting, and that it be understood that it is the following claims, including all equivalents, that are intended to particularly point out and distinctly claim the claimed subject matter.