(12) United States Patent
`Whitson
`
`(54) HOLLOW MlCRONEEDLE PATCH
`
`(75)
`
`Inventor: Robert C. Whitson, Goshen, IN (US)
`
`(73) A5Signee: Bayer Corporation, Elkhart, IN (US)
`( * ) Notice:
`
`Subject to any disclaimer, the term of this
`patent is extended or adjusted LLnder 35
`U.S.C. 154(b) by 155 days.
`
`(21) Appl. No.: 09/877,519
`Jun. 11, 2001
`(22) Filed:
`Prior Publication Data
`
`(65)
`
`US 2002/0006355 Al .Jan. '17, 2002
`
`Related U.S. Application Data
`
`(60) Provisional application
`No. 60/217,424, filed oo Jul. 11,
`2000.
`(51) Int. Cl.7 ......................... GOIN 27/26; GOlN 31/22
`(52) U.S. Cl .......................... 600/345; 600/365; 422/56;
`422/58; 422/82.05; 436/169
`(58) Field of Search ................................. 600/345, 347,
`600/316, 317, 322, 341, 365, 367, 368,
`583; 604/19-22, 506, 46, 272, 274, 307,
`27; 422/56, 58, 82.05; 436/169
`
`(56)
`
`References Cited
`
`U.S. PATENT DOCUMENTS
`
`I lllll llllllll Ill lllll lllll lllll lllll lllll lllll lllll lllll llllll llll llll llll
`
`US006603987B2
`(10) Patent No.:
`US 6,603,987 B2
`(45) Date of Patent:
`Aug. 5, 2003
`
`6,091,975 A • 7/2000 Daddona et al. ............ 600/345
`6,219,574 Bl * 4/2001 Cormier et al. ............... 604/20
`6,256,533 Bl * 7/2001 Yuzhakov et al.
`............ 604/21
`6,334,856 Bl * 1/2002 Nlen et al. ................. 604/191
`6,379,324 Bl * 4/2002 Gartstein et al. ............. 604/22
`6,440,096 Bl * 8/2002 Lastovich el al.
`.. .......... 604/27
`6,501,976 Bl * 12/2002 Sohrab ....................... 6001347
`l/2003 Prausnitz et al. ........... 604/272
`6,503,231 Bl *
`2002/0155737 Al * 10/2002 Roy et al. ..................... 439/66
`2002/0177764 Al * 11/2002 Sohrab ....................... 6001345
`2003/0045837 Al * 3/2003 Delmore et al. .............. 604/46
`
`FOREIGN PATENT DOCUMENTS
`
`WO
`
`00/22977
`
`• 4/2000
`
`* cited by examiner
`
`Primary Examiner-John A Jeffery
`(74) Allomey, Agent, or Firm-Jerome L. Jeffers
`(57)
`
`ABSTRACT
`
`A test strip is provided for use in lhe delermination o( tbe
`
`concentration of an a cbemical in blood. Tbe test strip
`
`comprises a plurality of microneedles and a lest area. Each
`microneedle is adapted to pllOCture skin and to draw blood.
`The test area is in fluid communication with the microo­
`eedles. The test area contains a reagent adapted lo produce
`
`a reaction indicative of the concentration of the chemical in
`
`blood.
`
`5,457,041 A * 10/1995 Gioavco el al. ......... 435/172.l
`
`19 Claims, 10 Drawing Sheets
`
`200
`�
`
`234
`\
`
`230
`
`230
`
`202
`
`�
`202
`
`204
`
`AGAMATRIX, INC. EXHIBIT NO. 1023
`Page 1 of 15
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`

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`U.S. Patent
`
`Aug. S, 2003
`
`Sheet 1 of 10
`
`US 6,603,987 B2
`
`100
`
`�
`
`102
`
`0
`
`104
`
`b
`
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`106
`
`FIG. 1
`(Prior Art)
`
`AGAMATRIX, INC. EXHIBIT NO. 1023
`Page 2 of 15
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`

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`U.S. Patent
`
`Aug. 5, 2003
`
`Sheet 2 of 10
`
`US 6,603,987 B2
`
`120
`
`\
`
`122
`
`FIG. 2
`(Prior Art)
`
`AGAMATRIX, INC. EXHIBIT NO. 1023
`Page 3 of 15
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`

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`U.S. Patent
`
`Aug. s, 2003
`
`Sheet 3 of 10
`
`US 6,603,987 B2
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`AGAMATRIX, INC. EXHIBIT NO. 1023
`Page 4 of 15
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`

`

`U.S. Patent
`
`Aug. 5, 2003
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`Sheet 4 of 10
`
`US 6,603,987 B2
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`AGAMATRIX, INC. EXHIBIT NO. 1023
`Page 5 of 15
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`U.S. Patent
`
`Aug. 5, 2003
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`Sheet 5 of 10
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`US 6,603,987 B2
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`
`AGAMATRIX, INC. EXHIBIT NO. 1023
`Page 6 of 15
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`

`

`U.S. Patent
`
`Aug. 5, 2003
`
`Sheet 6 of 10
`
`US 6,603,987 B2
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`AGAMATRIX, INC. EXHIBIT NO. 1023
`Page 7 of 15
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`

`

`U.S. Patent
`
`Aug. 5, 2003
`
`Sheet 7 of 10
`
`US 6,603,987 B2
`
`300
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`302
`
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`
`AGAMATRIX, INC. EXHIBIT NO. 1023
`Page 8 of 15
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`

`

`U.S. Patent
`
`Aug. 5, 2003
`
`Sheet 8 of 10
`
`US 6,603,987 B2
`
`320
`
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`
`FIG. 10
`
`AGAMATRIX, INC. EXHIBIT NO. 1023
`Page 9 of 15
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`

`

`U.S. Patent
`
`Aug. 5, 2003
`
`Sheet 9 of 10
`
`US 6,603,987 B2
`
`350
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`�
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`200
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`
`AGAMATRIX, INC. EXHIBIT NO. 1023
`Page 10 of 15
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`

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`AGAMATRIX, INC. EXHIBIT NO. 1023
`Page 11 of 15
`
`

`

`US 6,603,987 B2
`
`1
`HOLLOW MICRONEEDLE PATCH
`
`This application claims benefit of Provisional Applica­
`tion Ser. No. 60/217,424 filed Jul. 11, 2000.
`
`2
`larger than necessary and consequently take a greater time to
`heal. The greater the amount of time for the wound to heal
`translates into a longer period of time in which the wound is
`susceptible to infection.
`Another problem associated with some conventional
`blood glucose monitoring devices is that the user's blood
`physically contacts the elements within the testing unit.
`Cross-contamination can be a problem if the monitoring
`device is used by more than one user such as a clinical
`
`5
`
`10 setting.
`
`FIELD OF THE INVENTION
`The present invention relates generally to blood monitor­
`ing devices, and, more particularly, to a test patch for
`painlessly obtaining a sample of blood.
`BACKGROUND OF THE INVENTION
`It is often necessary to quickly and painlessly obtain a
`sample of blood and perform a quick analysis of the blood.
`One example of a need for painlessly obtaining a sample of
`blood is
`system where a user must frequently use the system to
`monitor the user's blood glucose level.
`Those who have irregular blood glucose concentration
`levels are medically required to regularly self-monitor their
`blood glucose concentration level. An irregular blood glu­
`cose level can be brought on by a variety of reasons
`including illness such as diabetes. The purpose of monitor­
`ing the blood glucose concentration level is to determine the
`blood glucose concentration level and then to take corrective
`
`in connection with a blood glucose monitoring 15
`
`SUMMARY OF THE fNVENTION
`
`FIG.12 is an embodiment of a blood glucose monitoring
`
`system according to a ninth alternative embodiment of the
`present invention.
`
`According to one embodiment of the present invention, a
`test strip is provided for use in the determination of the
`concentration of a chemical in blood. The test strip com­
`prises an array o( microneedles and a test area. Each
`microoeedle is adapted to puncture skin and to draw blood.
`The test area is in fluid communication with the micron-
`eedlcs. The test area contains a reagent adapted to produce
`20 a reaction indicative or the concentration of the chemical in
`blood.
`The above summary o( the present invention is not
`intended to represent each embodiment, or every aspect, of
`the present invention. Additional features and benefits of the
`present invention will become apparent from tbe detailed
`description, figures, and claims set Corth below.
`BRIEF DESCRIPTION OF THE DRAWINGS
`Other objects and advantages of the invention will
`become apparent upon reading
`the Collowing detailed
`description in conjunction with the drawings in wb.ich:
`FIG. 1 is a top view of a prior art blood glucose testing
`device;
`FIG. 2 is a perspective view of a prior art lance;
`FIG. 3 is a perspective view of a microoeedle patch
`accorrung to one embodiment of the present invention;
`FIG. 4 is a cross-sectional view of the embodiment of the
`microneedle patch illustrated in f.IG. 3;
`FIG. 5 is another cross-sectional view of the embodiment
`of the microneedle patch illustrated in FIG. 3;
`FIG. 6 is a collection point of a microoeedle according to
`a second alternative embodiment of the present invention;
`FIG. 7 is a collection point of a microneedle according to
`a third alternative embodiment of the present invention;
`FIG. 8 is a collection point of a microneedle according to
`a forth alternative embodiment of tbe present invention;
`FIG. 9 is an embodiment of a blood glucose monitoring
`device for use in conjunction with a microneedle patch
`according lo a sixth alternative embodiment of tbe present
`invention;
`FIG. 10 is an embodiment of a blood glucose monitoring
`device for use in conjunction with a microneedle patch
`according to a seventh alternative embodiment of the present
`invention;
`FIG. 11 is an embodiment of a blood glucose monitoring
`system according to an eighth alternative embodiment of the
`present invention; and
`
`action, based upon whether the level is too high or too low, 25
`
`35
`
`to bring the level back within a normal range. The failure to
`take corrective action can have serious implications. When
`blood glucose levels drop too low-a condition known as
`hypoglycemia-a person can become nervous, shaky, and
`confused. That person's judgment may become impaired 30
`and that person may eventually pass out. A person can also
`become very ill if their blood glucose level becomes too
`high-a condition known as hyperglycemia. Both
`conditions, hypoglycemia and hyperglycemia, are both
`potentially life-threatening emergencies.
`One method of monitoring a person's blood glucose level
`is with a portable, band-held blood glucose testing device. A
`prior art blood glucose testing device 100 is illustrated in
`FIG. 1. The portable nature of these devices 100 enables the
`users to conveniently test their blood glucose levels wher- 40
`ever the user may be. The glucose testing device contains a
`test sensor 102 to harvest the blood for analysis. The device
`100 contains a switch 104 to activate the device 100 and a
`display 106 to display the blood glucose analysis results. lo
`order to check the blood glucose level, a drop of blood is 45
`obtained from the fingertip using a lancing device. A prior
`art lancing device 120 is illustrated in FIG. 2. The lancing
`device 120 contains a needle lance 122 to puncture the skin.
`Some lancing devices implement a vacuum to facilitate the
`drawing of blood. Once the requisite amount of blood is 50
`produced on the fingertip, the blood is harvested using the
`test sensor 102. The test sensor 102, which is inserted into
`a testing unit 100, is brought into contact with the blood
`drop. The test sensor 102 draws the blood to the inside of the
`test unit 100 which then determines the concentration of 55
`glucose in the blood. Once the results of the test are
`displayed on the display 106 of the test unit 100, the test
`sensor 102 is discarded. Each new test requires a new test
`sensor 102.
`One problem associated with some conventional lancing 60
`devices is that there is a certain amount of pain associated
`with the lancing of a finger tip. Diabetics must regularly
`self-test themselves several time per day. Each test requires
`a separate lancing, each of which involves an instance of
`pain for the user.
`Anotherproblem associated with some conventional lanc­
`ing devices is that the lacerations produced by the lances are
`
`65
`
`DETAILED DESCRIPTION OF THE
`PREFERRED EMBODIMENTS
`Referring now to FIG. 3, a bollow microneedle patch 200
`according to one embodiment of the present invention is
`
`AGAMATRIX, INC. EXHIBIT NO. 1023
`Page 12 of 15
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`US 6,603,987 B2
`
`3
`illustrated. The microneedle patch 200 comprises a plurality
`of bollow microneedles 202 coupled to a test chamber 204.
`Blood is moved through each of the plurality of microo­
`eedles 202 by capillary action to the test chamber 204. In the
`illustrated embodiment of the present invention, the plurality 5
`of hollow microoeedles 202 are arranged in a twenty by
`twenty array so that the microoeedle patch 200 includes four
`hundred hollow microneedles 202. The rnicroneedle patch
`200 is used to lance a user's skin and lo harvest a sample of
`blood. Essentially, the microoeedle patch 200 integrates the 10
`prior art test sensor 102 and tbe lance UO (discussed in
`conjunction with FIGS. 1 and 2) into a single unit.
`Each microneedle penetrates lhe skin to a depth of about
`two-hundredths of an inch (0.005 inch). The microneedles
`202 extend below lhe surface of the skin a distance sufficient 15
`to collect a sample of blood from the outermost layer of
`capillaries. Tbe skin's outer layer, called the stratum
`corneum, does not con1ain any nerve endings. The firs1
`extensive nerve layer is disposed below the outermost layer
`of capillaries. Because each of the microneedles 202 do nol 20
`con1act any nerves, the lancing of the skin and the collection
`of blood is essentially painless. Further, because the lacera­
`tions created in the skin are much smaller that 1hose created
`by a conventional Janee, the risk of infection is lessened and
`lhe bealing of the lacerations is expedited. The precise 25
`dimensions of the microoeedles 202 and the microoeedle
`200 patch are a function of several variables including the
`amounl o( blood to be harvested and the type of blood
`glucose analysis lo be used in conjunction with the microo­
`eedle patch 200.
`Referring now to FIGS. 4 and 5, the microneedle patch
`200 is illustrated pressed onto a user's skin 206 causing each
`o( the microneedles 202 10 penetrate the skin 206. Each of
`the micro needles 202 are hollow and have a collection point
`208 and an outlet 210. Tbe outlet 210 of each microoeedle 35
`202 is coupled to the test chamber 204. After penetrating 1be
`skin 206, blood 212 is collected though the collection point
`208 or each of the microneedles 202. The blood 212 is
`moved though an interior 214 of the bollow microneedles
`202 by capillary action to the test chamber 204. The requisite 40
`volume o( blood 212 necessary for accura1e testing is
`dependent on the type of glucose analysis employed. For
`example, 1he applicant has found thal al leas1 approximately
`one micro-liter of blood 2U is necessary to employ elec­
`trocbemical analysis to determine the blood glucose coo- 45
`centration. Each of the plurality of microneedles 202 draws
`a portion of the requisite volume of blood 212 into the test
`chamber 204 where the analysis occurs.
`A reagent 215 is incorporated in the test cbamber 204 of
`the microneedle patch 200. Once blood is moved into lhe 50
`test chamber 204, the glucose in the blood 212 reacts with
`the reagent 215 in the test chamber 204 to produce a
`detectable signal. Thal signal is then measured by a sensor
`which can measure the concentration of tbe glucose in tbe
`blood 212 based on the signal. The specific reagent 215 55
`incorpora1ed into the test chamber 204 is a function of the
`lype of sensing employed lo determine the concentration of
`glucose in 1he blood 2U.
`lo operation, a user can measure tbe concentration of the
`user's blood by pressing the microoeedle patch 200 onto the
`user's skin. Each o( l11e microneedles 202 lances the skin
`206. A quantity of blood 212 is moved by capillary action
`from the collection point 208 of each microoeedle 202 to tbe
`test chamber 204. The glucose in the blood 2U reacts with
`a reagent 215 incorporated into the tesl chamber 204 pro­
`ducing a signal indicative of 1he blood glucose concen1ra­
`lion. That signal is then measured with an appropriate sensor
`
`4
`in a blood glucose analyzer to determine the concentration
`of glucose in the user's blood. Once the blood glucose
`analyzer measures the signal produced by 1be reaction, the
`microoeedle patch 200 can be discarded.
`An advantage to the use of the microneedle patch 200 is
`that blood never comes into contact with !he blood glucose
`analyzer. Therefore, in addition to self-testing, the micron­
`eedle patch 200 may be used at a clinical level because
`cross-contamination is not an issue. For example, a doc1or
`may use a single blood glucose analyzer to test the blood
`glucose concentration for that doctor's patients. One
`microoeedle patch 200 would be used for each patient. The
`microneedle pa1ch is pressed onto the patient's skin and the
`signal produced by the reaction within the microoeedle
`patch 200 is read by a blood glucose analyz.er which never
`contacts lhe patient's blood. The blood glucose analyzer can
`be used again while the used microneedle patch 200, con­
`taining the sample of blood, is discarded.
`Referring to FIGS. 6, 7 and 8, three alternative embodi-
`ments o( the collection poinl o( each microneedle 202 is
`illustrated. Each microneedle 202 of 1he present invention is
`generally shaped as a hollow cylinder having cylindrical
`walls 230. lo FIG. 6, the collection point of the microoeedle
`202 is an angled collection poinl 232. A plane parallel to 1he
`angled collec1ion point 232 is disposed at an angle relative
`to the longitudinal axis of the microneedle 202.
`In another alternative embodiment, the microneedle 202
`bas a generally concave collection point 234 as illustrated in
`30 FIG. 7. Tbe generally cylindrical walls 230 of tbe micron­
`eedle 202 are formed upwardly sloping radially away from
`the longitudinal axis of tbe microneedle 202 at the collection
`poin1 234.
`In still ano1her alternative embodiment, the microneedle
`202 bas a generally convex collection poinl 236 is illustrated
`in FIG. 8. In the embodiment illustrated in FIG. 8, the
`generally cylindrical walls 230 of the microneedles 202 are
`formed downwardly sloping radially away from the longi­
`tudinal axis of the microneedle 202 at 1be collection point
`236. The shape of the alternative embodiments of the
`collections points illustrated io FIGS. 6-8 reduces surface
`tension at the collection point of the microneedle 202 thus
`facilitating the movement of blood from the collection point
`through !he hollow micro needle 202 to 1he test chamber 104.
`Colorimetric analysis is one type of analysis that can be
`utilized with the microneedle patch 200 of the present
`invention. The reaction of ibe glucose and a specific reagent
`produces a change in color, or a colorimetric reaction, which
`is indicative of the amount of glucose in the blood. That
`color change can be compared to a color chart, wherein the
`colors on the color chart were obtained using blood having
`a known glucose concentraiion, to determine the blood
`glucose concentration. The color change in the test chamber
`204 caused by the reaction of the glucose and the reagent
`215 can be read with a speclrophotometric instrument incor­
`
`porated into a glucose monitoring device for use wilh the
`
`patch 200. In such an embodiment where colorimertic
`sensing is employed, a back side 218 (FIG. 4) of the test
`sensor 204 may be transparent allowing the glucose mooi-
`60 toring device to optically detect the color change.
`Alternatively, electrochemical analysis is another type of
`analysis which may be utilized in conjunction with the
`microoeedle patch 200 of present invention to determine the
`concentration of glucose in a user's blood. Io such an
`65 embodiment, the test cbamber 104 includes a pair of elec­
`trodes. In electrochemical analysis, the change in current
`across the electrodes caused by the reaction of the glucose
`
`AGAMATRIX, INC. EXHIBIT NO. 1023
`Page 13 of 15
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`US 6,603,987 B2
`
`s
`is indicative of the concentration of the
`and the reagent
`glucose in the blood. The reaction of the glucose and the
`reagent creates an oxidation current at the electrode which is
`directly proportional to the user's blood glu.cose concentra­
`
`tion. This current can be measured by an appropriate sensor 5
`
`implemented in an glucose monitoring device for use with
`the patch 200. The glucose monitoring device can then
`communicate to the user the blood glucose concentration.
`Both calorimetric and electrochemical testing systems are
`
`described in detail by commonly-owned U.S. Pat. No. 10
`
`6
`Once the requisite blood sample has been obtained and the
`requisite time bas elapsed for the reaction in the test chamber
`204 of the microneedle patch 200 to occur, the blood glucose
`monitoring system 350 determines the blood glucose con­
`centration and communicates tl1e result to tl1e user via a
`display 356. The used microneedle array patch is then
`ejected from the system 350. Both electrochemical sensing
`and colorimetric sensing as well as other types of blood
`glucose analysis may be implemented within the blood
`glucose monitoring system 350 of the present invention.
`Referring now to FIG. 12, another alternative embodi­
`ment of the present invention is illustrated wherein the
`microneedle patch 200 bas an adhesive 360 disposed on an
`upper surface 362 of the microneedle patch 200 in an
`another alternative embodiment of the present invention.
`The adhesive 360 bolds the microneedle patch 200 against
`a user's skin 206. The adhesive 360 is useful in an embodi­
`ment o( tbe microneedle patcb 200 wherein a longer period
`of time is requjred for the harvesting of the blood sample and
`then the occurrence of tl1e reaction between the glucose in
`the blood and the reagent disposed in the test chamber 204.
`Also illustrated in FIG. 12 are tbe pair of electrodes 353
`disposed in the test chamber 203.
`While the invention is susceptible to various modifica­
`tions and alternative forms, specific embodiments thereof
`have been shown by way of example in the drawings and
`will be described in detail herein. It should be understood,
`however, that it is not intended to limit the invention to the
`particular forms disclosed, but, to the contrary, tbe intention
`is to cover all modifications, equivalents and alternatives
`falling wit bin the spirit and scope of the invention as defined
`by the appended claims.
`What is claimed is:
`1. A test strip for use in the determination of the concen­
`tration of an a chemical in blood, comprising:
`a plurality of microneedles, each microneedle being
`adapted to puncture skin and to draw blood, each
`microneedle baving a generally cylindrical wall and a
`collection point, the collection point being adapted to
`receive blood and to direct blood to the test area, the
`cylindrical wall at the collection point being upwardly
`sloping in a direction moving radially away from the
`center of tbe microneedle; and
`a test area in fluid communication with the microneedles,
`the test area containing a reagent being adapted to
`produce a reaction indicative of the concentration of a
`chemical in blood.
`2. The test strip of claim 1 wherein the reagent is adapted
`to produce a colorimetric reaction.
`3. The test strip of claim 2 in combination with a colo­
`rimetric sensor.
`4. The test strip of claim 1 wherein the reagent is adapted
`to produce an electrochemical reaction, the test strip further
`comprising a pair of electrodes coupled to the test area.
`5. The test strip of claim 4 in combination with a sensor
`being adapted to measure a change in current across tbe
`electrodes.
`6. The test strip of claim 1 wherein the chemical is
`glucose.
`7. The test strip of claim 6 in combination with a sensor
`adapted to measure the concentration of glucose in tbe
`blood.
`8. The test strip of claim 1 further comprising an adhesive
`disposed on the test area, the adhesive being adapted to
`65 adhere the test strip to skin.
`9. The test strip of claim 1 wherein each microneedle bas
`a length of at least about 0.005 inch.
`
`5,723,284 entitled "Control Solution and Method for Testing
`the Performance of an Electrochemical Device for Deter­
`mining the Concentration of an Analyte in Blood" which is
`incorporated herein by reference in its entirety.
`
`Referring now to FIG. 9, a glucose monitoring device 300 15
`
`bav ing a calorimetric sensor (a spectrophotometric
`instrument) 302 which may used in conjunction with the
`microneedle array patcb 200 is illustrated. Tbe test chamber
`204 of the microneedle array patcb 200 contains appropriate
`
`reagents designed to react with glucose in a manner to 20
`
`produce a change in color indicative of the glucose concen­
`tration in the user's blood. The glucose monitoring device
`300 having a colorimetric sensor 302 determines the glucose
`concentration and informs the user of tbe result. Tbe moni­
`
`toring device 300 is activated with a switch 304. After the 25
`
`microneedle array patch 200 is pressed onto the user's skin
`and the requisite amount of time bas past for the reaction to
`occur, the monitoring device 300 is brought into close
`proximity to tbe microneedle array patch 200 to read the
`colorimetric signal produced by the reaction. Tbe test cham- 30
`ber 204 bas a transparent back cover 218 allowing the
`calorimetric sensor 302 in the monitoring device 300 to
`optically read the signal. Tbe monitoring then determines the
`blood glucose concentration and communicates those resulls
`to the user via a display 306. The microneedle patch 200 can 35
`then be removed and discarded.
`Alternatively, electrochemical sensing can be employed
`in conjunction witl1 the micro needle array path of tbe present
`invention. FIG. 10 illustrates a suitable monitoring device
`320 which can be used in conjunction with an embodiment 40
`of the microneedle patch 200 designed for electrochemical
`sensing. Tbe embodiment of the microneedle patch 200
`designed for electrochemical sensing contains a pair of
`electrodes 353. The blood glucose monitoring device 320
`contains a pair of corresponding electrodes 352 (shown in 45
`FIG. 10). Tbe blood glucose monitoring device 350 is
`activated witb a switcb 354. Once tbe microneedle patch 200
`is pressed onto a users skin and a requisite amount o( time
`has passed for the electrochemical reaction to occur, the
`electrodes 352 of the monitoring device are bought into 50
`contact with the corresponding electrodes 353 on the
`microneedle patch 200. The results of the blood glucose
`analysis are communicated to the user via a display 356.
`Referring now to FIG. 11, another application of the
`microneedle patch 200 of the present invention is in an 55
`integrated blood glucose monitoring system 350 which
`integrates the microneedle array patch 200 and a blood
`glucose analyzer into a single instrument. The integrated
`blood glucose monitoring system contains a plurality of
`microneedle patches 200 and when activated moves a new 60
`microneedle patch 200 to tbe test end 352 of tbe system 350.
`Jn operation, a user would activate the system 350 with a
`switch 354. A new microneedle patch 200 is advanced to the
`test end 352 of the system 350. The user would then press
`the test end 352 of the system against the user's skin causing
`each of the microneedles 202 in tbe array of microneedles
`202 to lance the user's skin and to harvest the blood sample.
`
`AGAMATRIX, INC. EXHIBIT NO. 1023
`Page 14 of 15
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`US 6,603,987 B2
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`8
`13. The system of claim 12 wherein the reagent is adapted
`to produce a colorimetric reaction and the sensor is a
`colorimetric sensor.
`14. The system of claim 12 wherein the bottom of the test
`
`5 chamber is transparent.
`
`7
`10. The test strip of claim 1 wherein each microneedle is
`hollow.
`11. The test strip of claim 1 wherein the plurality of
`microneedles is a twenty by twenty microneedle array.
`12. A blood chemical monitoring system for monitoring
`the concentration of chemical in blood, the system compris­
`ing:
`a test chamber having a top and a bottom, the test chamber
`containing a reagent;
`an array of hollow microoeedles, each of the hollow
`microneedles being adapted to draw blood, each of the
`microneedles containing an inlet and an outlet, said
`inlet being adapted to puncture skin, the outlet being in
`fluid communication with the test chamber, each
`microneedle having a generally cylindrical wall, the
`cylindrical wall at the inlet being upwardly sloping in
`a direction moving radially away from the center of the
`microoeedle at the collection point; and
`a sensor for determining the concentration of a chemical
`in the blood.
`
`10
`
`15. The system of claim 12 wherein the test chamber
`includes a pair of electrodes and the reagent is adapted to
`produce an electrochemical reaction, the sensor being
`adapted to measure a change in current across the electrodes.
`16. The system of claim 12 wherein the chemical is
`glucose.
`17. The system of claim U futher comprising an adhesive
`disposed on the top of the test chamber, the adhesive being
`adapted to adhere the test chamber to skin.
`18. The system of claim 12 wherein each hollow micron-
`
`15 eedle bas a length of at least about 0.005 inch.
`
`19. The system of claim 12 wherein the array of hollow
`microoeedles is a twenty by twenty hollow microneedle
`array.
`
`* * * * *
`
`AGAMATRIX, INC. EXHIBIT NO. 1023
`Page 15 of 15
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