`
`US 7,043,287 B1
`(10) Patent No.:
`(12) United States Patent
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Khalil et a].
`(45) Date of Patent:
`May 9, 2006
`
`
`
`USOO7043287B1
`
`
`
`(54) METHOD FOR MODULATING LIGHT
`
`
`
`
`
`PENETRATION DEPTH IN TISSUE AND
`
`
`
`
`DIAGNOSTIC APPLICATIONS USING SAME
`
`
`
`
`
`
`(75)
`
`
`
`
`
`
`Inventors: Omar S. Khalil, Libertyville, IL (US);
`
`
`
`
`
`Shu-Jen Yeh, Grayslake, IL (US);
`.
`.
`
`X‘aofna" W“: Gumees IL (Us):
`
`
`
`
`
`
`
`
`Stanislaw Kantor, Buifalo Grove, IL
`(US); Charles F. Hanna, LibertyVille,
`
`
`
`
`IL (US); szy-Wen Jeng, Vernon Hills,
`
`
`
`
`
`IL (US)
`
`
`
`
`
`
`
`(73) Assignee: Abbott Laboratories, Abbott Park, IL
`
`
`
`
`
`
`
`
`(US)
`
`
`( * ) Notice:
`
`
`
`
`
`
`
`
`
`Subject to any disclaimer, the term of this
`
`
`
`
`patent is extended or adjusted under 35
`
`
`
`
`U~S~C~ 154(b) by 0 days'
`
`
`
`
`(21) APP1~ N05 09/412461
`.
`
`Flledi
`
`(22)
`
`
`
`
`Oct-15, 1999
`
`
`
`
`
`
`Related US. Application Data
`
`
`
`
`
`
`
`
`
`
`(63) Continuation-in-part of application No. 09/302,207,
`filed onApr. 29, 1999, HOW Pat. NO. 6,241,663, Wthh
`
`
`
`
`
`
`
`is a continuation-in-part of application No. 09/080,
`
`
`
`
`
`
`470, filed on May 18, 1998, now Pat. No. 6,662,030.
`
`
`
`
`
`
`
`
`
`(51)
`
`
`Int. Cl.
`
`
`(2006.01)
`A613 5/00
`
`
`
`....................................... 600/310; 600/316
`(52) US. Cl.
`
`
`
`
`
`(58) Field of Classification Search ........ 600/31(L311,
`
`
`
`
`
`
`
`
`
`
`
`
`
`600/316, 3227324, 326, 328, 334, 339; 356/39741
`See application file for complete search history.
`
`
`
`
`
`
`
`
`(56)
`
`
`References Cited
`
`
`
`
`U'S' PATENT DOCUMENTS
`
`
`
`12/1971 Polanyi et 31.
`3,628,525 A
`
`
`
`
`3,638,640 A
`2/1972 Shaw
`
`
`
`4,223,680 A
`9/1980 Jobsis
`
`
`
`4,259,963 A
`4/1981 Huch
`
`
`
`4,432,365 A
`2/1984 Leist
`
`
`
`
`4,655,225 A
`
`4,882,492 A
`
`4,890,619 A
`
`4,926,867 A
`
`
`4975581 A
`
`5,007,423 A
`5,057,695 A
`
`5,086,229 A
`
`
`5,115,133 A
`5,122,974 A
`
`5,131,391 A
`
`5,148,082 A
`
`5,187,672 A
`
`5,209,231 A
`
`
`5,218,207 A
`5,237,178 A
`
`
`5’277’181 A
`
`5’284’139 A
`5,297,548 A
`
`
`5,313,941 A
`5,321,265 A
`
`
`5,324,979 A
`5,337,745 A
`
`5,348,002 A
`
`5,348,003 A
`
`5,361,758 A
`
`
`5:372:72: :
`5,379,764 A
`
`5,383,452 A
`
`5,402,778 A
`
`5,452,716 A
`
`5,481,113 A
`
`5,492,118 A
`
`5492769 A *
`
`2mg: 2
`
`
`5,515,847 A
`5,533,509 A
`
`5,551,422 A
`
`5,553,615 A
`
`5,553,616 A
`
`5,596,987 A
`
`5,665,530 A
`
`5,672,875 A
`
`5,676,143 A
`
`5,720,284 A
`
`5,725,480 A
`
`5,755,226 A
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`4/1987 Dahne et al.
`
`
`11/1989 Schlager
`
`
`1/ 1990 Hatschek
`
`
`5/1990 Kanda et al.
`
`
`
`
`
`
`”“990 RObmson et 31'
`
`
`4/1991 Branstetter et al.
`10/1991 Hirao et al.
`
`
`
`2/1992 Rosenthal et a1.
`
`
`
`
`
`5/1992 Knudson
`6/1992 Chance
`
`
`7/1992 Sakai et a1.
`
`
`9/1992 Itou et 31.
`
`
`
`2/1993 Chance et al.
`
`
`5/ 1993 Cote 6t al~
`
`
`
`
`
`6/1993 Rosenthal
`8/1993 Rosenthal et al.
`
`
`
`
`
`
`“994 Mendelson et 31'
`
`
`
`2/1994 Khahl et 31'
`3/1994 Pologe
`
`
`
`
`
`5/1994 Braig et a1.
`6/1994 Block
`
`
`
`6/1994 Rosenthal
`8/1994 Benaron
`
`
`9/1994 Caro
`
`
`9/1994 Caro
`
`
`11/1994 Hall et a1.
`
`
`
`
`i533:
`ISiZZZIifléétfla? 31'
`1/1995 Barnes Ct 211.
`
`
`
`1/1995 Buchert
`
`
`4/1995 Chance
`
`
`9/1995 Clift
`
`
`1/1996 Dou et 31.
`
`
`
`2/1996 Gratton et a1.
`
`
`
`/
`2;1996 Pryor 6t 3151
`
`
`
`
`
`3,1332 32:21:21 ' “““““““ 600 323
`
`
`
`
`
`5/1996 Braig et a1.
`7/1996 Koashi et 31.
`
`
`
`9/1996 Simonsen et al.
`
`
`9/1996 Carim et a1.
`
`
`
`9/1996 Ham et 31.
`
`
`
`1/1997 Chance
`
`
`9/1997 Oyamada et 31.
`
`
`9/1997 Block et 31.
`
`
`
`10/1997 Simonsen et 31.
`
`
`2/1998 Aoyagi et 31.
`
`
`
`3/1998 Oosta et 31.
`
`
`
`5/1998 Carim et al.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Page 1
`
`VALENCELL EXHIBIT 2015
`
`IPR2017-00321
`
`Page 1
`
`VALENCELL EXHIBIT 2015
`IPR2017-00321
`
`
`
`
`
`US 7,043,287 B1
`
`Page 2
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`6/1998 Essenpris et al.
`5,770,454 A
`
`
`
`
`7/1998 Chance et al.
`.............. 600/322
`5,782,755 A *
`
`
`
`
`
`10/1998 Messerschmidt
`5,823,951 A
`
`
`
`2/1999 Chance et al.
`.............. 600/310
`5,873,821 A *
`
`
`
`
`
`
`8/1999 Arakaki et al.
`..... 600/310
`.
`5,931,779 A *
`
`
`
`
`
`
`11/1999 Mills ................... 600/334
`5,978,691 A *
`
`................. 600/316
`6,161,028 A * 12/2000 Braig et al.
`
`
`
`
`
`
`................. 600/310
`6,198,949 B1 *
`3/2001 Braig et al.
`
`
`
`
`
`
`
`FOREIGN PATENT DOCUMENTS
`
`
`
`44 17 639
`11/1995
`
`
`
`3/1998
`196 34 152
`
`
`
`0 472 216
`2/1992
`
`
`
`
`12/1997
`0 810 429
`
`
`
`
`6/1992
`92/10131
`
`
`11/1992
`93/20273
`
`
`4/1993
`93/07801
`
`
`7/1993
`93/13706
`
`
`2/1994
`94/02837
`
`
`3/1994
`94/05984
`
`
`6/1994
`94/13199
`
`
`8/1995
`95/20757
`
`
`1/1998
`98/03847
`
`
`8/1999
`99/39631
`
`
`11/1999
`99/55222
`
`
`11/1999
`99/59464
`
`
`OTHER PUBLICATIONS
`
`
`Applied Optics, V01. 31, No. 10, Apr. 1, 1992.
`
`
`
`
`
`
`
`
`Bruulsema, et al., “Correlation between blood glucose con-
`
`
`
`
`
`
`
`centration in diabetics and noninvasively measured tissue
`
`
`
`
`
`
`
`optical scattering coeflicient”, Optics Letters, vol. 22, No. 3,
`
`
`
`
`
`
`
`
`1997, pp. 190-192.
`
`
`
`Heinemann, et al., “Non-invasive continuous glucose moni-
`
`
`
`
`
`
`toring in Type 1 diabetic patients with optical glucose
`
`
`
`
`
`
`
`
`sensors”, Diabetologia, vol. 41, 1998, pp. 848-854.
`
`
`
`
`
`
`
`Kienle, et al. “Spatially resolved absolute diffuse reflectance
`
`
`
`
`
`
`
`measurements for noninvasive determination of the optical
`
`
`
`
`
`
`scattering and absorption coeflicients of biological tissue”,
`
`
`
`
`
`
`
`Applied Optics, vol. 35, No. 13, 1996, pp. 2304-214.
`
`
`
`
`
`
`
`
`
`Marbach, et al., “Noninvasive Blood Glucose Assay by
`
`
`
`
`
`
`
`Near-Infrared Diffuse Reflectance Spectroscopy of the
`
`
`
`
`
`
`Human Inner Lip”, Applied Spectroscopy, vol. 47, No. 7,
`
`
`
`
`
`
`
`
`1993, pp. 875-881.
`
`
`
`Qu, et al., “Monte Carlo Modeling Studies of the Effect of
`
`
`
`
`
`
`
`
`Physiological Factors and other Analytes on the Determi-
`
`
`
`
`
`
`
`
`nation of Glucose Concentration In vivo by Near Infrared
`
`
`
`
`
`
`Optical Absorption and Scattering Measurements”, Journal
`
`
`
`
`
`
`of Biomedical Optics, vol. 2, No. 3, (1997), pp. 319-325.
`
`
`
`
`
`
`
`
`Quan,
`al.,
`“Glucose determination by a pulsed
`et
`
`
`
`
`
`
`
`photoacoustic technique: an experimental study using a
`
`
`
`
`
`
`gelatin-based tissue phantom”, Phys. Med. Biol., vol. 38
`
`
`
`
`
`
`
`
`(1993) pp. 1911-1922.
`
`
`
`Robbins, et al., “The Endocrine Pancreas”, Pathologic Basis
`
`
`
`
`
`
`
`of Disease, 3rdl Edition, W. B. Saunders Company (1984),
`
`
`
`
`
`
`
`
`pp. 972-990.
`
`
`Tooke, et al., “Skin Microvascular Blood Flow Control in
`
`
`
`
`
`
`
`Long Duration Diabetics with an without Complications”,
`
`
`
`
`
`
`Diabetes Research, No. 5, 1987, pp. 189-192.
`
`
`
`
`
`
`Wilson, et al, “Progress toward the Development of an
`
`
`
`
`
`
`
`
`Implantable Sensor for Glucose”, Clinical Chemistry, vol.
`
`
`
`
`
`
`
`38, No. 9, 1992, pp. 1613-1617.
`
`
`
`
`
`R. Graalf, et al., “Reduced light-scattered properties for
`
`
`
`
`
`
`
`
`mixtures of spherical particles: a simple approximation
`
`
`
`
`
`
`derived from Mie calculations”, Applied Optics, vol. 31, No.
`
`
`
`
`
`
`
`
`
`10, Apr. 1, 1992, pp. 1370-1376.
`
`
`
`
`
`
`DE
`
`DE
`
`EP
`
`EP
`
`WO
`
`WO
`
`WO
`
`WO
`
`WO
`
`WO
`
`WO
`
`WO
`
`WO
`
`WO
`
`WO
`
`WO
`
`
`Page 2
`
`Jobsis, “Noninvasive, Infrared Monitoring of Cerebral and
`
`
`
`
`
`
`
`
`
`
`
`
`Myocardial Oxygen Sufliciency and Circulatory Param-
`eters”, Science, vol. 198, 1977, pp. 1264-1267.
`
`
`
`
`
`
`
`Gopinath, et al., “Near-infrared spectroscopic localization of
`
`
`
`
`
`intracranial hematomas”, Journal ofNeurosurgery, vol. 79.
`
`
`
`
`
`
`1993, pp. 43-47.
`
`
`
`Zhang, et al., “Investigation of Noninvasive in Vivo Blood
`
`
`
`
`
`
`Hematocrit Measurement Using NIR Reflectance Spectros-
`
`
`
`
`
`
`copy and Partial Least-Squares Regression”, Applied Spec—
`
`
`
`
`
`
`
`troscopy, vol. 54, No. 2, 2000, pp. 294-299.
`
`
`
`
`
`
`
`Lin, et al., “Dynamics of tissue optics during laser heating
`
`
`
`
`
`
`
`
`ofturbid media”, Applied Optics, vol. 35, No. 19, 1996, pp.
`
`
`
`
`
`
`
`
`
`
`3413-3420.
`
`Laufer, et al., “Effect of temperature on the optical properties
`
`
`
`
`
`
`of ex vivo human dermis and subdermis”, Phys. Med. Biol,
`
`
`
`
`
`
`
`
`
`vol. 43, 1998, pp. 2479-2489.
`
`
`
`
`
`Bruulsema, et al., “Optical Properties of Phantoms and
`
`
`
`
`
`
`
`Tissue Measured in vivo from 09-13 pm using Spatially
`
`
`
`
`
`
`
`
`Resolved Diffuse Reflectance”, SPIE Proceedings, vol.
`
`
`
`
`
`
`2979, 1997, pp. 325-334.
`
`
`
`
`T. Shiga, et al., “Study of an Algorithm Based on Model
`
`
`
`
`
`
`
`Experiments and Diffusion Theory for a Portable Tissue
`
`
`
`
`
`
`
`Oximeter”, Journal ofBiomedical Optics, vol. 2, No. 2, Apr.
`
`
`
`
`
`
`
`1997, pp. 154-161.
`
`
`
`Jacques, et al., “Monte Carlo Modeling of Light Transport in
`
`
`
`
`
`
`
`
`
`
`
`
`Tissues”, Optical—Thermal Response of Laser—Irradiated
`Tissue, edited by A.J. Welch and M.J.C. van Gemert, Plenum
`
`
`
`
`
`
`
`
`
`Press, New York, 1995, pp. 73-100.
`
`
`
`
`
`
`Wilson, “Measurement of Tissue Optical Properties: Meth-
`
`
`
`
`
`
`ods and Theories”, Optical-Thermal Response of Laser-
`
`
`
`
`
`
`
`Irradiated Tissue, edited by A.J. Welch and M.J.C. van
`
`
`
`
`
`
`
`
`
`Gemert, Plenum Press, New York, 1995, pp. 233-274.
`
`
`
`
`
`
`
`
`Morris, et al., “Basic Examination of Blood”, Clinical
`
`
`
`
`
`
`
`
`Diagnosis and Management by Laboratory, 1996, pp. 549-
`
`
`
`
`
`
`
`559.
`
`Lin, et al., “Dynamics of tissue reflectance and transmittance
`
`
`
`
`
`
`
`during laser irradiation”, SPIE Proceedings, vol. 2134A
`
`
`
`
`
`
`
`Laser-Tissue Interaction V, 1994, pp. 296-303.
`
`
`
`
`
`PCT International Search Report.
`
`
`
`
`
`* cited by examiner
`
`
`
`
`
`Primary ExamineriEric F. Winakur
`
`
`
`(74) Attorney, Agent, or FirmiDavid L. Weinstein
`
`
`
`
`
`
`
`
`(57)
`
`
`
`ABSTRACT
`
`
`
`Devices and methods for non-invasively measuring at least
`
`
`
`
`
`
`
`one parameter of a sample, such as the presence of a disease
`
`
`
`
`
`
`
`condition, progression of a disease state, presence of an
`
`
`
`
`
`
`
`analyte, or concentration of an analyte,
`in a biological
`
`
`
`
`
`
`
`
`sample, such as, for example, a body part. In these devices
`
`
`
`
`
`
`
`
`
`and methods,
`temperature is controlled and is varied
`
`
`
`
`
`
`
`between preset boundaries. The methods and devices mea-
`
`
`
`
`
`
`
`
`sure light that is reflected, scattered, absorbed, or emitted by
`
`
`
`
`
`
`
`the sample from an average sampling depth, dav, that is
`
`
`
`
`
`
`
`
`
`confined within a region in the sample wherein temperature
`
`
`
`
`
`
`
`is controlled. According to the method of this invention, the
`
`
`
`
`
`
`
`
`sampling depth dav, in human tissue is modified by changing
`
`
`
`
`
`
`
`the temperature of the tissue. The sampling depth increases
`
`
`
`
`
`
`
`
`as the temperature is lowered below the body core tempera-
`
`
`
`
`
`
`
`
`
`ture and decreases when the temperature is raised within or
`
`
`
`
`
`
`
`above the body core temperature. Changing the temperature
`
`
`
`
`
`
`
`
`at the measurement site changes the light penetration depth
`
`
`
`
`
`
`
`
`
`in tissue and hence dav. Change in light penetration in tissue
`
`
`
`
`
`
`
`
`
`as a function of temperature can be used to estimate the
`
`
`
`
`
`
`
`
`
`Page 2
`
`
`
`
`
`US 7,043,287 B1
` Page 3
`
`
`presence of a disease condition, progression of a disease
`
`
`
`
`
`
`
`state, presence Of an analyte, or concentration Of an analyte
`
`
`
`
`
`
`
`
`
`
`
`
`in a biological sample. According to the method of this
`invention, an optical measurement is performed on a bio-
`
`
`
`
`
`
`logical sample at a first temperature. Then, when the optical
`
`
`
`
`
`
`
`
`
`
`
`
`
`measurement is repeated at a second temperature, light will
`
`is
`penetrate into the biological sample to a depth that
`
`
`
`
`
`
`
`different from the depth to which light penetrates at the first
`
`
`
`
`
`
`
`
`
`
`
`
`
`temperature by from about 5% to about 20%.
`
`
`
`
`
`
`
`30 Claims, 14 Drawing Sheets
`
`
`
`Page 3
`
`Page 3
`
`
`
`
`U.S. Patent
`
`
`
`
`
`May 9, 2006
`
`
`
`Sheet 1 of 14
`
`
`
`US 7,043,287 B1
`
`
`
`
`
`a .
`
`UHh
`
`
`
`
`
`#S:5
`
`Q,62% ”FANPAF
`
`
`
`Page 4
`
`Page 4
`
`
`
`
`tnetaP
`
`
`
`aM
`
`
`
`6002a,y
`
`41f02mhS
`
`
`
`
`
`US 7,043,287 B1
`
`N307m
`
`
`m_
`
`
`
`mJaoogmokowhmo
`
`
`
`
`
`
`
`mo<mKMHZ_ Z<§DI
`
`nu
`
`QMm_
`
`MJDQOEmomaomF:o_4
`
`
`
`
`
`MJDQOE
`
`Page 5
`
`Page 5
`
`
`
`
`
`U.S. Patent
`
`
`
`
`May 9, 2006
`
`
`
`
`
`Sheet 3 of 14
`
`
`
`US 7,043,287 B1
`
`mm.UHL
`
`
`
`
`
`
`
`
`
`
`
`
`<m.UHm
`
`
`
`
`
`
`am
`
`
`
`9
`
`
`
`mm
`
`
`
`
`
`
`
`Page 6
`
`
`
`QC.mOHUmHmDQC.ZOZZOUAHHmUmDOm
`
`Page 6
`
`
`
`
`
`U.S. Patent
`
`
`
`
`
`May 9, 2006
`
`
`Sheet 4 0f 14
`
`
`
`US 7,043,287 B1
`
`
`FIG.4-
`
`
`
`
`
`
`
`
`
`
`
`
`
`Page 7
`
`Page 7
`
`
`
`
`U.S. Patent
`
`
`
`
`
`May 9, 2006
`
`
`Sheet 5 0f 14
`
`
`
`US 7,043,287 B1
`
`(D
`v
`
`
`<0
`Fl
`
`N
`fi‘
`
`
`
`m
`‘r
`
`E
`
`
`
`‘ Y ' '4
`:2»3 0‘
`8‘ 0V
`8%.:
`
`LO
`
`
`
`
`
`U
`h—i
`ha
`
`
`
`Page 8
`
`Page 8
`
`
`
`
`U.S. Patent
`
`
`
`May 9, 2006
`
`
`
`
`Sheet 6 0f 14
`
`
`
`
`
`US 7,043,287 B1
`
`1.10
`
`1.05
`
`1.00
`
`0.95
`
`0.90
`
`035
`
`—I:1—r=0.92mm
`-—1r—r=134mm --------------
`
`
`
`
`
`
`
`
`
`
`
`
`
`ratiotofirstpoint
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`0.80
`ratiotofirstpoint
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`time, min
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`FIG. 6A
`
`Page 9
`
`Page 9
`
`
`
`
`U.S. Patent
`
`
`
`
`
`May 9, 2006
`
`Sheet 7 of 14
`
`
`
`
`US 7,043,287 B1
`
`1.2
`
`1.15
`
`
`E8;“2:20:9._
`
`1.1
`
`W2”
`
`Illlll
`Tlllulllll
`
`time, min
`
`
`
`
`1.1
`
`1 .08
`
`1 .06
`
`ion“9.:20:9.
`
`Page 10
`
`
`
`time. min
`
`
`
`
`
`FIG. 6B
`
`
`
`
`
`Page 10
`
`
`
`
`
`U.S. Patent
`
`02
`
`f08tw
`
`4
`
`US 7,043,287 B1
`
`
`
`
`
`9,Huy3835.\atv‘\.ru-M............,..........................\~..\.\...\......fi...........................n.............u............\..nt.\:4.....Q:
`
`
`
`
`
`
`
`M......................................:
`
`h:2:S..n‘
`
`12
`
`b.UHH
`
`0o6.39.252
`
`NVowmmmmvmmmonmmmm.VN
`
`
`
`
`
`Aw............W.....Wu00_fl3mpll\..mmWm.m
`
`FE33
`
`‘\
`
`mdw
`
`NF
`
`s
`
`ow.
`
`Page 11
`
`Page 11
`
`
`
`
`
`U.S. Patent
`
`
`
`
`May 9, 2006
`
`
`
`
`Sheet 9 0f 14
`
`
`
`US 7,043,287 B1
`
`
`
`‘ 0
`
`
`
`1o
`
`
`20
`
`
`
`30
`
`
`4o
`
`
`50
`
`
`time, min
`
`
`
`so
`
`
`
`70
`
`
`
`80
`
`
`
`so
`
`
`
`100
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` o
`
`7o
`
`80
`
`90
`
`100
`
`10
`
`20
`
`30
`
`4o
`
`50
`time, min
`
`60
`
`
`FIG. 8A
`
`Page 12
`
`Page 12
`
`
`
`
`U.S. Patent
`
`
`
`
`May 9, 2006
`
`
`
`
`Sheet 10 0f 14
`
`
`
`US 7,043,287 B1
`
`aoohm, 950nm;
`
`o
`
`10
`
`20
`
`30
`
`50
`4o
`time, min
`
`60
`
`7o
`
`80
`
`90
`
` 0
`
`60
`
`
`
`7o
`
`
`
`80
`
`
`
`90
`
`
`
`
`
`1o
`
`
`20
`
`
`30
`
`
`50
`4o
`
`
`
`
`time, min
`
`
`
`Page 13
`
`Page 13
`
`
`
`
`U.S. Patent
`
`
`
`
`
`May 9, 2006
`
`
`
`Sheet 11 0f 14
`
`
`
`US 7,043,287 B1
`
`
`FIG.9
`
`120
`
`0
`
`
`
`
`
`
`
`.....................................................................
`
`
`
`-9-referenceglucose
`
`
`§§
`
`009
`as;
`H
`
`60time,min
`
`
`
`220
`
`
`
`180
`
`
`.8;
`3
`
`1p/6w 'asoonlfi
`
`120
`
`100
`
`80
`
`Page 14
`
`Page 14
`
`
`
`
`U.S. Patent
`
`
`
`
`
`May 9, 2006
`
`
`Sheet 12 0f 14
`
`
`
`US 7,043,287 B1
`
`120
`
`100
`
`80
`
`
`
`FTCLIO
`
`
`
`
`
`a)a)
`
`82C
`
`o
`d)o
`
`c 9
`
`.93
`
`9 9
`
`?I
`
`
`
`
`
`
`
`
`
`x38"Cdata
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`time,mln.
`
`
`
`
`
`
`
`
`
`
`
`O
`
`O
`00
`
`O
`0
`‘—
`
`O
`N
`N
`
`O
`C
`N
`
`D
`no
`‘—
`
`O
`<0
`
`O
`V
`
`O
`N
`F‘
`
`1p/5Lu ‘asoonIB
`
`Page 15
`
`Page 15
`
`
`
`
`U.S. Patent
`
`
`
`
`May 9, 2006
`
`
`
`
`Sheet 13 0f 14
`
`
`
`US 7,043,287 B1
`
`
`
`mg/dL
`
`
`
`FIG.11
`
`
`
`
`
`
`
`
`180.
`
`glucose,
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`In
`N
`.
`
`'
`
`O
`mm '(ooe)9v—
`
`In
`1-
`.
`0
`
`
`
`'-
`'
`O
`
`045
`
`
`
`
`
`
`035
`
`03
`
`Page 16
`
`Page 16
`
`
`
`
`U.S. Patent
`
`
`
`
`
`May 9, 2006
`
`
`Sheet 14 0f 14
`
`
`
`US 7,043,287 B1
`
`FIG.12
`
`
`
`
`
`
`
`referenceglucose,mg/dL
`
`
`
`
`
`
`150200250300
`50
`
`100
`
`300
`
`
`
`250
`
`
`8
`N
`
`8
`
`100
`
`1p/6uJ ‘esoonlfi pezelnoleo
`
`Page 17
`
`Page 17
`
`
`
`
`
`US 7,043,287 B1
`
`1
`
`METHOD FOR MODULATING LIGHT
`
`
`
`
`PENETRATION DEPTH IN TISSUE AND
`
`
`
`
`DIAGNOSTIC APPLICATIONS USING SAME
`
`
`
`
`
`This invention is a continuation-in-part of US. Ser. No.
`
`
`
`
`
`
`09/080,470, filed May 18, 1998, now US. Pat. No. 6,662,
`
`
`
`
`
`
`
`
`
`030, and is a continuation-in-part of US. Ser. No. 09/302,
`
`
`
`
`
`
`
`207, filed Apr. 29, 1999, now US. Pat. No. 6,241,663.
`
`
`
`
`
`
`
`
`
`
`
`5
`
`BACKGROUND OF THE INVENTION
`
`
`
`
`10
`
`2
`
`
`
`
`
`
`
`
`
`Disease, 3’“ Edition, W.B. Saunders Company, Philadelphia,
`1984, p. 972). If uncontrolled, diabetes can result in a variety
`
`
`
`
`
`
`
`of adverse clinical manifestations,
`including retinopathy,
`
`
`
`
`
`
`atherosclerosis, microangiopathy, nephropathy, and neur-
`
`
`
`
`
`opathy. In its advanced stages, diabetes can cause blindness,
`
`
`
`
`
`
`
`coma, and ultimately death.
`
`
`
`
`Non-invasive determination of glucose has been the sub-
`
`
`
`
`
`
`
`ject of several patents. US. Pat. Nos. 5,082,787; 5,009,230;
`
`
`
`
`
`
`
`
`4,975,581; 5,379,764; 4,655,225; 5,551,422; 5,893,364;
`
`
`
`
`
`5,497,769; 5,492,118; 5,209,231; and 5,348,003 describe a
`
`
`
`
`
`
`variety of optical methods for the noninvasive determination
`
`
`
`
`
`
`
`of glucose in the human body. However, all the previously
`
`
`
`
`
`
`
`
`mentioned patents are silent as to the effect of different
`
`
`
`
`
`
`
`
`
`
`layers of skin on optical measurements, or the effect of
`
`
`
`
`
`
`
`
`
`
`temperature on light penetration through these various layers
`
`
`
`
`
`
`
`of the skin. US. Pat. No. 5,935,062 recognizes the presence
`
`
`
`
`
`
`
`
`
`of skin layers and describes means to detect diffusely
`
`
`
`
`
`
`
`
`reflected light from the dermis and avoid light interacting
`
`
`
`
`
`
`
`
`
`with the epidermis by using a black barrier on the skin to
`
`
`
`
`
`
`
`
`separate specular reflectance and reflectance from the epi-
`
`
`
`
`
`
`
`
`dermis from reflected light that penetrated to the dermis.
`
`
`
`
`
`
`
`
`However, US. Pat. No. 5,935,062 is silent as to the effect of
`
`
`
`
`
`
`
`
`temperature on light penetrating through these layers of
`
`
`
`
`
`
`
`
`skin. The effect of temperature on the scattering and absorp-
`
`
`
`
`
`
`
`tion properties of tissue has been of interest in the art.
`
`
`
`
`
`
`
`
`
`
`
`Thermal effects of laser excitation, photocoagulation, and
`
`
`
`
`
`
`
`temperature effect on skin optics have been described in the
`
`
`
`
`
`
`
`
`art. See, for example, W-C. Lin et al., “Dynamics of tissue
`
`
`
`
`
`
`
`
`
`reflectance and transmittance during laser irradiation”, SPlE
`
`
`
`
`
`
`
`Proceedings, 2134A Laser-Tissue lnteraction V (1994)
`
`
`
`
`
`2964303; and W4C. Lin, “Dynamics of tissue optics during
`
`
`
`
`
`
`
`laser heating of turbid media”, Applied Optics (1996) Vol.
`
`
`
`
`
`
`
`
`35, No. 19, 341343420; J. Laufer et al., “Effect of tempera-
`
`
`
`
`
`
`
`
`ture on the optical properties of ex vivo human dermis and
`
`
`
`
`
`
`
`
`subdermis”, Phys. Med. Biol. 43 (1998) 247942489; J. T.
`
`
`
`
`
`
`
`
`Bruulsema et al., “Optical Properties of Phantoms and
`
`
`
`
`
`
`
`Tissue Measured in vivo from 0941.3 um using Spatially
`
`
`
`
`
`
`
`Resolved Diffuse Reflectance”, SPlE Proceedings 2979
`
`
`
`
`
`
`(1997) 3254334.
`
`
`US. Pat. Nos. 3,628,525; 4,259,963; 4,432,365; 4,890,
`
`
`
`
`
`
`
`619; 4,926,867; 5,131,391; and European Patent Application
`
`
`
`
`
`
`
`EP 0472216 describe oximetry probes having heating ele-
`
`
`
`
`
`
`
`
`ments designed to be placed against a body part. US. Pat.
`
`
`
`
`
`
`
`
`
`No. 5,148,082 describes a method for increasing the blood
`
`
`
`
`
`
`
`flow in a patient’s tissue, during a photoplethsmography
`
`
`
`
`
`measurement, by heating the tissue with a semiconductor
`
`
`
`
`
`
`
`device mounted in a sensor. US. Pat. No. 5,551,422
`
`
`
`
`
`
`
`describes a glucose sensor that is brought to a specified
`
`
`
`
`
`
`temperature, preferably somewhat above normal body tem-
`
`
`
`
`
`
`
`perature, with a thermostatically controlled heating system.
`
`
`
`
`
`
`US. application Ser. No. 09/080,470, filed May 18, 1998,
`
`
`
`
`
`
`
`
`assigned to the assignee of this application, describes a
`
`
`
`
`
`
`
`non-invasive glucose sensor employing a temperature con-
`
`
`
`
`
`
`trol. One purpose of controlling the temperature is to mini-
`
`
`
`
`
`
`
`
`mize the effect of physiological variables. US. application
`
`
`
`
`
`
`
`Ser. No. 09/098,049, filed Nov. 23, 1998, assigned to the
`
`
`
`
`
`
`
`
`
`assignee of this application, describes methods for deter-
`
`
`
`
`
`
`
`
`mining optical properties of tissue having a plurality of
`
`
`
`
`
`
`
`
`layers. Both applications teach the use of temperature con-
`
`
`
`
`
`
`
`
`trolled optical element that is brought in contact with the
`
`
`
`
`
`
`
`
`skin.
`
`Although a variety of detection techniques have been
`
`
`
`
`
`
`
`disclosed in the art, there is still no commercially available
`
`
`
`
`
`
`
`
`device that provides non-invasive glucose measurements
`
`
`
`
`
`
`with an accuracy that is comparable to the current commer-
`
`
`
`
`
`
`
`cially available invasive devices. Signals obtained by prior
`
`
`
`
`
`
`
`art methods reflect the analyte information of the tissue as if
`
`
`
`
`
`
`
`
`15
`
`20
`
`
`
`
`
`35
`
`
`1. Field of the Invention
`
`
`
`
`This invention relates to devices and methods for the
`
`
`
`
`
`
`
`
`
`noninvasive determination of in vivo concentrations of
`
`
`
`
`
`
`analytes or evaluation of a disease state, and more particu-
`
`
`
`
`
`
`
`
`larly, the noninvasive determination of in vivo concentra-
`
`
`
`
`
`
`tions of analytes or evaluation of a disease state wherein
`
`
`
`
`
`
`
`
`
`temperature is controlled and varied between preset bound-
`
`
`
`
`
`
`
`aries.
`
`2. Discussion of the Art
`
`
`
`
`Non-invasive monitoring of concentrations of analytes in
`
`
`
`
`the human body by means of optical devices and optical
`
`
`
`
`
`
`
`
`methods is an important tool for clinical diagnosis. “Non-
`
`
`
`
`
`
`
`
`invasive” (alternatively referred to herein as “Nl”) monitor-
`
`
`
`
`
`
`ing techniques measure in vivo concentrations of analytes in 25
`
`
`
`
`
`
`
`the blood or in the tissue without the need for obtaining a
`
`
`
`
`
`
`
`
`
`blood sample from the human body. As used herein, a
`
`
`
`
`
`
`
`
`
`“non-invasive” technique is one that can be used without
`
`
`
`
`
`
`
`removing a sample from, or without inserting any instru-
`
`
`
`
`
`
`
`
`mentation into, the human body. The ability to determine the 30
`
`
`
`
`
`
`
`
`
`concentration of an analyte, or a disease state, in a human
`
`
`
`
`
`
`
`subject without performing an invasive procedure, such as
`
`
`
`
`
`
`removing a sample of blood or a biopsy specimen, has
`
`
`
`
`
`
`
`several advantages. These advantages include ease in per-
`
`
`
`
`
`
`
`forming the test, reduced pain and discomfort to the patient,
`
`
`
`
`
`
`
`
`
`and decreased exposure to potential biohazards. These
`
`
`
`
`
`
`
`advantages tend to promote increased frequency of testing,
`
`
`
`
`
`
`accurate monitoring and control of a disease condition, and
`
`
`
`
`
`
`
`improved patient care. Representative examples of non-
`
`
`
`
`
`
`
`invasive monitoring techniques include pulse oximetry for 40
`
`
`
`
`
`
`
`oxygen saturation (US. Pat. Nos. 3,638,640; 4,223,680;
`
`
`
`
`
`
`
`5,007,423; 5,277,181; and 5,297,548). Another example of
`
`
`
`
`
`
`a non-invasive monitoring technique is the use of laser
`
`
`
`
`
`
`
`
`Doppler flowmetry for diagnosis of circulation disorders (J.
`
`
`
`
`
`
`E. Tooke et al., “Skin Microvascular Blood Flow Control in 45
`
`
`
`
`
`
`
`
`
`Long Duration Diabetics With and Without Complications”,
`
`
`
`
`
`
`
`Diabetes Research (1987) 5, 1894192). Other examples of
`
`
`
`
`
`
`NI techniques include determination of tissue oxygenation
`
`
`
`
`
`
`(WO 92/20273), determination of hemoglobin (US. Pat.
`
`
`
`
`
`
`
`No. 5,720,284), and determination of hematocrit (US. Pat. 50
`
`
`
`
`
`
`
`Nos. 5,553,615; 5,372,136; 5,499,627; and WO 93/13706).
`
`
`
`
`
`
`Determination of bilirubin was also described in the art (R.
`
`
`
`
`
`
`
`
`E. Schumacher, “Noninvasive Measurements of Bilirubin in
`
`
`
`
`
`the Newborn”, Clinics in Perinatology, Vol. 17, No. 2 (1990)
`
`
`
`
`
`
`
`
`4174435, and US. Pat. No. 5,353,790).
`
`
`
`
`
`
`Non-invasive diagnosis and monitoring of diabetes may
`
`
`
`
`
`
`be the most important non-invasive diagnostic procedure.
`
`
`
`
`
`
`
`Diabetes mellitus is a chronic disorder of carbohydrate, fat,
`
`
`
`
`
`
`and protein metabolism characterized by an absolute or
`
`
`
`
`
`
`
`
`relative insulin deficiency, hyperglycemia, and glycosuria.
`
`
`
`
`
`
`At least two major variants of the disease have been iden-
`
`
`
`
`
`
`
`
`
`
`
`tified. “Type 1” accounts for about 10% of diabetics and is
`
`
`
`
`
`
`
`
`characterized by a severe insulin deficiency resulting from a
`
`
`
`
`
`
`loss of insulin-secreting beta cells in the pancreas. The
`
`
`
`
`
`
`
`
`
`remainder of diabetic patients suffer from “Type 11”, which 65
`
`
`
`
`
`
`
`
`
`is characterized by an impaired insulin response in the
`
`
`
`
`
`
`
`
`
`peripheral tissues (Robbins, S. L. et al., Palhologic Basis of
`
`
`
`
`
`
`
`
`
`
`
`
`55
`
`
`60
`
`
`
`Page 18
`
`Page 18
`
`
`
`
`
`US 7,043,287 B1
`
`3
`
`the tissue comprised a single uniform layer that has a single
`
`
`
`
`
`
`
`
`
`uniform temperature. As a result, current approaches to
`
`
`
`
`
`
`non-invasive metabolite testing, such as glucose monitoring,
`
`
`
`
`
`
`have not achieved acceptable precision and accuracy.
`
`
`
`
`
`
`
`Thus, there is a continuing need for improved NI instru-
`
`
`
`
`
`
`
`ments and methods that are unaffected by variations in skin
`
`
`
`
`
`
`
`
`structures and layers or account for the effect of skin layers
`
`
`
`
`
`
`
`
`
`and the effect of temperature on the optical properties of
`
`
`
`
`
`
`
`
`
`
`
`
`these layers.
`SUMMARY OF THE INVENTION
`
`
`
`
`4
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`least one optical parameter of the
`(c) determining at
`
`
`
`
`
`
`
`
`the first
`temperature,
`the first
`biological sample at
`
`
`
`
`
`
`
`temperature corresponding to a first depth in the bio-
`
`
`
`
`
`
`
`
`logical sample;
`(d) changing the first temperature of the biological sample
`
`
`
`
`
`
`to at least a second temperature, the at least second
`
`
`
`
`
`
`
`temperature being within the physiological temperature
`
`
`
`
`
`range of the biological sample;
`
`
`
`
`(e) performing an optical measurement on the biological
`
`
`
`
`
`sample at the at least second temperature;
`
`
`
`
`
`(f) determining the at least one optical parameter of the
`
`
`
`
`
`
`
`biological sample at the at least second temperature, the
`
`
`
`
`
`
`at least second temperature corresponding to a second
`
`
`
`
`
`depth in the biological sample; and
`
`
`
`
`
`(g) determining the at least one parameter of the biologi-
`
`
`
`
`
`
`
`
`cal sample from the functional dependence of the at
`
`
`
`
`
`
`
`least one optical parameter on depth in the biological
`
`
`
`
`
`
`
`
`sample.
`Parameters of biological samples include, but are not limited
`
`
`
`
`
`
`
`
`to, the presence of a disease condition, the progression of a
`
`
`
`
`
`
`
`disease state, the presence of an analyte, or the concentration
`
`
`
`
`
`
`
`of an analyte.
`
`
`In another aspect, the present invention provides a method
`
`
`
`
`
`
`
`
`of measuring at least one parameter of a biological sample
`
`
`
`
`
`
`
`having a plurality of layers, the method comprising the steps
`
`
`
`
`
`
`
`
`of:
`
`(a) setting the temperature of the biological sample to a
`
`
`
`
`
`
`
`temperature,
`temperature being within the
`the first
`first
`
`
`
`
`
`
`
`
`physiological temperature range of the biological sample;
`
`
`
`
`
`
`(b) performing an optical measurement on the biological
`
`
`
`
`
`sample at the first temperature;
`
`
`
`
`(c) determining at least one optical parameter of a first
`
`
`
`
`
`
`
`layer of the biological sample, the first layer being located
`
`
`
`
`
`
`
`
`
`at a first depth of the biological sample, the first temperature
`
`
`
`
`
`
`
`
`
`corresponding to a first depth in the biological sample;
`
`
`
`
`
`
`(d) changing the temperature of the biological sample to
`
`
`
`
`
`
`
`at least a second temperature, the at least second temperature
`
`
`
`
`
`
`
`
`being within the physiological temperature range of the
`
`
`
`
`
`
`
`
`
`
`biological sample;
`(e) performing an optical measurement on the biological
`
`
`
`
`
`sample at the at least second temperature;
`
`
`
`
`
`(f) determining the at least one optical parameter at at
`
`
`
`
`
`
`
`
`least a second layer of the biological sample, the at least
`
`
`
`
`
`
`
`
`
`second layer being located at at least a second depth of the
`
`
`
`
`
`
`
`
`biological sample, the at least second temperature corre-
`
`
`
`
`
`
`
`sponding to the second depth of the biological sample; and
`
`
`
`
`
`
`
`
`(g) determining the at least one parameter of the biologi-
`
`
`
`
`
`
`
`
`cal sample from the functional dependence of the at least one
`
`
`
`
`
`
`
`optical parameter on depth in the biological sample.
`
`
`
`
`
`
`The method of this invention can be used to determine a
`
`
`
`
`
`
`
`disease state or screen a population of individuals for a
`
`
`
`
`
`
`
`
`disease state.
`
`
`light,
`is
`i.e.,
`In the preferred embodiments, radiation,
`
`
`
`
`
`
`
`
`introduced into the surface of a biological sample, such as a
`
`
`
`
`
`
`
`body part, at a light introduction site. The diffusely reflected
`
`
`
`
`
`
`
`
`light collected at one or more light collection sites located on
`
`
`
`
`
`
`
`
`the surface of the sample at different distances, r, from the
`
`
`
`
`
`
`
`
`light introduction site is measured. For a given light collec-
`
`
`
`
`
`
`
`
`tion site at a specific distance r from the light introduction
`
`
`
`
`
`
`
`
`
`site (sampling distance), the average light penetration depth
`
`
`
`
`
`
`
`
`in the biological sample varies with temperature. Light
`
`
`
`
`
`
`
`
`penetrates deeper into the biological sample as temperature
`
`
`
`
`
`
`
`is lowered below the body core temperature.
`
`
`
`
`
`
`
`This invention involves increasing the penetration depth
`
`
`
`
`
`
`
`of radiation, i.e., light, into a biological sample by decreas-
`
`
`
`
`
`
`
`
`ing the temperature of the biological sample below the body
`
`
`
`
`
`
`
`
`
`10
`
`15
`
`20
`
`25
`
`30
`
`
`
`
`
`35
`
`
`40
`
`45
`
`
`
`
`
`55
`
`
`60
`
`
`
`65
`
`
`This invention provides devices and methods for non-
`
`
`
`
`
`
`
`
`invasively measuring at least one parameter of a sample,
`
`
`
`
`
`
`
`such as the presence of a disease condition, progression of
`
`
`
`
`
`
`a disease state, presence of an analyte, or concentration of an
`
`
`
`
`
`
`analyte, in a biological sample, such as, for example, a body
`
`
`
`
`
`
`
`part. In these devices and methods, temperature is controlled
`
`
`
`
`
`
`
`and is varied between preset boundaries.
`
`
`
`
`
`The methods and devices of the present invention mea-
`
`
`
`
`
`
`
`
`
`sure light that is reflected, scattered, absorbed, or emitted by
`
`
`
`
`
`
`
`the sample from an average sampling depth, dav, that is
`
`
`
`
`
`
`
`
`confined within a region in the sample wherein temperature
`
`
`
`
`
`
`
`is controlled. According to the method of this invention, the
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`sampling depth dav, in human tissue is modified by changing
`the temperature of the tissue. The sampling depth increases
`
`
`
`
`
`
`
`
`as the temperature is lowered below the body core tempera-
`
`
`
`
`
`
`
`
`
`ture and decreases when the temperature is raised within or
`
`
`
`
`
`
`
`above the body core temperature. As used herein, the phrase
`
`
`
`
`
`
`
`
`
`“body core temperature” means the temperature of the
`
`
`
`
`
`
`
`
`interior of the body remote from the extremities of the body.
`
`
`
`
`
`
`Rectal temperature and esophageal temperature represent
`
`
`
`
`
`
`body core temperature. For normal human beings, body core
`
`
`
`
`
`
`
`
`
`temperature is 3711° C. Changing the temperature at the
`
`
`
`
`
`
`measurement site changes the light penetration depth in
`
`
`
`
`
`
`
`tissue and hence dav. Change in light penetration in tissue as
`
`
`
`
`
`
`
`
`a function of temperature can be used to estimate the
`
`
`
`
`
`
`
`
`
`presence of a disease condition, progression of a disease
`
`
`
`
`
`
`
`state, p