WO2001060248A1 - Non-invasive tissue glucose level monitoring - Google Patents
Non-invasive tissue glucose level monitoring Download PDFInfo
- Publication number
- WO2001060248A1 WO2001060248A1 PCT/US2001/005323 US0105323W WO0160248A1 WO 2001060248 A1 WO2001060248 A1 WO 2001060248A1 US 0105323 W US0105323 W US 0105323W WO 0160248 A1 WO0160248 A1 WO 0160248A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- radiation
- instrument
- tissue
- target
- glucose
- Prior art date
Links
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 title claims abstract description 238
- 239000008103 glucose Substances 0.000 title claims abstract description 238
- 238000012544 monitoring process Methods 0.000 title claims abstract description 43
- 238000000034 method Methods 0.000 claims abstract description 94
- 239000012491 analyte Substances 0.000 claims abstract description 23
- 230000005855 radiation Effects 0.000 claims description 249
- 210000001519 tissue Anatomy 0.000 claims description 155
- 230000005284 excitation Effects 0.000 claims description 75
- 230000001413 cellular effect Effects 0.000 claims description 71
- 239000011159 matrix material Substances 0.000 claims description 69
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 claims description 52
- 102000008186 Collagen Human genes 0.000 claims description 50
- 108010035532 Collagen Proteins 0.000 claims description 50
- 229920001436 collagen Polymers 0.000 claims description 50
- 210000004369 blood Anatomy 0.000 claims description 44
- 239000008280 blood Substances 0.000 claims description 44
- 206010012601 diabetes mellitus Diseases 0.000 claims description 42
- 230000002438 mitochondrial effect Effects 0.000 claims description 40
- 230000008859 change Effects 0.000 claims description 34
- 230000002503 metabolic effect Effects 0.000 claims description 33
- 102000004877 Insulin Human genes 0.000 claims description 26
- 108090001061 Insulin Proteins 0.000 claims description 26
- 229940125396 insulin Drugs 0.000 claims description 26
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 claims description 25
- 238000002835 absorbance Methods 0.000 claims description 23
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 claims description 21
- 239000000523 sample Substances 0.000 claims description 21
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 claims description 20
- BOPGDPNILDQYTO-NNYOXOHSSA-N nicotinamide-adenine dinucleotide Chemical group C1=CCC(C(=O)N)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]2[C@H]([C@@H](O)[C@@H](O2)N2C3=NC=NC(N)=C3N=C2)O)O1 BOPGDPNILDQYTO-NNYOXOHSSA-N 0.000 claims description 20
- 238000012545 processing Methods 0.000 claims description 18
- 230000003595 spectral effect Effects 0.000 claims description 17
- 239000003814 drug Substances 0.000 claims description 14
- 102000003983 Flavoproteins Human genes 0.000 claims description 13
- 108010057573 Flavoproteins Proteins 0.000 claims description 13
- 229940079593 drug Drugs 0.000 claims description 13
- 239000000835 fiber Substances 0.000 claims description 13
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 12
- 102000004169 proteins and genes Human genes 0.000 claims description 12
- 108090000623 proteins and genes Proteins 0.000 claims description 12
- 201000010099 disease Diseases 0.000 claims description 11
- 230000004044 response Effects 0.000 claims description 11
- 102000016942 Elastin Human genes 0.000 claims description 8
- 108010014258 Elastin Proteins 0.000 claims description 8
- 229920002549 elastin Polymers 0.000 claims description 8
- 230000008569 process Effects 0.000 claims description 7
- 102000057297 Pepsin A Human genes 0.000 claims description 5
- 108090000284 Pepsin A Proteins 0.000 claims description 5
- 230000006378 damage Effects 0.000 claims description 5
- 238000000491 multivariate analysis Methods 0.000 claims description 5
- 229940111202 pepsin Drugs 0.000 claims description 5
- 206010028980 Neoplasm Diseases 0.000 claims description 4
- 230000036571 hydration Effects 0.000 claims description 4
- 238000006703 hydration reaction Methods 0.000 claims description 4
- 208000015181 infectious disease Diseases 0.000 claims description 4
- 230000010412 perfusion Effects 0.000 claims description 4
- 125000000430 tryptophan group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C2=C([H])C([H])=C([H])C([H])=C12 0.000 claims description 4
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 claims description 3
- 239000000470 constituent Substances 0.000 claims description 3
- 239000013305 flexible fiber Substances 0.000 claims description 3
- 125000002791 glucosyl group Chemical group C1([C@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 claims description 3
- 230000008832 photodamage Effects 0.000 claims description 3
- 150000003431 steroids Chemical class 0.000 claims description 3
- 230000000699 topical effect Effects 0.000 claims description 3
- 201000011510 cancer Diseases 0.000 claims description 2
- 239000011521 glass Substances 0.000 claims description 2
- 210000004877 mucosa Anatomy 0.000 claims description 2
- 239000010453 quartz Substances 0.000 claims description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicon dioxide Inorganic materials O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 2
- 230000005670 electromagnetic radiation Effects 0.000 claims 1
- 238000005259 measurement Methods 0.000 abstract description 17
- 230000001105 regulatory effect Effects 0.000 abstract description 6
- 210000003491 skin Anatomy 0.000 description 71
- 210000004207 dermis Anatomy 0.000 description 17
- 241000894007 species Species 0.000 description 16
- 238000004458 analytical method Methods 0.000 description 14
- 230000000694 effects Effects 0.000 description 11
- 241000699670 Mus sp. Species 0.000 description 10
- 238000010521 absorption reaction Methods 0.000 description 10
- 238000000695 excitation spectrum Methods 0.000 description 10
- 238000001228 spectrum Methods 0.000 description 10
- 230000002596 correlated effect Effects 0.000 description 9
- 150000001875 compounds Chemical class 0.000 description 8
- 238000001727 in vivo Methods 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- 230000004075 alteration Effects 0.000 description 7
- 230000007423 decrease Effects 0.000 description 7
- 230000002500 effect on skin Effects 0.000 description 7
- 238000010791 quenching Methods 0.000 description 7
- 238000010586 diagram Methods 0.000 description 6
- 238000002189 fluorescence spectrum Methods 0.000 description 6
- 230000007246 mechanism Effects 0.000 description 6
- 230000032683 aging Effects 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 5
- 238000011156 evaluation Methods 0.000 description 5
- 230000037406 food intake Effects 0.000 description 5
- 230000000171 quenching effect Effects 0.000 description 5
- XUMBMVFBXHLACL-UHFFFAOYSA-N Melanin Chemical compound O=C1C(=O)C(C2=CNC3=C(C(C(=O)C4=C32)=O)C)=C2C4=CNC2=C1C XUMBMVFBXHLACL-UHFFFAOYSA-N 0.000 description 4
- 238000013461 design Methods 0.000 description 4
- 238000005286 illumination Methods 0.000 description 4
- 230000004060 metabolic process Effects 0.000 description 4
- 210000000056 organ Anatomy 0.000 description 4
- 230000001052 transient effect Effects 0.000 description 4
- 238000011282 treatment Methods 0.000 description 4
- 102000029816 Collagenase Human genes 0.000 description 3
- 108060005980 Collagenase Proteins 0.000 description 3
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 229960002424 collagenase Drugs 0.000 description 3
- -1 e.g. Proteins 0.000 description 3
- 210000002615 epidermis Anatomy 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 230000002218 hypoglycaemic effect Effects 0.000 description 3
- 230000001678 irradiating effect Effects 0.000 description 3
- 230000007774 longterm Effects 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 210000003470 mitochondria Anatomy 0.000 description 3
- 238000010606 normalization Methods 0.000 description 3
- 238000000985 reflectance spectrum Methods 0.000 description 3
- 230000035945 sensitivity Effects 0.000 description 3
- 230000001360 synchronised effect Effects 0.000 description 3
- 230000001960 triggered effect Effects 0.000 description 3
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 3
- 229910052724 xenon Inorganic materials 0.000 description 3
- FHNFHKCVQCLJFQ-UHFFFAOYSA-N xenon atom Chemical compound [Xe] FHNFHKCVQCLJFQ-UHFFFAOYSA-N 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 208000013016 Hypoglycemia Diseases 0.000 description 2
- YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 230000003321 amplification Effects 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 238000004891 communication Methods 0.000 description 2
- 238000012937 correction Methods 0.000 description 2
- 238000013480 data collection Methods 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 239000007933 dermal patch Substances 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 239000000975 dye Substances 0.000 description 2
- 239000003792 electrolyte Substances 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 230000003345 hyperglycaemic effect Effects 0.000 description 2
- 201000001421 hyperglycemia Diseases 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 230000010354 integration Effects 0.000 description 2
- 229960003299 ketamine Drugs 0.000 description 2
- 238000007726 management method Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 2
- 229910052753 mercury Inorganic materials 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012806 monitoring device Methods 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 230000000737 periodic effect Effects 0.000 description 2
- 230000019612 pigmentation Effects 0.000 description 2
- 239000004033 plastic Substances 0.000 description 2
- 229920003023 plastic Polymers 0.000 description 2
- 230000010287 polarization Effects 0.000 description 2
- 230000002035 prolonged effect Effects 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 230000037390 scarring Effects 0.000 description 2
- 230000001953 sensory effect Effects 0.000 description 2
- 238000004611 spectroscopical analysis Methods 0.000 description 2
- 210000000434 stratum corneum Anatomy 0.000 description 2
- 230000009897 systematic effect Effects 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 210000002700 urine Anatomy 0.000 description 2
- 230000000007 visual effect Effects 0.000 description 2
- INGWEZCOABYORO-UHFFFAOYSA-N 2-(furan-2-yl)-7-methyl-1h-1,8-naphthyridin-4-one Chemical compound N=1C2=NC(C)=CC=C2C(O)=CC=1C1=CC=CO1 INGWEZCOABYORO-UHFFFAOYSA-N 0.000 description 1
- 108010005094 Advanced Glycation End Products Proteins 0.000 description 1
- 206010003694 Atrophy Diseases 0.000 description 1
- VBOSYKZZGJGHJY-AFPNSQJFSA-N CCC[C@H]1C(C2)C2CC1 Chemical compound CCC[C@H]1C(C2)C2CC1 VBOSYKZZGJGHJY-AFPNSQJFSA-N 0.000 description 1
- 102000012432 Collagen Type V Human genes 0.000 description 1
- 108010022514 Collagen Type V Proteins 0.000 description 1
- 208000027932 Collagen disease Diseases 0.000 description 1
- YPZRHBJKEMOYQH-UYBVJOGSSA-N FADH2 Chemical compound C1=NC2=C(N)N=CN=C2N1[C@@H]([C@H](O)[C@@H]1O)O[C@@H]1COP(O)(=O)OP(O)(=O)OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C(NC(=O)NC2=O)=C2NC2=C1C=C(C)C(C)=C2 YPZRHBJKEMOYQH-UYBVJOGSSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 229920002683 Glycosaminoglycan Polymers 0.000 description 1
- 108010054147 Hemoglobins Proteins 0.000 description 1
- 102000001554 Hemoglobins Human genes 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 108010065920 Insulin Lispro Proteins 0.000 description 1
- 102000002274 Matrix Metalloproteinases Human genes 0.000 description 1
- 108010000684 Matrix Metalloproteinases Proteins 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 238000004497 NIR spectroscopy Methods 0.000 description 1
- 108010064719 Oxyhemoglobins Proteins 0.000 description 1
- 206010051246 Photodermatosis Diseases 0.000 description 1
- 206010039710 Scleroderma Diseases 0.000 description 1
- ZSJLQEPLLKMAKR-UHFFFAOYSA-N Streptozotocin Natural products O=NN(C)C(=O)NC1C(O)OC(CO)C(O)C1O ZSJLQEPLLKMAKR-UHFFFAOYSA-N 0.000 description 1
- 239000006096 absorbing agent Substances 0.000 description 1
- 238000000862 absorption spectrum Methods 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 239000002390 adhesive tape Substances 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 208000008784 apnea Diseases 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 238000000149 argon plasma sintering Methods 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 238000013528 artificial neural network Methods 0.000 description 1
- 238000003149 assay kit Methods 0.000 description 1
- 230000037444 atrophy Effects 0.000 description 1
- 238000005452 bending Methods 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 210000005068 bladder tissue Anatomy 0.000 description 1
- 210000005252 bulbus oculi Anatomy 0.000 description 1
- 230000019522 cellular metabolic process Effects 0.000 description 1
- 230000033077 cellular process Effects 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 230000000536 complexating effect Effects 0.000 description 1
- 230000000875 corresponding effect Effects 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 230000005786 degenerative changes Effects 0.000 description 1
- 108010002255 deoxyhemoglobin Proteins 0.000 description 1
- 238000009795 derivation Methods 0.000 description 1
- 230000001066 destructive effect Effects 0.000 description 1
- 239000010432 diamond Substances 0.000 description 1
- 235000001434 dietary modification Nutrition 0.000 description 1
- 230000003467 diminishing effect Effects 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 210000001508 eye Anatomy 0.000 description 1
- 210000000744 eyelid Anatomy 0.000 description 1
- 238000001917 fluorescence detection Methods 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 108010056686 glycosylated collagen Proteins 0.000 description 1
- 230000005484 gravity Effects 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 210000002216 heart Anatomy 0.000 description 1
- 238000005534 hematocrit Methods 0.000 description 1
- 229940038661 humalog Drugs 0.000 description 1
- WNRQPCUGRUFHED-DETKDSODSA-N humalog Chemical compound C([C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CS)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CO)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CS)NC(=O)[C@H](CS)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(O)=O)C1=CC=C(O)C=C1.C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CS)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CS)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 WNRQPCUGRUFHED-DETKDSODSA-N 0.000 description 1
- 238000012623 in vivo measurement Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 230000037353 metabolic pathway Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 230000006677 mitochondrial metabolism Effects 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 238000002095 near-infrared Raman spectroscopy Methods 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 206010033675 panniculitis Diseases 0.000 description 1
- AYEKKSTZQYEZPU-RYUDHWBXSA-N pentosidine Chemical compound OC(=O)[C@@H](N)CCCCN1C=CC=C2N=C(NCCC[C@H](N)C(O)=O)N=C12 AYEKKSTZQYEZPU-RYUDHWBXSA-N 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 230000008845 photoaging Effects 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 230000022558 protein metabolic process Effects 0.000 description 1
- 150000004053 quinones Chemical class 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000003252 repetitive effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000012883 sequential measurement Methods 0.000 description 1
- 230000009528 severe injury Effects 0.000 description 1
- 230000037067 skin hydration Effects 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000010183 spectrum analysis Methods 0.000 description 1
- ZSJLQEPLLKMAKR-GKHCUFPYSA-N streptozocin Chemical compound O=NN(C)C(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O ZSJLQEPLLKMAKR-GKHCUFPYSA-N 0.000 description 1
- 229960001052 streptozocin Drugs 0.000 description 1
- 230000009469 supplementation Effects 0.000 description 1
- 210000004876 tela submucosa Anatomy 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 229910052721 tungsten Inorganic materials 0.000 description 1
- 239000010937 tungsten Substances 0.000 description 1
- 208000035408 type 1 diabetes mellitus 1 Diseases 0.000 description 1
- 238000002211 ultraviolet spectrum Methods 0.000 description 1
- 238000005353 urine analysis Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
- A61B5/1455—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using optical sensors, e.g. spectral photometrical oximeters
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
- A61B5/0071—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence by measuring fluorescence emission
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
- A61B5/14532—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue for measuring glucose, e.g. by tissue impedance measurement
Definitions
- This invention relates to instruments and methods for performing non-invasive measurements of analyte concentrations and for monitoring, analyzing and regulating tissue status, such as tissue glucose levels.
- Diabetes is a chronic life threatening disease for which there is presently no cure. It is the fourth leading cause of death by disease in the United States and at least 175 million people worldwide are estimated to be diabetic. Diabetes is a disease in which the body does not properly produce or respond to insulin. The high glucose concentrations that can result from this affliction can cause severe damage to vital organs, such as the heart, eyes and kidneys.
- Type I diabetes (juvenile diabetes or insulin-dependent diabetes mellitus) is the most severe form of the disease, comprising approximately 10% of the diabetes cases in the United States. Type I diabetics must receive daily injections of insulin in order to sustain life. Type II diabetes, (adult onset diabetes or non-insulin dependent diabetes mellitus) comprises the other 90% of the diabetes cases. Type ⁇ diabetes is often manageable with dietary modifications and physical exercise, but may still require treatment with insulin or other medications. Because the management of glucose to near-normal levels can prevent the onset and the progression of complications of diabetes. Persons afflicted with either form of the disease are instructed to monitor their blood glucose concentration in order to assure that the appropriate level is achieved and maintained.
- Fluorolog In skin, important fluorophores include tryptophan-containing proteins, which fluoresces in the 350-450 nm region, and fluorophores associated with collagen cross links, skin oils, NADH, FAD, other flavoproteins, elastin, and quinones, which fluoresce in a broad region from 420 to 650 nm (J. Invest. Dermatol. 111 :776-780,
- Fluorescence has been used to predict malignancies in tissue, e.g., cervical tissue, bladder tissue, and the buccal cavity. Fluorescence of dyes (fluorescence associated with dyes that selectively bind to biological compounds) has also been used to study in vivo cellular processes.
- the invention overcomes problems and disadvantages associated with current strategies and designs and provides new instruments and methods for monitoring, analyzing and regulating in vivo glucose levels or other analyte levels in an individual.
- the invention features a non-invasive glucose monitoring instrument useful in vivo.
- the instrument comprises a radiation source, a radiation detector and a processing circuit or analyzing means.
- the radiation source is capable of directing excitation radiation to a portion of a tissue surface of a patient and emits radiation at least one wavelength that excites a target in the tissue to emit radiation.
- the tissue surface may be an exterior or interior tissue surface of a patient.
- the surface may be a mucosal area, such as the gums and other mucosal areas, the eyeballs, and surrounding areas, such as the eyelids. More preferably, the surface is the patient's skin.
- the tissue surface may be an interior surface such as the serosal or mucosal surface of an organ.
- the excited target provides information that can be correlated with the patient's glucose level. More specifically, the radiation emitted from the excited target and received at the tissue surface correlates with the glucose level of the tissue and thus provides a glucose level indication of the patient.
- a glucose level indication is a quantitative, qualitative or relative measurement that correlates with the blood glucose content or concentration of the patient.
- the radiation detector is positioned to receive the radiation emitted from the tissue surface. Radiation received at the surface may be quenched or amplified by one or more matrix, cellular, or mitochondrial components, or any other cellular component reflective of metabolic activity, in the tissue.
- a processing circuit is operatively connected to the radiation detector that translates emitted radiation to a measurable signal to obtain the glucose level indication.
- analyzing means is operatively connected to the radiation detector for analyzing radiation detected by the radiation detector and translating the detected radiation to an indication of the tissue glucose level.
- the excited target is not glucose itself, but a molecular component of the patient such as, for example, a component of skin or other tissue, that is related, is sensitive to, or co-varies with glucose concentration, such as tryptophan, elastin, collagen or collagen cross links, NADH, or FAD.
- Suitable targets are structural components, and compounds and molecules that reflect alterations in the environment of matrix, cellular, or mitochondrial components, or any other cellular component reflective of metabolic activity, of the tissue and are sensitive to or correlate with tissue glucose concentration.
- the target may provide an emitted fluorescence signal that is related to the patient's blood glucose level, and/or absorb certain portions of the returned signal creating a unique signal correlatable with glucose concentration, or a combination of the two.
- the radiation detector is responsive to the emission band of the target or species in the skin.
- the excitation radiation is ultraviolet radiation or visible light, such as blue light.
- the radiation emitted at the tissue surface is preferably fluorescence radiation from the excitation of the non-glucose target.
- the instrument may further include means for measuring scattering re-emitted or scattered radiation remitted from the irradiated skin and means for measuring absorbance, such as absorption from skin chromophores, like oxy- and/or deoxyhemoglobin, and melanin.
- absorbance such as absorption from skin chromophores, like oxy- and/or deoxyhemoglobin, and melanin.
- Another embodiment of the invention is directed to a non-invasive analyte monitoring instrument comprising a radiation source for directing excitation radiation to a portion of a tissue surface, (i.e., about 0.5 to 4 square centimeters of skin), a radiation detector, and a processing circuit.
- a radiation source for directing excitation radiation to a portion of a tissue surface, (i.e., about 0.5 to 4 square centimeters of skin), a radiation detector, and a processing circuit.
- the analyte being "detected” maybe correlated with glucose.
- the radiation source is a visible light source or an ultraviolet light source that emits excitation radiation at least one wavelength that excites a target in the tissue.
- the excited target emits radiation that correlates with the analyte level of the tissue or blood.
- the amount of fluorescence can reflect the quantity of a matrix, cellular or mitochondrial component that is related to the blood glucose level of the blood.
- the radiation from the excited target and received at the tissue surface may be affected by factors such as absorption, scattering, emperature, quenching, polarization, and remission of fluorescence.
- radiation received at the surface may be quenched or amplified by one or more matrix, cellular, or mitochondrial components, or any other cellular component reflective of metabolic activity, in the tissue.
- the radiation detector is positioned to receive radiation emitted from the surface of the tissue. The radiation received at the surface of the tissue provides an indication of the analyte level of the patient.
- the processing circuit is operatively connected to the radiation detector and translates emitted radiation to a measurable signal to obtain an indication of the analyte concentration or trend in the change of concentration (collectively the analyte level).
- Another embodiment is directed to a non-invasive method of detecting a glucose level of a tissue comprising: exciting a non-glucose target in the tissue wherein the target emits radiation such that the radiation received at the tissue surface is indicative of a glucose level of a patient; detecting radiation emitted by the target and transmitted through the intervening tissue to the surface; and determining the glucose level or trend in glucose levels from the radiation detected.
- the excitation radiation is ultraviolet or visible light.
- Preferred targets for monitoring or detecting glucose are non-glucose molecular species in the skin such as tryptophan-containing proteins or a matrix target, like PDCCL (pepsin digestible collagen cross links) and non-pepsin digestible collagen cross links, elastin, or other matrix and non-matrix tissue components, such as cellular or mitochondrial, NADH, pentosidine, flavoproteins, FAD, and the like.
- Targets useful for detecting analytes are excited by ultraviolet or visible radiation and act as bioamplifiers or bioreporters.
- Targets may be structural matrix, cellular, mitochondrial, or other tissue components.
- Suitable targets reflect alterations within the environment of matrix and/or tissue components of the skin or other tissue with either creation of compounds that fluoresce or causing an extant compound to fluoresce and may act as bioamplifiers or bioreporters when excited with ultraviolet radiation. Alternately, quenchers, absorbers, or scatterers may be what are acting to amplify or report. Other targets may reflect changes in redox rates of analyte transport in the tissue.
- Another embodiment is directed to a method for detecting diabetes in a patient comprising: exciting a non-glucose target using ultraviolet or visible radiation wherein the collection of light from the excited target is indicative of a glucose level or state of diabetes of a patient; detecting radiation emitted by the target; determining the glucose level from the radiation detected; and detecting diabetes based on the determined glucose level or other information.
- Another embodiment is directed to an instrument for assessing changes in the structural matrix, cellular, or mitochondrial components, or any other cellular component reflective of metabolic activity, of the skin of a patient comprising means for measuring fluorescence emitted from the skin, means for measuring scattering, and means for measuring absorbance.
- This embodiment may further include means for irradiating the tissue with a plurality of wavelengths of excitation light and means for synchronously scanning the fluorescence emitted from the skin with the excitation light.
- Another embodiment is directed to an instrument in which fluorescence measurements of matrix, cellular, or other components are reflective of the onset or state of diabetes.
- Another embodiment is directed to a method in which fluorescence measurements of matrix, cellular, or other components is reflective of the onset or state of diabetes.
- Another embodiment is directed to an instrument for assessing changes in the environment of the matrix, cellular, or mitochondrial components, or other cellular components reflective of metabolic activity, of the skin or other tissue of a patient comprising: means for measuring fluorescence; means for measuring scattering; and means for measuring absorbance.
- Preferred embodiments further include means for combining signals from the means for measuring scattering and means for measuring absorbance in visible, UV, or infrared regions with fluorescence measurements.
- Still another aspect of the invention relates to a non-invasive method of assessing a change in the superficial structural matrix, cellular, or mitochondrial components, or any other cellular component reflective of metabolic activity, of a tissue, or a change in the environment of matrix, cellular, mitochondrial, or other components reflective of metabolic activity, comprising exposing the tissue to radiation at a first wavelength, detecting fluorescence emitted by exposed tissue, exposing the tissue to radiation of a second wavelength, detecting scattering re-emitted from the exposed tissue, and deriving an indication representative of the change in the structural matrix, cellular or mitochondrial components of the tissue, or a change in tissue matrix, cellular, or mitochondrial components, or other cellular components reflective of metabolic activity, or their environment, based on fluorescence, absorbance and scattering detected.
- the method may further comprise the step of detecting absorbance.
- Another embodiment is directed to a non-invasive method for monitoring skin or tissue constituents in which information about or signature of a specific blood analyte level or disease process is provided comprising the steps of: exciting a target fluorophore; detecting radiation emitted by the fluorophore and transmitted through intervening tissue to the surface; and determining the information or signature from the radiation detected.
- multiple excitation and emission wavelengths may be used in the various embodiments without departing from the spirit and scope of the invention.
- multiple excitation wavelengths may be used while doing emission scans.
- multiple emission wavelengths can be evaluated while doing excitation scans.
- Figure 1 A multipurpose skin spectrometer that provides data specifically relevant to signals correlating with blood glucose.
- Figure 2 Block diagram of one embodiment of a glucose level monitoring instrument.
- FIG. 3 Graph of the average fluorescence excitation spectra for normal and diabetic SKH mice for an emission wavelength of 380 nm.
- Figure 4 Graph of the average fluorescence excitation spectra for normal and diabetic SKH mice for an emission wavelength of 340 nm.
- Figure 5 Graph of the average fluorescence excitation spectra for a rat at an emission wavelength of 380 nm taken at different blood glucose levels.
- Figure 6 Plot of the fluorescence intensity at 346 nm for four different glucose levels which are taken from Figure 5.
- Figure 7 Graph of the average fluorescence excitation spectra for an emission wavelength of 380 nm for a human male before and after the ingestion of 100 grams of glucose.
- Figure 8 Graph of the average fluorescence excitation spectra for an emission wavelength of 380 nm for a human male before and after the ingestion of 100 grams of glucose.
- Figure 9 Graph of the average fluorescence excitation spectra for an emission wavelength of 380 nm for a human female before and after the ingestion of 100 grams of glucose.
- Figure 10A A diagram depicting collection of fluorescence spectra with components attributable to tryptophan-containing proteins and collagen cross links following irradiation with UV light.
- Figure 10B A diagram depicting scattering according to a scattering model.
- Figure 11 Block diagram of a monitoring instrument that can be used to monitor tissue glucose levels or evaluate changes in the structural, or the environment of, matrix, cellular, or mitochondrial components, or other cellular components reflective of metabolic activity, of a tissue.
- the present invention relates to devices and methods for quantitating, trending and/or reporting an analyte, such as blood glucose, to devices and methods for monitoring and regulating in vivo glucose levels, and to devices and methods for evaluating the structural matrix, cellular, or mitochondrial components, or other cellular components reflective of metabolic activity, of a tissue.
- analyte such as blood glucose
- the glucose level of a patient can be evaluated. It has been discovered that by measuring fluorescence following irradiation of a tissue surface of a patient, such as the patient's skin, and by optionally assessing scattering and absorbance, the glucose level of a patient can be evaluated. It has been discovered that the fluorescence of a responsive target within the skin or the quantity of such a compound, which may be affected by components in the matrix, cellular, or mitochondrial, which influence the signal by amplification or quenching, is transiently affected by the radiation and can be correlated to the ambient glucose content.
- IV collagen, and other targets has previously gone unnoticed. More specifically, although glucose itself does not fluoresce to any significant degree, when the blood glucose level of a patient changes, the observable quantum efficiency of fluorescence of a target such as, for example, pepsin-digestible collagen cross links (PDCCL), also changes other mechanism. Alternatively, in processes, e.g., metabolism, that have equilibria of fluorescent molecules that are influenced by glucose concentrations, the number of fluorescent molecules present in the tissues and thus the fluorescence of the tissue will change with the patient's glucose concentration.
- a target such as, for example, pepsin-digestible collagen cross links (PDCCL)
- This change may be due, in part, to the direct and indirect effects of the relative presence of glucose or other molecules on the environment of target molecules and structures or the influence of glucose on equilibria of metabolic pathways containing fluorescent molecules. That presence may induce a reversible change in the observable quantum efficiency of fluorescence production by the target which can be detected and analyzed.
- Glucose molecules in the environment may be covalently or noncovalently coupled to the target (glycosylated collagen), free in the immediate vicinity of the target, or in the process of metabolism lead to the creation of new targets.
- the number and characteristics of fluorescent molecules are created as part of metabolic process (e.g. NADH, FAD, flavoproteins, and the like).
- Amount of fluorescent targets or characteristics of these targets may change in relation to glucose.
- the fluorescence of the target may remain constant and the effects of the environment or the intervening tissue may influence the signal recorded, or both the fluorescence of the target and intervening effects may change and produce data that can be seen to co-vary with blood glucose levels.
- Targets may be in the dermal matrix, in the epidermal matrix, or in cells, mitochondria or the immediate vicinity of cells associated with the either the dermis or the epidermis.
- the invention may also be used to directly assess the amount or degree of advanced glycation end products that exist in an area of the body such as, for example, in vessels, arteries or organs.
- a fluorescent signal in the region of one demonstrated to originate from dermal collagen cross links has been identified, which signal slowly increases with aging and is also sensitive to transient exposure to ultraviolet radiation.
- PDCCL fluoresces following excitation at 335-340 nm, with the emission maximum at 390 nm (N. Kollias et al., Journal of Investigative Dermatology, 111 :776-81 1998).
- the fluorescent signal decreases monotonically with a single UV exposure, but recovers within hours. With multiple exposures, the effects appear cumulative, and recovery takes weeks.
- transient changes in the recorded signal in the spectral region characteristic of these collagen cross links can be tightly correlated with blood glucose determinations.
- targets in the environment of matrix, cellular, or mitochondrial components, or other cellular components reflective of metabolic activity, such as collagen cross links, serve as bioamplifiers or bioreporters of ambient glucose concentrations and, thus, constitute a novel and sensitive means of non-invasively assessing glucose in real time.
- the method is also unhampered by absorption from competing species in the general area.
- fluorophores there are only a few fluorophores, making signal analysis easier.
- detector sensitivity is generally excellent and instrumentation and optical components, all of which are commercially available, are potentially simpler and less expensive than those used for infrared measurements.
- the present invention detects transient changes in fluorescence spectra that correlate with short-term changes in the concentration of blood analytes, and in particular to that of glucose. These short-term transient changes in fluorescence spectra are superimposed in the same spectral region on the long-term changes associated with aging.
- fluorescence spectra in the region 270-1,100 nm correlate with blood glucose levels.
- fluorescence spectra are measured non-invasively by placing a probe on the surface of the tissue in question, irradiating the tissue with excitation radiation, and measuring the radiation which has been re-emitted by fluorescent species (fluorophores) and transmitted back through the tissue to the tissue surface, where the probe captures it and transmits it for amplification and analysis.
- fluorescent species fluorophores
- Explanations in the first category include (1) changes in the observable quantum efficiency of the fluorophore; (2) wavelength shifts of the fluorophore in either excitation or emission space or both; or (3) quenching by some mechanism other than reducing quantum efficiency (e.g., fluorescence lifetime changes, complexing, self-quenching, or some other competing mode of relaxation which does not fluoresce.)
- Explanations in the second category include (1) creation of a new fluorophore, such as NADH from NAD; 2) degradation of an extant fluorophore, such as FAD from FADH; and 3) reflection of cellular or mitochondrial metabolism as ratios of fluorescent and non- fluorescent compounds.
- Explanations in the third category include (1) alterations in the tissue scattering length and/or scattering isotropy, resulting in alteration of the emitted radiation reaching the surface of the tissue, or (2) changes in tissue absorption related to glucose, or (3) a combination of the previous two.
- the fluorophore of interest (collagen, e.g., type V collagen, tryptophan, NADH, etc.) may be acting as an unchanging endogenous emitter, and apparent changes in the observed spectrum at the tissue surface are caused instead by the tissue scattering and absorption properties.
- Tissue absorption and scattering may affect the fluorescent signal, both by attenuating or altering the incoming excitation radiation and by attenuating or altering the outgoing fluorescent emission radiation. This attenuation or alteration may be wavelength dependent and can either increase or decrease the fluorescence emission detected.
- one aspect of the present invention is related to a non-invasive in vivo glucose monitoring instrument that determines glucose concentration, changes in glucose concentration or trends in those changes (together collectively referred to as level), by measuring fluorescence of the skin following excitation of a target or species in the skin.
- fluorescence signals obtained following irradiation of skin or other tissue can be correlated with glucose levels, or changes in glucose levels, by measuring fluorescence following excitation of targets or species within the environment of the matrix, cellular, or mitochondrial components, or other cellular components reflective of metabolic activity.
- Preferred targets are structural matrix, cellular, or mitochondrial components, or other cellular components reflective of metabolic activity, such as PDCCL.
- Another preferred target is epidermal tryptophan which, like other targets, may be bound to other compounds or structures, and intra cellularly or extracelluarly localized.
- Other useful matrix targets for excitation include collagenase-digestible cross links, elastin cross links, glycosaminoglycans, glycated collagen and glycosylated substances in a tissue.
- These targets may also be referred to as biosensors, as they are biological substances that detectably change in response to glucose content, or bioamplifiers, as they may amplify a signal indicative of systemic glucose levels.
- Another preferred target is NADH. The production of this molecule may reflect the metabolic state of the dermal or epidermal tissue, mitochondria, and/or cells.
- a non-invasive glucose-monitoring instrument includes a radiation source capable of directing radiation to a portion of the surface of the skin (or other tissue) of a patient.
- the source emits radiation at least one wavelength that excites a target or species in the tissue whose fluorescence can be correlated with blood glucose content, such that the radiation received at the tissue surface provides a glucose level indication of the patient.
- the target is a molecule other than glucose, and is a structural matrix component, such as, collagen cross links.
- the target may be tryptophan.
- Another preferred target is NADH, FAD, Flavoproteins.
- the ultraviolet radiation source is preferably operative to irradiate at approximately 330-345 nm, and the ultraviolet detector is sensitive to emitted wavelengths in the range of 370-410 nm, more preferably, 380-400 nm and, most preferably, 390 nm.
- another useful target whose change in emission may be detectable is tryptophan and preferably tryptophan-contain proteins.
- the ultraviolet radiation source is preferably operative to irradiate at approximately 285-305 nm, more preferably at approximately 295 nm, and the ultraviolet detector is preferably sensitive to emitted wavelengths in the range of 315-420 nm, more preferably 340-360 nm, and most preferably, 345 nm.
- the ultraviolet radiation source is preferably operative to irradiate at approximately 320-370 nm, more preferably at approximately 340 nm, and the ultraviolet detector is preferably sensitive to emitted wavelengths in the range of 400-550 nm, more preferably 450-470 nm, and most preferably, 460 nm.
- the ultraviolet radiation source is preferably operative to irradiate at approximately 340-500 nm, more preferably at approximately 370-460 nm, and the ultraviolet detector is preferably sensitive to emitted wavelengths in the range of 500-600 nm, more preferably 520-560 nm, and most preferably, 530 nm.
- the radiation emitted by the target correlates with the glucose level of the patient.
- the spectral information can be converted into a number correlative to standard blood glucose determinations.
- the instrument further comprises a radiation detector positioned to receive radiation emitted from an excited target at the tissue surface.
- the instrument may further include a processing circuit operatively connected to the radiation detector and operative to translate a level of emitted radiation into a measurable signal that is representative of, or may be correlated with, the blood glucose level.
- the instrument comprises analyzing means operatively connected to the radiation detector for analyzing radiation detected by the radiation detector and translating the detected radiation to an indication of the tissue glucose level.
- the analyzing means preferably analyzes one or more parameters selected from the group consisting of wavelength of fluorescence, overall fluorescence, relative peak ratios, spectral shapes, peak shifts, band narrowing, band broadening and intensity. It may comprise means for applying one or more multi variate analysis methodologies selected from the group consisting of PLS, PCR, LDA, MLR, stepwise LR, wavelets and neural networks.
- the radiation source is ultraviolet light. Alternately, visible light may be used.
- the source may be a laser, diode or lamp.
- the radiation source may comprise a flexible- fiber optic arm or probe that directs the radiation to the target.
- the light is directed onto the skin and collected through other optical means (e.g. lens).
- the probe may comprise a glass or quartz fiber and may be flexible and easily manipulated to examine a site anywhere on the patient's skin.
- the portion of skin irradiated may be between about 4 square cm or more but as little as about 0.2 square cm. However, the portion of skin irradiated may be as small as about 0.5 to 1 square cm or less.
- the radiation source may further comprise means for applying the source to the tissue surface at a constant pressure and temperature at the tissue surface.
- the portion is a site which is most easily measurable on the patient such as on the arm or leg. Differences in pigmentation between different areas of the body as well as different patients can be factored or eliminated through selection of control input, and overcome.
- the radiation source is configured to emit excitation radiation at a plurality of different wavelengths and the radiation detector is configured to synchronously scan radiation emitted by the target with the excitation radiation (e.g. an excitation-emission map, in which the excitation-emission pairs for fluorescence are repreented in a three dimensional array with the X and Y axes representing excitation and emission wavelengths respectively with the Z axis corresponding to the fluorescence intensity returned at excitation wavelength X and emission wavelength Y).
- the radiation source may be an ultraviolet light or a visible light source.
- Useful targets include structural matrix, cellular, or mitochondrial components, or other cellular components reflective of metabolic activity.
- the target may be selected from the group consisting of a pepsin-digestible collagen cross link, a collagenase-digestible collagen cross link, a non-pepsin digestible collagen cross link, free tryptophan, tryptophan-containing proteins, elastin cross links, FAD, flavoproteins, NADH, other matrix, cellular or mitochondrial components, or combinations thereof.
- the target is tryptophan and the radiation source is operative to emit radiation at between about 285 and 305 nm, or, more preferably, about 295 nm.
- the radiation detector is operative to detect radiation at between about 315 and 420 nm.
- the target is PDCCL and the radiation source is operative to emit radiation at between about 330 and 345 nm, or, more preferably, 335-340 nm.
- the radiation detector is operative to detect radiation at between about 370 and 410 nm.
- the target is NADH and the radiation source is operative to emit radiation at between 320 and 370nm, or, more preferably, 340nm.
- the radiation detector is operative to detect radiation at between about 420 and 520nm.
- the target is FAD or other flavoproteins and the radiation source is operative to emit radiation at between 320 and 500nm, or, more preferably, 370nm and 460nm.
- the radiation detector is operative to detect radiation at between about 500 and 560nm.
- the instrument may further comprise a display such as, for example, a visual, auditory or sensory display operatively connected to the processing circuit or analyzing means and operative to display the glucose level indication.
- the analyzing means may comprise means for monitoring a trend in glucose levels.
- the instrument further comprises a device responsive to the analyzing means that is operative to administer a medication, such as insulin via an insulin pump, to a patient at a rate that corresponds to the glucose level indication or trend.
- the instrument may include alarm means operationally coupled to the analyzing means that is activated when the glucose level indication exceeds a first predetermined value, falls below a second predetermined value or varies more than a predetermined amount (i.e., 20%) from a third predetermined value.
- alarm means operationally coupled to the analyzing means that is activated when the glucose level indication exceeds a first predetermined value, falls below a second predetermined value or varies more than a predetermined amount (i.e., 20%) from a third predetermined value.
- the instrument may also include a normalizing detector responsive to another target that provides normalizing information to the processing circuit to normalize the glucose level indication.
- the instrument may have normalizing means which provides normalizing information to the analyzing means to normalize the glucose level indication.
- the normalizing means may normalize for age, UV damage, skin color, temperature, hydration and pH.
- the instrument may include means for measuring scattering.
- One such means comprises an illuminating means that emits radiation at an angle greater than 60 degrees to the target or, alternatively, illuminating means which emits radiation at between about 300 to 700 nm.
- the instrument may further include means for measuring absorbance and the analyzing means may comprise means for adjusting the glucose level indication based on the scattering and absorbance measured.
- data may be analyzed and transmitted to a pump or other servo mechanism responsive to the processing circuit.
- the pump is incorporated into the system such that the pump administers insulin or other medication to the patient at a rate that corresponds to the glucose level signal.
- the pump may be internal or external to the body. It may be designed for long term management of diabetes or for acute regulation of glucose infusions for nutritional supplementation.
- an embodiment of the glucose monitor of the invention includes a Xenon arc (Xe-arc) lamp, double excitation and emission monochromators, a photo multiplier device, a simple current amplifier and a flexible probe.
- the probe may comprise fiber optic bundles which allow convenient evaluation of living systems.
- This embodiment can take the form of a multipurpose skin spectrometer or it may be modified to create a unit optimized to provide data specifically relevant to signals correlating with blood glucose.
- One advantage of utilizing fluorescent excitation spectra compared to fluorescence emission spectra is that the former are similar to absorption spectra, which aids in the separation and identification of the individual fluorophores in a complex spectrum.
- a Xe-arc or mercury lamp in combination with an excitation monochromator avoids the major constraint of laser sources, namely the limited number of excitation wavelengths.
- other types of sources such as a diode laser, coupled with enhanced spectral analysis algorithms may be used. These algorithms may also incorporate variables such as skin coloration, type, age, exposure, temperature, skin hydration, pH, perfusion state, etc., all of which may be analyzed during testing. Hardware modifications and calibrations may be incorporated to take into account these and other variables. Specific algorithms and software may be embedded into a dedicated processor.
- one design may comprise a night hypo/hyperglycemia monitoring instrument which is programmed to alarm by trending analysis parameters that correlate with significant changes in blood glucose.
- monitoring could be performed with a transportable fiber-based fluorescence spectrophotometer with double monochromators, both on the excitation and emission paths. This allows the evaluation of different subsets of collagen cross links and tryptophan signals and other fluorophores present (NADH, FAD, flavoprotein) as well as allowing the estimation of epidermal melanin pigmentation or other tissue pigments.
- Optimized instruments e.g. Fluorolog
- Another embodiment uses a fiber-based fluorescence spectrometer with two double monochromators and a high intensity excitation light source (i.e. 350 W
- the double monochromator design minimizes stray light, which tends to be high because of the high level of light scattering by the tissues.
- the probe is a fiber optic device that allows collection of data from different skin sites on the body. Probe design is optimized to permit ease of use and reproducibility. Optimization of light sources, filters and software can be designed to perform multiple scans that maximize the collagen fluorescence signals. In one embodiment, three scans are performed. This provides information on PDCCL (340/390 nm), the collagenase digestible collagen cross links (370/460 nm)and the collagen elastin cross links (420/500 nm), NADH (340/460 nm), FAD (370 and 460/530 nm), among other species.
- the system may also provide data on tryptophan, an epidermal fluorophore having an excitation wavelength of 290-315 nm and an emission wavelength of 340-400 nm, among other species.
- Additional scan types include emissions scans and synchronous scans, and excitation- emission maps.
- Devices may be small and lightweight desktop units useful in health care provider or home settings.
- a remote probe may be connected to the system through a flexible fiber optic bundle.
- Data output may consist of a reporting of a quantitative number that correlates with blood glucose readings, along with spectral data, which may be displayed on a separate small I/O terminal or laptop computer.
- the software further contains diagnostic overlay capabilities.
- multiple excitation and emission wavelengths may be used without departing from the spirit and scope of the invention.
- multiple excitation wavelengths may be used while doing emission scans.
- multiple emission wavelengths can be evaluated while doing excitation scans.
- 260 to 510 nanometers are utilized in a synchronous 50 (sync50) scan.
- Another device allows monitoring of glucose levels by providing spectral information reflective of glucose levels on a continuous or repetitive basis. Analysis may be enhanced by comparing with temporally proximal and distal data points. In one embodiment, this would be used throughout the night with a built-in alarm, to alert the patient to abnormal decreases or increases in glucose levels.
- the unit which may be the size of a clock radio, may have a fiber optic cable to connect to the patient, similar to existing apnea monitors and pulse oxymeters.
- Another portable device may be placed in contact with the skin for periodic momentary glucose readings.
- the device may have an LCD readout for glucose levels or an auditory reporting capacity, or both, as well as memory to store several hundred glucose readings and a data output to download stored data.
- the device may alternately have a sensor unit directly attached to the patient that is coupled to an analyzer or alert system via RF communication, thereby obviating the need for direct physical connection by cable/fiber/wire between the patient and the unit.
- An alarm may be operationally coupled to the processing circuit or analyzing means such that the alarm is activated when the glucose level indication exceeds a first predetermined value (such as 200 mg/dL), falls below a second predetermined value (such as 70 mg/dL), or varies more than 20% or any desired amount from a third predetermined value (such as the previously measured level or a baseline level determined for the patient). Alternately, the alarm may be triggered in response to a more complex algorithmic analysis of data or based on evaluation by trending analysis over time.
- the instrument may further comprise a normalizing detector responsive to another target in the tissue, such that the processing circuit or analyzing means is responsive to the normalizing detector to normalize the glucose level indication.
- a current or latest glucose level signal may be normalized by comparing it to a previously determined glucose level signal which has been calibrated by comparing it directly with a conventionally determined blood glucose level.
- normalization may involve comparison of emissions from the same target but at another wavelength, comparison of emissions from a non-target or another structural or circulating component of the body, or simply taking a reading from another skin site. Normalization may also be performed by comparison to similar data from another point or points in time taken from the same individual, or utilizing a stored database or spectral library. Normalizing may alternately comprise obtaining a baseline signal before any prolonged activity where continual measurements would be difficult such as, for example, before driving or sleeping, and watching for changes or trends of changes.
- the previously determined glucose level signal may also be compared with a level assessed from a simultaneously drawn blood sample.
- scattering evaluation and absorption such as by skin chromophores, may be factored into the normalizing process.
- the instrument may optionally comprise means for measuring scattering re-emitted from the tissue.
- the means for measuring scattering may comprise a skin illuminating means that emits radiation at an angle greater than 60 degrees to the target or it may comprise a skin or tissue illuminating means which emits radiation at between about 280 to 700 nm. Re-emitted radiation is then collected and analyzed. Generally, longer wavelengths penetrate down into dermis. The use of a 60 degree angle of illumination to the skin surface separates the diffuse from the spectral reflectance as there is essentially no spectral reflectance with the fibers placed on the skin.
- the instrument may include a portable housing in which the radiation source, the radiation detector and the processing circuit are disposed.
- the instrument may include a battery compartment disposed in the housing and a pair of battery contacts operatively connected to the ultraviolet radiation source, the ultraviolet radiation detector, and the processor. Data can be electronically recorded, stored or downloaded for later review or analysis.
- the instrument may further comprise attachment means for attaching the radiation source, a portion of, or all of the device to the patient.
- the portable housing, the ultraviolet radiation source, the ultraviolet radiation detector, and the processor may be designed so that they weigh in combination less than 3 kg, more preferably less than 1 kg, and most preferably, less than 0.5 kg.
- the instrument may optionally include an attachment mechanism for attaching the housing to the patient.
- the instrument can be miniaturized; in such an embodiment, a microprocessor is incorporated onto a dermal patch, which may be operatively connected to other devices that provide input directly to a pump or other biodelivery system, such as a trans mucosal or inhalational system, which may deliver insulin, glucose-containing solutions or other appropriate medication to the patient.
- the instrument may also be constructed using small components composed of inexpensive, possibly recyclable materials such as plastics and paper, so that the entire instrument or a significant portion is disposable.
- the entire device can be incorporated into a patch worn anywhere on the body and secured with adhesive tape, hook-and-loop fastener or another suitable means. After expiration or depletion of an integral battery, the patch can be safely and easily disposed of and a new patch secured.
- Such instruments weigh less than 1 kg, preferably less than 0.5 kg and more preferably less than 0.1 kg.
- the processing circuit or analyzing means is preferably operative to translate the level of detected radiation into a measurable glucose level signal that is indicative of the glucose level in the tissue.
- the signal may be directly evaluated, or it may be compared to stored reference profiles, to provide an indication of changes from previous levels or trends in the patient's glucose level.
- a preferred embodiment measures radiation or fluorescence following irradiation of the skin
- the present invention can also be used to assess glucose levels by evaluation of other tissues. For instance, glucose levels may be assessed in accordance with the present invention by detecting radiation or fluorescence following irradiation of the surface of other tissues, such as mucous membranes, or irradiation of the mucosa, submucosa or serosa of any organ.
- One embodiment of the invention is directed to a non-invasive analyte monitoring instrument comprising a radiation source for directing excitation radiation to a portion of a tissue surface, such as skin, a radiation detector, and a processing circuit.
- a radiation source for directing excitation radiation to a portion of a tissue surface, such as skin, a radiation detector, and a processing circuit.
- the analyte being detected is glucose.
- the radiation source is a visible light source or an ultraviolet light source that emits excitation radiation at least one wavelength that excites a target in the tissue.
- the excited target emits radiation that correlates with the analyte level of the tissue.
- the radiation from the excited target received at the surface may be affected by factors such as absorption of emissions and scattering.
- radiation received at the surface may be quenched or amplified by one or more matrix, cellular, or mitochondrial components, or any other cellular component reflective of metabolic activity, in the tissue.
- the radiation detector is positioned to receive radiation emitted from the surface of the tissue.
- the radiation received at the surface of the tissue provides an analyte level indication of the patient.
- the processing circuit is operatively connected to the radiation detector and translates emitted radiation to a measurable signal to obtain the analyte level indication.
- Another aspect of the invention relates to a non-invasive method of detecting a glucose concentration or level in a tissue or body in vivo comprising the steps of: exciting a non-glucose target in the tissue causing the excited target to emit radiation such that the radiation received at a tissue surface is indicative of a glucose level of a patient; detecting radiation emitted by the target and transmitted through the intervening tissue to the surface; and determining the glucose level or trend in glucose levels from the radiation detected.
- the excitation radiation is ultraviolet or visible light.
- the excitation radiation may have a wavelength of about 280-650 nm.
- the radiation emitted by the target is fluorescent radiation.
- the target is a matrix target such as collagen cross links, a cellular component (e.g. an intracellular tryptophan-containing protein), or a mitochondrial component such as mitochondrial NADH.
- the method may optionally include the step of determining whether to take steps to adjust the patient's glucose level in response to the derived or determined glucose level, followed by the step of administering insulin or another pharmaceutical composition in response thereto.
- glucose or insulin administration may be adjusted in order to adjust the patient's glucose level.
- the method may include any one or more of the steps of reporting the information to the patient, determining whether to take steps to adjust the glucose level, recommending a dosage, or administering the composition, such as insulin, to the patient in response to the indication derived.
- the method may comprise the step of adjusting the glucose level of the patient in response to the glucose level or trend determined. This may be accomplished by administering insulin or another medication to the patient, by using a syringe, a pump or another suitable biodelivery system, mechanical or chemical, which may be implanted or external to the body.
- the method may also include the step of displaying a glucose level indication related to the indication derived or providing a warning to the patient.
- the method may further include the step of normalizing the glucose level determined, such as by normalizing for one or more variables selected from the group consisting of temperature, perfusion state, age, UV damage, skin color temperature, hydration and pH.
- the steps of exciting, detecting, and determining may be performed continuously or at any appropriate interval, for example, by the minute, hourly, daily or every other day for the same patient and over a period of days, weeks, months or years.
- the method may include actuating an alarm in response to the glucose level when the glucose level exceeds a predetermined first level, falls below a predetermined second level or varies more than a set percentage, such as for example, 10%, 20%, 30%, 50% or 100% or more from a predetermined third level, or changes in such a way that meets criteria of a specifically designed algorithm.
- the method may further comprise the step of measuring scattering re-emitted from the skin or irradiated tissue surface and utilizing the resulting data to initiate or assist in actuating a process aimed at adjusting the glucose level accordingly.
- the step of determining the glucose level may comprise analyzing the radiation detected using one or more multi variate analysis methodologies selected from the group consisting of PLS, PCR, LDA, MLR and stepwise LR.
- the step of exciting may comprise irradiating a target with excitation radiation at a plurality of wavelengths and the step of detecting radiation may comprise the step of synchronously scanning the emitted radiation and excitation radiation or the acquisition of an excitation-emission map.
- the step of excitation may comprise application of a probe incorporating a radiation source to the skin.
- the probe may be applied to the skin at a constant pressure or temperature.
- the position of the probe on the skin may be varied during detecting.
- Another embodiment of the invention is directed to a method for detecting diabetes in a patient comprising: exciting a non-glucose target using ultraviolet or visible radiation, such that the collection of light from the excited target is indicative of a glucose level of a patient or state of diabetes; detecting radiation emitted by the target; determining the glucose level or state of diabetes from the radiation detected; and detecting diabetes based on the determined glucose level provided by the collection of light from the excited target.
- Instruments and methods of the invention are advantageous in that they provide information relative to blood glucose and permit glucose levels to be evaluated non invasively. Such non-invasive instruments allow people with diabetes to monitor glucose levels without the pain, inconvenience, and risk of infection associated with obtaining a blood sample. By making monitoring safer and more convenient, people with diabetes can monitor their glucose levels more frequently and therefore control levels more closely. Safer and more convenient glucose level monitoring reduces the likelihood of measurements being skipped.
- the transmitter may remotely transmit the signal to a pump, such as a servo pump, having a receiver responsive to the transmitted signal.
- the pump is preferably responsive to information derived from or analysis of the spectral signal.
- the pump may then provide insulin or other appropriate medication to the patient. Alternately, or in addition, the information may be sent to a remote monitor.
- the instruments and methods of the present invention can also be used in forensic applications, to allow the non-invasive and non-destructive assessment of forensic tissues.
- the instruments and methods may be used to detect and diagnose diabetes, monitor the progression of diabetes, and detect and monitor other disorders involving hyper or hypoglycemia or abnormal blood sugar metabolism.
- the term in vivo is used to refer to living material, it is intended herein to encompass forensic applications as well.
- FIG. 2 depicts a glucose level monitoring instrument 10 including source driving circuit 12 having an output provided to an input 13 of a source 14.
- Source driving circuit 12 controls the illumination, provided by source 14.
- Source driving circuit 12 may take a number of forms, depending on the nature of the source and the acquisition. Examples include a regulated power supply or a pulsed modulator.
- Source 14 preferably comprises an ultraviolet light source, such as a continuous mercury lamp, a pulsed or continuous xenon flash lamp, or a suitable laser.
- Useful lasers include, but are not limited to, nitrogen lasers, doubled OPO (tunable laser) and tripled Nd YAG pump devices.
- Useful pulsed sources include a 2-channel lock-in amplifier or a gated CCD. The output of source 14 may be filtered to restrict illumination to within excitation bands of interest. Its intensity (and pulse width if applicable) is preferably set at a level that minimizes exposure while optimizing signal-to-noise considerations.
- the source is positioned to illuminate an area of interest on the patient's skin 16.
- Glucose level monitoring instrument 10 also includes a detector 18 that is sensitive to ultraviolet and visible light emitted by the species that is excited by the source 14.
- the detector has an output 15 operatively connected to an input of an acquisition interface 20, which may be an analog-to-digital converter with an analog input operatively connected to the detector output.
- a digital output port 21 of the acquisition interface is operatively connected to processor 22.
- Processor 22 is operative to convert the digital detector output signal into a glucose level signal.
- the processor may perform this conversion by applying various signal processing operations to the signal, by comparing signal data with stored reference profiles, or by other appropriate methods.
- It has an output 23 provided to a display 24, permitting the glucose level indication to be presented to the user.
- the output may be directly provided to display 24, or sent remotely via a transmitter.
- Display 24 may be an alphanumeric display which displays the glucose concentration as a percentage.
- the glucose level monitor instrument 10 may also include a medication delivery device, such as insulin pump 26, which is responsive to the glucose level signal or other spectroscopic data or analysis provided by processor 22.
- a transmitter may be used to transmit the glucose level signal of processor 22 to the pump.
- the pump is configured so that it converts the glucose level signal received from processor 22 into an insulin dispensing rate.
- a single bolus of insulin may also be administered based on the glucose level signal.
- the medication delivery device can also deliver another therapeutic substance, or administer an electrical, chemical, or mechanical stimulus.
- Miniaturized devices may be constructed of disposable materials such as plastics and paper to further reduce cost. Instrument 10 may be implemented in a number of different ways.
- the various elements described may be implemented at a board level, with the various elements described being separate components, mounted on a circuit board. Many of the elements may also be integrated into a dedicated special-purpose integrated circuit allowing a more compact and inexpensive implementation. Alternatively, the components may be miniaturized further to create an implantable device or a dermal patch. In integrating and miniaturizing the various functions of the instrument, many of them may be combined. Important algorithms may be embedded.
- Instrument 10 may also include a normalizing section.
- the normalizing section is designed to reduce or eliminate the effect of variations, such as the intensity of source 14 or skin heterogeneity or day to day variations in the patient's tissue.
- a normalizing section may include a second detector that is responsive to a species in the skin that fluoresces but does not respond to glucose concentration. It may also normalize to a signal collected at another time, another site, or another wavelength or from a different internal or external target.
- Processor 22 may receive signals from the two detectors and derive a normalized glucose level signal.
- instrument 10 includes a portable housing bearing ultraviolet radiation source 14, ultraviolet radiation detector 18, acquisition interface 20 and processor 22. Instrument 10 maybe powered via battery contacts by a battery contained in the battery compartment located within the housing.
- the entire assembly weighs in combination less than 20 kg, preferably less than 10 kg and more preferably less than 1 kg.
- Highly portable embodiments which weigh under 1 kg may be attached to the patient in a monitoring position, such as by an elastic or hook-and-loop fastener strap.
- the instrument may further include a system response detector similar to correction system, which allows system response to be checked daily.
- a physician or the patient places source 14 close to an area of interest on the patient's skin 16.
- this area is one that is not regularly exposed to sunlight, such as the inside of the upper arm.
- the physician or patient may then start the instrument's monitoring sequence.
- the monitoring sequence begins with driving circuit 12 producing a driving signal that causes source 14 to irradiate the area of interest on the surface of the skin 16 with one or more bands of ultraviolet radiation.
- the spectral content of this radiation is selected to cause one or more targets within the skin to fluoresce.
- targets may include tryptophan, tryptophan-containing proteins, collagen cross links, NADH, flavoproteins, or other suitable targets.
- the excitation/emission wavelengths for tryptophan-containing proteins, collagen cross links, NADH and flavoproteins are 295/340-360 nm, 335-340/380-400 nm, 340/460 nm, and 370 and 460/530 nm, respectively.
- the excitation and emission wavelengths are representative of the molecular species targeted. Under circumstances where the target is responsive to multiple different wavelengths and provides different information from each, or where targets and non-targets are responsive to the same wavelength, more accurate and qualitative values may be obtained by identifying and eliminating background and other interfering data.
- the target absorbs the radiation from the source and emits it back to detector 18. More specifically, fluorescence is emitted from the target molecule and/or light is scattered by the target then remitted.
- Detector 18 derives a signal representative of the received emitted radiation and provides it to the acquisition interface 20.
- Acquisition interface 20 translates the derived signal into a digital value, which it provides to processor 22.
- Processor 22 converts the digital value into a display signal, which it provides to display 24.
- the display signal may take the form of an alphanumeric representation which correlates with the concentration of glucose in the blood, or it may include another kind of display signal to be used with another type of display.
- a color coding scheme to indicate levels of glucose, or indicate dosage amounts to the patient on the display based on the signal received at the detector.
- the display need not be a visual display; tactile actuators, speakers, or other machine-human interfaces may be employed.
- the glucose level signal produced by the processor may be directly displayed to indicate the patient's glucose level.
- the processor may first compare the data from the detector with stored reference profiles, such as the patient's prior levels, to provide information regarding trends in the patient's glucose level.
- Still another aspect of the invention is related to a glucose monitoring system with alarm features. Parents of children with diabetes are under a continuous threat that a severe hyper- or hypoglycemic event may occur without their knowledge, such as during the night, with potentially fatal consequences.
- this aspect of the invention is related to a monitoring device with an alarm that alerts a parent or other interested person in the event of large or dangerous changes or trends in the blood glucose levels of a patient.
- the device reports systemic hyperglycemic and/or hypoglycemic events using fluorescent detection of alterations in the environment of matrix, cellular, or mitochondrial components, or other cellular components reflective of metabolic activity, that reflect changes in blood glucose.
- the device may detect the change in fluorescence from the excitation of another suitable species, such as tryptophan, or changes in quenching.
- the device may be completely portable, miniaturized and/or disposable allowing its use in nearly any environment.
- the alarm may be any suitable alarm including, but not limited to, a sound alarm or a radio transmitter that activates a sound or light emitting unit in the proximity of the parents or other interested person.
- the alarm may be audible, visible, vibrating or any other sensory detectable type.
- the patient's glucose level is measured once or at a plurality of intervals shortly before the patient goes to sleep to determine a baseline glucose level.
- the device is programmed to take measurements of the patient's glucose level at periodic intervals during the night, and to then compare these results with the baseline. If the glucose level varies more than a predetermined percentage from the baseline either simply or utilizing specifically designed algorithms, an alarm sounds.
- the alarm is activated when the glucose level varies more than 5%, 10%, 20% or more from the previously determined baseline or in accordance with a previously defined set of parameters or specifically designed algorithms. Alternately, or in addition, the alarm is triggered if the patient's blood glucose level exceeds a first predetermined level (i.e., it exceeds 200 mg/dL) or if it falls below a second predetermined level (i.e., it falls below 70 mg/dL). When the alarm sounds, the patient can then be administered insulin (or other suitable medication) if the glucose level is too high, or can be given a source of sugar if the glucose level is too low.
- a first predetermined level i.e., it exceeds 200 mg/dL
- a second predetermined level i.e., it falls below 70 mg/dL
- the alarm may be triggered if other analysis or trending patterns occur or if the rate of change exceeds a predetermined amount.
- the processor of this device may include means for storing and displaying a plurality of sequential measurements, so that trends which occur during the night or during other time periods of interest may be saved and evaluated.
- the measurements can be taken continuously or repetitively at predetermined intervals.
- a patient can be periodically monitored after the administration of one or more of the various forms or sources of insulin (i.e., lente, ultralente, semilente, regular, humalog, NPH etc.) or other glucose regulatory therapies to determine or help to determine the most suitable treatment protocol for the patient. This may be influenced by a comparison to other readings over time, a broader data base, a derivation based on the slope of the change of the signal over time and where on the scale of patient risk a particular assigned glucose might fall.
- insulin i.e., lente, ultralente, semilente, regular, humalog, NPH etc
- the fluorescence signals measured from the excitation of PDCCL and other tissue components are affected by the changes in the scattering properties of the superficial structural matrix. As the electrolyte balance in the micro environment of collagen cross links changes, changes are induced in fluorescence. Changes in fluorescence also can occur with modification of metabolic components or from alterations in the equilibria of fluorescent metabolic compounds.
- the change in electrolytes also produces a change in the local index of refraction and thus a change in the scattering properties.
- the change in scattering causes a change in the fluorescence. Specifically, scattering will change the detectable or measurable fluorescence by altering the intensity of the exciting light or diminishing the emitted fluorescence. It may also alter the effective sampling volume, but it does not directly affect the fluorescence.
- the matrix scatters light independent of the local refractive index. These are two separate events. Correction can be made for changes in the measured fluorescence induced by scattering.
- FIG. 10A A diagram depicting fluorescence of two species sensitive to glucose concentration following i ⁇ adiation of the skin is depicted in Figure 10A.
- Incoming radiation at wavelength ⁇ i is directed towards the skin. It penetrates the stratum corneum. If ⁇ i is 295 nm, fluorescent radiation ( ⁇ o) will be emitted at 345 nm by tryptophan in the epidermis of the skin. If ⁇ i is 335 nm, fluorescent radiation will be emitted ( ⁇ o) at 390 nm by the collagen cross links in the dermis.
- FIG. 10B A diagram depicting a scattering according to a scattering model is depicted in Figure 10B which shows collagen cross links in the dermis bending incoming light ( ⁇ i) in different directions. There emitted light ( ⁇ o) is at the same wavelength as the incoming light ( ⁇ i), but is scattered due to changes in the local index of refraction.
- results from the assessment of scattering can be used to correct for changes in fluorescence induced by changes in the scattering properties of the relevant layers of the dermal matrix.
- another aspect of the invention is related to a device that measures the scattering properties of a target such as superficial collagen dermal matrix in the skin, which is affected by changes in the chemical environment which can be correlated with blood glucose levels.
- a target such as superficial collagen dermal matrix in the skin
- the scattering properties of the skin change with glucose concentration and that these changes are measurable with photon migration techniques in the near infrared (NIR)
- NIR wavelengths provides a sample of the whole dermis and subcutis (does not measure one signal specific for glucose, but rather many signals that are neither specific for glucose nor reliably linked to glucose levels in a linear fashion).
- the present invention assesses the scattering properties of the dermis, as opposed to the deeper layers. Such scattering of polarized light by the dermal matrix is most noticeable in the range 380-700 nm.
- Assessment of scattering in tissue, such as the dermis, associated with changes in blood glucose can most preferably be measured by using short wavelengths (330-420 nm) or launching the illuminating light at large angles (preferably >60°). Short wavelengths are preferably used because they penetrate to a small depth into the dermis. Alternately, changes in scattering induced by the presence of glucose may be measured using light in the visible range of 620-700 nm and looking for changes in signal intensity.
- Increases in fluorescence may be compensated for by decreases in the effective scattering, making the fluorescence signal difficult to separate from background noise.
- fluorescence detection may be enhanced, allowing it to stand on its own merit as a method of indirect measurement of glucose concentration.
- Figure 11 depicts an embodiment in which both fluorescence of the superficial dermis and scattering are evaluated in order to assess glucose levels.
- Instrument 100 comprises a power supply 101 connected via connection 102 to a light source 104.
- Light source 104 may be a lamp, an arc lamp, a laser, or other suitable illumination device.
- Power supply 101 receives feedback 103 from data acquisition controller 122 to regulate the intensity, synchronization or pulse rate of the light emitted from light source 104.
- Light source monitor output 105 which may comprise a PIN diode, Avalanche diode, photo multiplier, CCD or other suitable device, couples the light source 104 to data acquisition controller 122.
- Light 106 is directed to wavelength selection device 107, where an appropriate wavelength is selected, and selected light wavelength output 109 is directed via a fiber, prism or a combination, or directly through the air, to illuminate skin 110.
- Wavelength selection device 107 may comprise a monochromator, a filter or a combination of both. If a laser source is used as light source 104, a filter or other wavelength selection device may not be needed.
- Wavelength selection device 107 is coupled via signal connection 108 to data acquisition controller 122 to enable selection of the wavelength and to verify the present wavelength.
- Fluorescent signals are emitted and scattered light is re-emitted from skin 110.
- the fluorescent light and reflective intensity 111 is picked up by wavelength selective device 112, which may comprise a monochromator, filter or a combination.
- Wavelength selective device 112 provides a light output 114 to detector 115.
- Detector 115 may comprise a photo multiplier, diode, Avalanche diode, CCD or other suitable detection device.
- the signal from detector 115 is transmitted to signal conditioner/processor 120 via signal connector 116.
- Detector 115 is supplied power via power cable connection 117 from power supply 118.
- Data acquisition controller 122 provides input to power supply 118 via signal connection 119 to allow selection of sensitivity or synchronization with the light source.
- Wavelength selection device 112 is coupled via connection 113 to data acquisition controller 122 to select wavelength and verify current wavelength.
- Signal processor/conditioner 120 provides output via output connection 121 to data acquisition controller 122.
- Data acquisition controller 122 is connected via connection 123 to display 125.
- Data acquisition controller 122 may also provide output via connection 124 to an insulin or medication delivery device.
- the above described instrument may also be used as non-invasive device for assessing changes in structural matrix, cells or mitochondria, or the environment of said components, or other cellular components reflective of metabolic activity, due to a variety of conditions including, for example, disease conditions (e.g. infections, cancer), the presence of topical chemicals such as steriods, age, photodamage, and combinations thereof which may provide the general state of health of the patient.
- This embodiment allows the assessment of changes in the structural matrix non-invasively by measuring the combination of fluorescence and scattering, and comparing these results to measurements of developed standards, temporal correlates or surrounding normal tissue.
- This device may be used to assess changes in the collagen matrix brought about by diseases such as diabetes, scleroderma, scarring, or atrophy induced by the use of steroids. It is also useful to assess changes in the matrix due to aging or photoaging and changes induced by long exposures to zero gravity environment. Treatment related changes and drug concentration monitoring are additional clinical and research applications.
- This embodiment may be miniaturized, and may be used clinically and in research applications to evaluate wound healing, protein metabolism, diabetes, collagen diseases and other conditions.
- Useful methodologies include normalizations of spectra and multi variate analyses of all sorts.
- Multi variate analyses include PLS, PCR, LDA, MLR, stepwise LR, etc.
- the collagen cross-links in the superficial or papillary dermis provide large fluorescence signals that are indicative of the state of the collagen matrix. These signals may be monitored non-invasively without interference with the functions of the skin. Specifically, as the matrix is irradiated with UVA, UVB or UVC radiation, the fluorescence of PDCCL decreases. This fluorescent effect recovers following a single exposure; however, the changes induced become permanent after multiple exposures. Degradation of PDCCLs is wavelength dependent. The most effective wavelength range is UVA with a maximum decrease from 335 nm irradiation. 365 nm i ⁇ adiation is much less effective than 335 nm. The fluorescence signals from skin fluorescence with excitation in the
- UVA (320-400 nm) may be used to evaluate the state of the collagen matrix.
- matrix metalloproteinases such as collagenase
- the fluorescence emission degrade from the collagenase digestible collagen cross links.
- degenerative changes in the structural matrix or of matrix, cellular, or mitochondrial components, or other cellular components reflective of metabolic activity maybe assessed, such as changes induced by disease or environmental factors such as diabetes, age, photodamage, topical steroid application, or prolonged exposure to zero-gravity.
- the intensity of scattered light by the dermis changes with aging and with changes in the collagen cross links. If the collagen cross links in the superficial or papillary dermis change, then the amount of light that is scattered by the dermis and its dependence on wavelength will also change. These changes may be monitored by reflectance.
- Another aspect of the invention is related to a device that can measure either fluorescence excited at about 335 nm, fluorescence excited at about 370 nm, fluorescence excited at 460 nm, or a combination of all three, as well as the reflectance spectrum (280-1,100 nm), to thereby provide information on the state (or changes induced) of the structural matrix or environment of tissue matrix, cellular, or mitochondrial components, or other cellular components reflective of metabolic activity.
- a novel device is provided that provides enhanced information on the state of the structural matrix or environment of tissue matrix components.
- Other wavelengths can also be used for excitation, such as a wavelength suitable for exciting tryptophan.
- a preferred embodiment incorporates a light source (Hg) and filters to select either 333 nm, 365 nm or visible broad band.
- the visible excitation may be provided by a tungsten halogen lamp of 1-2 watts or other source.
- the light is then conducted to the skin's surface by fibers, reflective optics or directly, and the fluorescence from the UVA excitations and the reflectance from the visible source are assessed with a photodiode a ⁇ ay type of detectors.
- the fluorescence intensities can then be compared to standard signals from collagen samples (prepared from gelatin).
- the reflectance signal is analyzed for scattering and absorption by iterative methods at wavelengths of 280-820 nm.
- Another aspect of the invention is related to an instrument for assessing changes in a structural, or the environment of, matrix, cellular, or mitochondrial components, or any other cellular component reflective of metabolic activity, of a patient comprising means for measuring fluorescence emitted from the skin, and means for measuring scattering.
- the instrument may further comprise means for measuring absorbance.
- This embodiment may further include means for i ⁇ adiating the tissue with a plurality of wavelengths of excitation light and means for synchronously scanning the fluorescence emitted from the skin with the excitation light.
- the means for measuring fluorescence may comprise measuring one or more parameters selected from the group consisting of wavelength of fluorescence, overall fluorescence, relative peak ratios, spectral shapes, peak shifts, band na ⁇ owing and band broadening.
- Another embodiment is directed to an instrument for assessing changes in the environment or the redox/metabolic state of the matrix, cellular, or mitochondrial components, or other cellular components reflective of metabolic activity, of a tissue comprising: means for measuring fluorescence; means for measuring scattering; and means for measuring absorbance.
- the instrument may further comprise means for determining changes in cellular and or mitochondrial fluorophores.
- Another embodiment is directed to a non-invasive method of assessing a change in the structural matrix, cellular, or mitochondrial components, or any other cellular component reflective of metabolic activity, of a tissue comprising: exposing the tissue to radiation at a first wavelength; detecting fluorescence emitted by exposed tissue; exposing the tissue to radiation of a second wavelength; detecting a scattering re-emitted from the exposed tissue; and deriving an indication representative of the change in the structural matrix of the tissue based on the fluorescence detected and the scattering detected.
- the method may further comprise the step of detecting absorbance.
- the step of detecting fluorescence may comprise detecting one or more parameters selected from the group consisting of wavelength of fluorescence, intensity of fluorescence, overall fluorescence, relative peak ratios, spectral shapes, peak shifts, band na ⁇ owing and band broadening.
- the first wavelength is ultraviolet radiation or is between about 320 and 420 nm
- the second wavelength may be between about 330 and 420 nm.
- the first wavelength and the second wavelength may be the same.
- absorbance in the broad region using ultraviolet and visible radiation of 280-700 nm, or a smaller subset thereof, can be used.
- Important regions of this spectrum include, but are not limited to NADH (340 nm),
- Flavoproteins (370-500 nm), hemoglobin bands (oxy and deoxy) between 400 and 600 nm, and water bands in the NIR region.
- Another embodiment is directed to a non-invasive method of assessing a change in the environment of the matrix, cellular, or mitochondrial components, or other cellular components reflective of metabolic activity, of a tissue comprising: exposing the tissue to radiation at a first wavelength; detecting fluorescence emitted by exposed tissue; exposing the tissue to radiation of a second wavelength; detecting scattering re-emitted from the exposed tissue; detecting absorbance; and deriving an indication representative of the change in the environment of the components of the tissue based on the fluorescence detected, the scattering detected and the absorbance detected.
- Another embodiment is directed to a non-invasive method for monitoring skin or tissue constituents in which information about or signature of a specific blood analyte level or disease process is provided comprising the steps of exciting a target fluorophore; detecting radiation emitted by the fluorophore and transmitted through intervening tissue to the surface; and determining the information or signature from the radiation detected.
- glucose other parameters such as hematocrit, scarring, and healing may be monitored as desired using devices according to the invention.
- constant pressure may be used and the position of the fiber may be moved or varied after every scan to account for skin heterogeneity.
- synchronous scans and temperature monitoring may be incorporated as desired.
- Reflectance spectra from subjects may be used as a means of determining data collection times. For example, by lengthening integration times spectra collected from darkly pigmented skin may be enhanced. Reflectance spectra may be used prior to fluorescence collection to determine the appropriate level of integration for that person's site.
- the plots indicate a significantly lower excitation intensity at 295 nm and a significantly higher excitation intensity at 340 nm for the diabetic mice.
- Urine collected from the animals confirmed that the glucose levels of the diabetic mice were higher at 340 nm for the diabetic mice.
- Figures 7, 8 and 9 depict fluorescence excitation spectra for three human subjects, two males and one female, respectively, before (dashes), 30 minutes after (dotted/dashed line), and 60 minutes after (solid line) the ingestion of 100 grams of glucose.
- the emission monochromator was set to a wavelength of 380 nm.
- Collagen and tryptophan spectra were found to change in ways similar to those for the animal models, although there appear to be individual differences.
- Dashed lines represent measurements before glucose intake.
- Dashed and dotted lines represent changes induced after glucose intake.
- Solid lines represent maximal changes induced by the intake of glucose.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Physics & Mathematics (AREA)
- Medical Informatics (AREA)
- Surgery (AREA)
- Biophysics (AREA)
- Pathology (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Heart & Thoracic Surgery (AREA)
- Veterinary Medicine (AREA)
- Molecular Biology (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Optics & Photonics (AREA)
- Emergency Medicine (AREA)
- Spectroscopy & Molecular Physics (AREA)
- Measurement Of The Respiration, Hearing Ability, Form, And Blood Characteristics Of Living Organisms (AREA)
- Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)
Abstract
Description
Claims
Priority Applications (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CA002400309A CA2400309A1 (en) | 2000-02-18 | 2001-02-20 | Non-invasive tissue glucose level monitoring |
JP2001559349A JP2003522579A (en) | 2000-02-18 | 2001-02-20 | Non-invasive tissue glucose concentration monitoring |
AU2001238517A AU2001238517A1 (en) | 2000-02-18 | 2001-02-20 | Non-invasive tissue glucose level monitoring |
EP01910962A EP1257196A1 (en) | 1999-04-06 | 2001-02-20 | Non-invasive tissue glucose level monitoring |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US09/287,486 US6505059B1 (en) | 1998-04-06 | 1999-04-06 | Non-invasive tissue glucose level monitoring |
US60/183,358 | 2000-02-18 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2001060248A1 true WO2001060248A1 (en) | 2001-08-23 |
Family
ID=23103118
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US2001/005323 WO2001060248A1 (en) | 1999-04-06 | 2001-02-20 | Non-invasive tissue glucose level monitoring |
Country Status (2)
Country | Link |
---|---|
US (1) | US6505059B1 (en) |
WO (1) | WO2001060248A1 (en) |
Cited By (26)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2003039362A1 (en) * | 2001-11-08 | 2003-05-15 | Optiscan Biomedical Corporation | Reagent-less whole-blood glucose meter |
US6958809B2 (en) | 2001-11-08 | 2005-10-25 | Optiscan Biomedical Corporation | Reagent-less whole-blood glucose meter |
US6989891B2 (en) | 2001-11-08 | 2006-01-24 | Optiscan Biomedical Corporation | Device and method for in vitro determination of analyte concentrations within body fluids |
US7061593B2 (en) | 2001-11-08 | 2006-06-13 | Optiscan Biomedical Corp. | Device and method for in vitro determination of analyte concentrations within body fluids |
CN1297232C (en) * | 2004-05-21 | 2007-01-31 | 天津大学 | Optical-circuit-variable airspace light-dividing differencial wavelength spectometer for detecting tissue content and detection method thereof |
CN1299646C (en) * | 2004-05-21 | 2007-02-14 | 天津大学 | Optical-circuit-variable time-domain light-dividing differential wave length spectrometer for detecting tissue content and detection method thereof |
JP2007521072A (en) * | 2003-06-19 | 2007-08-02 | センサー テクノロジーズ リミティド ライアビリティー カンパニー | System, device and method for detecting a specimen by operating a sensor |
EP2182848A1 (en) * | 2007-08-31 | 2010-05-12 | Abbott Diabetes Care, Inc. | Analyte monitoring device and methods of use |
WO2013072275A1 (en) * | 2011-11-14 | 2013-05-23 | Roche Diagnostics Gmbh | Analytical apparatus for detecting at least one analyte in a sample |
CN103196874A (en) * | 2012-01-09 | 2013-07-10 | 纳米及先进材料研发院有限公司 | Aggregation-induced emission (AIE) illuminant Cbased urine protein detection device for monitoring health of people |
US8838195B2 (en) | 2007-02-06 | 2014-09-16 | Medtronic Minimed, Inc. | Optical systems and methods for ratiometric measurement of blood glucose concentration |
US8880137B2 (en) | 1998-04-30 | 2014-11-04 | Abbott Diabetes Care Inc. | Analyte monitoring device and methods of use |
US8915850B2 (en) | 2005-11-01 | 2014-12-23 | Abbott Diabetes Care Inc. | Analyte monitoring device and methods of use |
US8920319B2 (en) | 2005-11-01 | 2014-12-30 | Abbott Diabetes Care Inc. | Analyte monitoring device and methods of use |
US8974386B2 (en) | 1998-04-30 | 2015-03-10 | Abbott Diabetes Care Inc. | Analyte monitoring device and methods of use |
US8979790B2 (en) | 2007-11-21 | 2015-03-17 | Medtronic Minimed, Inc. | Use of an equilibrium sensor to monitor glucose concentration |
US9066695B2 (en) | 1998-04-30 | 2015-06-30 | Abbott Diabetes Care Inc. | Analyte monitoring device and methods of use |
US9078607B2 (en) | 2005-11-01 | 2015-07-14 | Abbott Diabetes Care Inc. | Analyte monitoring device and methods of use |
US9155473B2 (en) | 2012-03-21 | 2015-10-13 | Korea Electrotechnology Research Institute | Reflection detection type measurement apparatus for skin autofluorescence |
US9913604B2 (en) | 2005-02-14 | 2018-03-13 | Optiscan Biomedical Corporation | Analyte detection systems and methods using multiple measurements |
US10478108B2 (en) | 1998-04-30 | 2019-11-19 | Abbott Diabetes Care Inc. | Analyte monitoring device and methods of use |
CN113310957A (en) * | 2021-05-19 | 2021-08-27 | 江南大学 | Method for detecting flavoprotein by using three-dimensional fluorescence spectrum |
US11230727B2 (en) | 2016-10-05 | 2022-01-25 | Roche Diabetes Care, Inc. | Detection reagents and electrode arrangements for multi-analyte diagnostic test elements, as well as methods of using the same |
US11369319B2 (en) | 2016-03-29 | 2022-06-28 | Roche Diabetes Care, Inc. | Method of operating a receiver for receiving analyte data, receiver and computer program product |
US11583227B2 (en) | 2018-11-11 | 2023-02-21 | Biobeat Technologies Ltd. | Wearable apparatus and method for monitoring medical properties |
US12024735B2 (en) | 2021-12-10 | 2024-07-02 | Roche Diabetes Care, Inc. | Detection reagents and electrode arrangements for multi-analyte diagnostic test elements, as well as methods of using the same |
Families Citing this family (423)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
MX9702434A (en) | 1991-03-07 | 1998-05-31 | Masimo Corp | Signal processing apparatus. |
US5490505A (en) * | 1991-03-07 | 1996-02-13 | Masimo Corporation | Signal processing apparatus |
US5638818A (en) * | 1991-03-21 | 1997-06-17 | Masimo Corporation | Low noise optical probe |
US8019400B2 (en) * | 1994-10-07 | 2011-09-13 | Masimo Corporation | Signal processing apparatus |
EP1905352B1 (en) | 1994-10-07 | 2014-07-16 | Masimo Corporation | Signal processing method |
US6229856B1 (en) | 1997-04-14 | 2001-05-08 | Masimo Corporation | Method and apparatus for demodulating signals in a pulse oximetry system |
US6002952A (en) | 1997-04-14 | 1999-12-14 | Masimo Corporation | Signal processing apparatus and method |
US6728560B2 (en) | 1998-04-06 | 2004-04-27 | The General Hospital Corporation | Non-invasive tissue glucose level monitoring |
US6721582B2 (en) * | 1999-04-06 | 2004-04-13 | Argose, Inc. | Non-invasive tissue glucose level monitoring |
US7899518B2 (en) | 1998-04-06 | 2011-03-01 | Masimo Laboratories, Inc. | Non-invasive tissue glucose level monitoring |
US20020091324A1 (en) * | 1998-04-06 | 2002-07-11 | Nikiforos Kollias | Non-invasive tissue glucose level monitoring |
US6949816B2 (en) | 2003-04-21 | 2005-09-27 | Motorola, Inc. | Semiconductor component having first surface area for electrically coupling to a semiconductor chip and second surface area for electrically coupling to a substrate, and method of manufacturing same |
ATE521277T1 (en) | 1998-06-03 | 2011-09-15 | Masimo Corp | STEREO PULSE OXIMETER |
EP1108207B1 (en) * | 1998-08-26 | 2008-05-07 | Sensors for Medicine and Science, Inc. | Optical-based sensing devices |
US6721585B1 (en) | 1998-10-15 | 2004-04-13 | Sensidyne, Inc. | Universal modular pulse oximeter probe for use with reusable and disposable patient attachment devices |
USRE41912E1 (en) | 1998-10-15 | 2010-11-02 | Masimo Corporation | Reusable pulse oximeter probe and disposable bandage apparatus |
US7245953B1 (en) | 1999-04-12 | 2007-07-17 | Masimo Corporation | Reusable pulse oximeter probe and disposable bandage apparatii |
US6721583B1 (en) * | 1998-11-19 | 2004-04-13 | The United States Of America | Method for non-invasive identification of individuals at risk for diabetes |
CA2356623C (en) * | 1998-12-23 | 2005-10-18 | Medispectra, Inc. | Systems and methods for optical examination of samples |
US6463311B1 (en) | 1998-12-30 | 2002-10-08 | Masimo Corporation | Plethysmograph pulse recognition processor |
US6684090B2 (en) | 1999-01-07 | 2004-01-27 | Masimo Corporation | Pulse oximetry data confidence indicator |
US6770028B1 (en) * | 1999-01-25 | 2004-08-03 | Masimo Corporation | Dual-mode pulse oximeter |
US20020140675A1 (en) * | 1999-01-25 | 2002-10-03 | Ali Ammar Al | System and method for altering a display mode based on a gravity-responsive sensor |
US6360114B1 (en) * | 1999-03-25 | 2002-03-19 | Masimo Corporation | Pulse oximeter probe-off detector |
US6515273B2 (en) * | 1999-08-26 | 2003-02-04 | Masimo Corporation | System for indicating the expiration of the useful operating life of a pulse oximetry sensor |
ATE429171T1 (en) * | 1999-09-30 | 2009-05-15 | Diagnoptics Holding B V | METHOD AND DEVICE FOR DETERMINING THE AUTOFLUORESCENCE OF SKIN TISSUE |
US6377829B1 (en) | 1999-12-09 | 2002-04-23 | Masimo Corporation | Resposable pulse oximetry sensor |
US6950687B2 (en) | 1999-12-09 | 2005-09-27 | Masimo Corporation | Isolation and communication element for a resposable pulse oximetry sensor |
WO2001060247A1 (en) | 2000-02-18 | 2001-08-23 | Argose, Inc. | Generation of spatially-averaged excitation-emission map in heterogeneous tissue |
US6430525B1 (en) * | 2000-06-05 | 2002-08-06 | Masimo Corporation | Variable mode averager |
US7553280B2 (en) * | 2000-06-29 | 2009-06-30 | Sensors For Medicine And Science, Inc. | Implanted sensor processing system and method |
ATE434970T1 (en) * | 2000-08-18 | 2009-07-15 | Masimo Corp | TWO-MODE PULSE OXIMETER |
US6766187B1 (en) * | 2000-09-18 | 2004-07-20 | Lumenis Inc. | Method for detecting coagulation in laser treatment of blood vessels |
US6560471B1 (en) | 2001-01-02 | 2003-05-06 | Therasense, Inc. | Analyte monitoring device and methods of use |
US7041468B2 (en) | 2001-04-02 | 2006-05-09 | Therasense, Inc. | Blood glucose tracking apparatus and methods |
US7139598B2 (en) * | 2002-04-04 | 2006-11-21 | Veralight, Inc. | Determination of a measure of a glycation end-product or disease state using tissue fluorescence |
US20070276199A1 (en) * | 2002-04-04 | 2007-11-29 | Ediger Marwood N | Determination of a Measure of a Glycation End-Product or Disease State Using Tissue Fluorescence |
JP4498636B2 (en) | 2001-04-27 | 2010-07-07 | 日本サーモスタット株式会社 | Thermostat device |
EP1386140A1 (en) * | 2001-05-04 | 2004-02-04 | Sensors for Medicine and Science, Inc. | Electro-optical sensing device with reference channel |
US6549796B2 (en) * | 2001-05-25 | 2003-04-15 | Lifescan, Inc. | Monitoring analyte concentration using minimally invasive devices |
US6850787B2 (en) * | 2001-06-29 | 2005-02-01 | Masimo Laboratories, Inc. | Signal component processor |
US6697658B2 (en) | 2001-07-02 | 2004-02-24 | Masimo Corporation | Low power pulse oximeter |
AU2002367906A1 (en) * | 2001-10-02 | 2003-12-12 | Alfred E. Mann Institute For Biomedical Engineering At The University Of Southern California | Internal biochemical sensing device |
US20050267326A1 (en) * | 2001-10-02 | 2005-12-01 | Alfred E. Mann Institute For Biomedical Eng. At The University Of Southern California | Percutaneous chemical sensor based on fluorescence resonant energy transfer (FRET) |
US7738032B2 (en) | 2001-11-08 | 2010-06-15 | Johnson & Johnson Consumer Companies, Inc. | Apparatus for and method of taking and viewing images of the skin |
US7106826B2 (en) * | 2002-01-07 | 2006-09-12 | Cdex, Inc. | System and method for adapting a software control in an operating environment |
US7355512B1 (en) | 2002-01-24 | 2008-04-08 | Masimo Corporation | Parallel alarm processor |
US20080172026A1 (en) | 2006-10-17 | 2008-07-17 | Blomquist Michael L | Insulin pump having a suspension bolus |
US6850788B2 (en) * | 2002-03-25 | 2005-02-01 | Masimo Corporation | Physiological measurement communications adapter |
US8140147B2 (en) * | 2002-04-04 | 2012-03-20 | Veralight, Inc. | Determination of a measure of a glycation end-product or disease state using a flexible probe to determine tissue fluorescence of various sites |
US8131332B2 (en) * | 2002-04-04 | 2012-03-06 | Veralight, Inc. | Determination of a measure of a glycation end-product or disease state using tissue fluorescence of various sites |
US7725144B2 (en) * | 2002-04-04 | 2010-05-25 | Veralight, Inc. | Determination of disease state using raman spectroscopy of tissue |
US20070010726A1 (en) * | 2002-10-02 | 2007-01-11 | Alfred E. Mann Inst. For Biomedical Engineering At The University Of Southern California | Internal biochemical sensing device |
AU2003287735A1 (en) | 2002-11-12 | 2004-06-03 | Argose, Inc. | Non-invasive measurement of analytes |
US20040106163A1 (en) * | 2002-11-12 | 2004-06-03 | Workman Jerome James | Non-invasive measurement of analytes |
US7154102B2 (en) * | 2002-11-21 | 2006-12-26 | Cdex, Inc. | System and methods for detection and identification of chemical substances |
WO2004048947A1 (en) * | 2002-11-21 | 2004-06-10 | Cdex, Inc. | Methods and appartus for molecular species detection, inspection and classification using ultraviolet fluorescence |
US6970792B1 (en) * | 2002-12-04 | 2005-11-29 | Masimo Laboratories, Inc. | Systems and methods for determining blood oxygen saturation values using complex number encoding |
US7919713B2 (en) * | 2007-04-16 | 2011-04-05 | Masimo Corporation | Low noise oximetry cable including conductive cords |
WO2004061420A2 (en) | 2002-12-31 | 2004-07-22 | Therasense, Inc. | Continuous glucose monitoring system and methods of use |
US6920345B2 (en) | 2003-01-24 | 2005-07-19 | Masimo Corporation | Optical sensor including disposable and reusable elements |
US6968221B2 (en) * | 2003-03-14 | 2005-11-22 | Futrex, Inc. | Low-cost method and apparatus for non-invasively measuring blood glucose levels |
SG182002A1 (en) * | 2003-04-15 | 2012-07-30 | Sensors For Med & Science Inc | System and method for attenuating the effect of ambient light on an optical sensor |
ES2737835T3 (en) | 2003-04-23 | 2020-01-16 | Valeritas Inc | Hydraulically driven pump for long-term medication administration |
US7039448B2 (en) * | 2003-05-02 | 2006-05-02 | Diramed, Llc | Zero corrected optical blood analyte detector |
US7181219B2 (en) | 2003-05-22 | 2007-02-20 | Lucent Technologies Inc. | Wireless handover using anchor termination |
US8066639B2 (en) | 2003-06-10 | 2011-11-29 | Abbott Diabetes Care Inc. | Glucose measuring device for use in personal area network |
US7003338B2 (en) | 2003-07-08 | 2006-02-21 | Masimo Corporation | Method and apparatus for reducing coupling between signals |
US7500950B2 (en) | 2003-07-25 | 2009-03-10 | Masimo Corporation | Multipurpose sensor port |
US7254431B2 (en) | 2003-08-28 | 2007-08-07 | Masimo Corporation | Physiological parameter tracking system |
US20050090723A1 (en) * | 2003-10-23 | 2005-04-28 | Nassar Saeed | Method and apparatus for non-invasive measuring of physiological glucose concentration in bodies of humans or animals |
US7483729B2 (en) | 2003-11-05 | 2009-01-27 | Masimo Corporation | Pulse oximeter access apparatus and method |
EP1718198A4 (en) | 2004-02-17 | 2008-06-04 | Therasense Inc | Method and system for providing data communication in continuous glucose monitoring and management system |
US7438683B2 (en) * | 2004-03-04 | 2008-10-21 | Masimo Corporation | Application identification sensor |
EP1722676B1 (en) | 2004-03-08 | 2012-12-19 | Masimo Corporation | Physiological parameter system |
CA2464029A1 (en) * | 2004-04-08 | 2005-10-08 | Valery Telfort | Non-invasive ventilation monitor |
WO2006014425A1 (en) * | 2004-07-02 | 2006-02-09 | Biovalve Technologies, Inc. | Methods and devices for delivering glp-1 and uses thereof |
US9341565B2 (en) * | 2004-07-07 | 2016-05-17 | Masimo Corporation | Multiple-wavelength physiological monitor |
US7343186B2 (en) * | 2004-07-07 | 2008-03-11 | Masimo Laboratories, Inc. | Multi-wavelength physiological monitor |
US7937128B2 (en) | 2004-07-09 | 2011-05-03 | Masimo Corporation | Cyanotic infant sensor |
US8036727B2 (en) | 2004-08-11 | 2011-10-11 | Glt Acquisition Corp. | Methods for noninvasively measuring analyte levels in a subject |
US7254429B2 (en) | 2004-08-11 | 2007-08-07 | Glucolight Corporation | Method and apparatus for monitoring glucose levels in a biological tissue |
US8026942B2 (en) * | 2004-10-29 | 2011-09-27 | Johnson & Johnson Consumer Companies, Inc. | Skin imaging system with probe |
US20060189871A1 (en) * | 2005-02-18 | 2006-08-24 | Ammar Al-Ali | Portable patient monitor |
US7647083B2 (en) * | 2005-03-01 | 2010-01-12 | Masimo Laboratories, Inc. | Multiple wavelength sensor equalization |
DE102005013043A1 (en) * | 2005-03-18 | 2006-09-28 | Siemens Ag | Mobile fluorescence scanner for molecular signatures has pulse-operated light source to which energy source is connected |
JP2008537903A (en) | 2005-04-13 | 2008-10-02 | グルコライト・コーポレーシヨン | Data processing and calibration method for blood glucose monitor based on OCT |
US7308292B2 (en) | 2005-04-15 | 2007-12-11 | Sensors For Medicine And Science, Inc. | Optical-based sensing devices |
US20080254661A1 (en) * | 2005-04-29 | 2008-10-16 | Byrne Norman R | Center Connect Single-Sided Junction Block |
US8112240B2 (en) * | 2005-04-29 | 2012-02-07 | Abbott Diabetes Care Inc. | Method and apparatus for providing leak detection in data monitoring and management systems |
US8251904B2 (en) | 2005-06-09 | 2012-08-28 | Roche Diagnostics Operations, Inc. | Device and method for insulin dosing |
US20070004972A1 (en) * | 2005-06-29 | 2007-01-04 | Johnson & Johnson Consumer Companies, Inc. | Handheld device for determining skin age, proliferation status and photodamage level |
US12014328B2 (en) | 2005-07-13 | 2024-06-18 | Vccb Holdings, Inc. | Medicine bottle cap with electronic embedded curved display |
TWI417543B (en) * | 2005-08-05 | 2013-12-01 | Bayer Healthcare Llc | Meters and method of using meters having a multi-level user interface with predefined levels of user features |
US7962188B2 (en) | 2005-10-14 | 2011-06-14 | Masimo Corporation | Robust alarm system |
US7530942B1 (en) | 2005-10-18 | 2009-05-12 | Masimo Corporation | Remote sensing infant warmer |
US20090054747A1 (en) * | 2005-10-31 | 2009-02-26 | Abbott Diabetes Care, Inc. | Method and system for providing analyte sensor tester isolation |
US7766829B2 (en) | 2005-11-04 | 2010-08-03 | Abbott Diabetes Care Inc. | Method and system for providing basal profile modification in analyte monitoring and management systems |
JP5049289B2 (en) | 2005-11-29 | 2012-10-17 | マシモ コーポレイション | Optical sensor including disposable and reusable elements |
WO2007065015A2 (en) * | 2005-12-03 | 2007-06-07 | Masimo Corporation | Physiological alarm notification system |
US7990382B2 (en) | 2006-01-03 | 2011-08-02 | Masimo Corporation | Virtual display |
JP5292104B2 (en) * | 2006-01-05 | 2013-09-18 | ユニバーシティ オブ バージニア パテント ファウンデーション | Computer-implemented method, system, and computer program for evaluating blood glucose variability in diabetes from self-monitoring data |
US8182443B1 (en) | 2006-01-17 | 2012-05-22 | Masimo Corporation | Drug administration controller |
US20070264130A1 (en) * | 2006-01-27 | 2007-11-15 | Phluid, Inc. | Infusion Pumps and Methods for Use |
US20070244377A1 (en) * | 2006-03-14 | 2007-10-18 | Cozad Jenny L | Pulse oximeter sleeve |
US8219172B2 (en) * | 2006-03-17 | 2012-07-10 | Glt Acquisition Corp. | System and method for creating a stable optical interface |
KR101361376B1 (en) | 2006-03-30 | 2014-02-10 | 발레리타스 인코포레이티드 | Multi-cartridge fluid delivery device |
US8226891B2 (en) | 2006-03-31 | 2012-07-24 | Abbott Diabetes Care Inc. | Analyte monitoring devices and methods therefor |
US7620438B2 (en) | 2006-03-31 | 2009-11-17 | Abbott Diabetes Care Inc. | Method and system for powering an electronic device |
US20070265513A1 (en) * | 2006-05-11 | 2007-11-15 | Schenkman Kenneth A | Optical measurement of mitochondrial function in blood perfused tissue |
US20080200780A1 (en) * | 2006-05-11 | 2008-08-21 | Schenkman Kenneth A | Optical measurement of cellular energetics |
US8998809B2 (en) * | 2006-05-15 | 2015-04-07 | Cercacor Laboratories, Inc. | Systems and methods for calibrating minimally invasive and non-invasive physiological sensor devices |
US7941199B2 (en) | 2006-05-15 | 2011-05-10 | Masimo Laboratories, Inc. | Sepsis monitor |
US9176141B2 (en) | 2006-05-15 | 2015-11-03 | Cercacor Laboratories, Inc. | Physiological monitor calibration system |
US8126554B2 (en) * | 2006-05-17 | 2012-02-28 | Cardiac Pacemakers, Inc. | Implantable medical device with chemical sensor and related methods |
WO2007140478A2 (en) | 2006-05-31 | 2007-12-06 | Masimo Corporation | Respiratory monitoring |
US20090054749A1 (en) * | 2006-05-31 | 2009-02-26 | Abbott Diabetes Care, Inc. | Method and System for Providing Data Transmission in a Data Management System |
US10188348B2 (en) | 2006-06-05 | 2019-01-29 | Masimo Corporation | Parameter upgrade system |
US20080064937A1 (en) * | 2006-06-07 | 2008-03-13 | Abbott Diabetes Care, Inc. | Analyte monitoring system and method |
US7381972B1 (en) | 2006-07-24 | 2008-06-03 | Science Applications International Corporation | System and method for light fluorescence detection |
US7486976B1 (en) | 2006-07-25 | 2009-02-03 | Edward Belotserkovsky | Optical non-invasive blood monitoring system and method |
US8326390B2 (en) * | 2006-07-25 | 2012-12-04 | Edward Belotserkovsky | Optical non-invasive blood monitoring system and method |
US8126527B2 (en) * | 2006-08-03 | 2012-02-28 | University Of Washington Through Its Center For Commercialization | Method and system for determining the contribution of hemoglobin and myoglobin to in vivo optical spectra |
US20080064965A1 (en) * | 2006-09-08 | 2008-03-13 | Jay Gregory D | Devices and methods for measuring pulsus paradoxus |
USD609193S1 (en) | 2007-10-12 | 2010-02-02 | Masimo Corporation | Connector assembly |
US8457707B2 (en) | 2006-09-20 | 2013-06-04 | Masimo Corporation | Congenital heart disease monitor |
USD614305S1 (en) | 2008-02-29 | 2010-04-20 | Masimo Corporation | Connector assembly |
US8315683B2 (en) * | 2006-09-20 | 2012-11-20 | Masimo Corporation | Duo connector patient cable |
US20080103375A1 (en) * | 2006-09-22 | 2008-05-01 | Kiani Massi E | Patient monitor user interface |
US9161696B2 (en) | 2006-09-22 | 2015-10-20 | Masimo Corporation | Modular patient monitor |
US8840549B2 (en) * | 2006-09-22 | 2014-09-23 | Masimo Corporation | Modular patient monitor |
US8265723B1 (en) | 2006-10-12 | 2012-09-11 | Cercacor Laboratories, Inc. | Oximeter probe off indicator defining probe off space |
US8255026B1 (en) | 2006-10-12 | 2012-08-28 | Masimo Corporation, Inc. | Patient monitor capable of monitoring the quality of attached probes and accessories |
US9192329B2 (en) | 2006-10-12 | 2015-11-24 | Masimo Corporation | Variable mode pulse indicator |
US7880626B2 (en) | 2006-10-12 | 2011-02-01 | Masimo Corporation | System and method for monitoring the life of a physiological sensor |
WO2008045538A2 (en) | 2006-10-12 | 2008-04-17 | Masimo Corporation | Perfusion index smoother |
US20080094228A1 (en) * | 2006-10-12 | 2008-04-24 | Welch James P | Patient monitor using radio frequency identification tags |
US9861305B1 (en) | 2006-10-12 | 2018-01-09 | Masimo Corporation | Method and apparatus for calibration to reduce coupling between signals in a measurement system |
US8600467B2 (en) | 2006-11-29 | 2013-12-03 | Cercacor Laboratories, Inc. | Optical sensor including disposable and reusable elements |
WO2008073855A2 (en) * | 2006-12-09 | 2008-06-19 | Masimo Corporation | Plethysmograph variability processor |
US8852094B2 (en) | 2006-12-22 | 2014-10-07 | Masimo Corporation | Physiological parameter system |
US7791155B2 (en) * | 2006-12-22 | 2010-09-07 | Masimo Laboratories, Inc. | Detector shield |
US20080177659A1 (en) * | 2007-01-19 | 2008-07-24 | Timothy Douglas Lacey | Systems and methods for providing financial processing in conjunction with instant messaging and other communications |
US8652060B2 (en) | 2007-01-20 | 2014-02-18 | Masimo Corporation | Perfusion trend indicator |
US8930203B2 (en) | 2007-02-18 | 2015-01-06 | Abbott Diabetes Care Inc. | Multi-function analyte test device and methods therefor |
US8732188B2 (en) | 2007-02-18 | 2014-05-20 | Abbott Diabetes Care Inc. | Method and system for providing contextual based medication dosage determination |
US8123686B2 (en) | 2007-03-01 | 2012-02-28 | Abbott Diabetes Care Inc. | Method and apparatus for providing rolling data in communication systems |
US20090093687A1 (en) * | 2007-03-08 | 2009-04-09 | Telfort Valery G | Systems and methods for determining a physiological condition using an acoustic monitor |
US20080228056A1 (en) | 2007-03-13 | 2008-09-18 | Michael Blomquist | Basal rate testing using frequent blood glucose input |
US8781544B2 (en) * | 2007-03-27 | 2014-07-15 | Cercacor Laboratories, Inc. | Multiple wavelength optical sensor |
US8374665B2 (en) | 2007-04-21 | 2013-02-12 | Cercacor Laboratories, Inc. | Tissue profile wellness monitor |
US8456301B2 (en) | 2007-05-08 | 2013-06-04 | Abbott Diabetes Care Inc. | Analyte monitoring system and methods |
US8665091B2 (en) | 2007-05-08 | 2014-03-04 | Abbott Diabetes Care Inc. | Method and device for determining elapsed sensor life |
US7928850B2 (en) | 2007-05-08 | 2011-04-19 | Abbott Diabetes Care Inc. | Analyte monitoring system and methods |
US20080281179A1 (en) * | 2007-05-08 | 2008-11-13 | Abbott Diabetes Care, Inc. | Analyte monitoring system and methods |
US8461985B2 (en) * | 2007-05-08 | 2013-06-11 | Abbott Diabetes Care Inc. | Analyte monitoring system and methods |
US7751907B2 (en) | 2007-05-24 | 2010-07-06 | Smiths Medical Asd, Inc. | Expert system for insulin pump therapy |
US8221345B2 (en) | 2007-05-30 | 2012-07-17 | Smiths Medical Asd, Inc. | Insulin pump based expert system |
US7873397B2 (en) | 2007-06-19 | 2011-01-18 | Richard Higgins | Spectroscopic optical system |
US8764671B2 (en) | 2007-06-28 | 2014-07-01 | Masimo Corporation | Disposable active pulse sensor |
US8048040B2 (en) | 2007-09-13 | 2011-11-01 | Masimo Corporation | Fluid titration system |
US8355766B2 (en) * | 2007-10-12 | 2013-01-15 | Masimo Corporation | Ceramic emitter substrate |
WO2009049101A1 (en) * | 2007-10-12 | 2009-04-16 | Masimo Corporation | Connector assembly |
US8310336B2 (en) * | 2008-10-10 | 2012-11-13 | Masimo Corporation | Systems and methods for storing, analyzing, retrieving and displaying streaming medical data |
US8274360B2 (en) | 2007-10-12 | 2012-09-25 | Masimo Corporation | Systems and methods for storing, analyzing, and retrieving medical data |
US20090247984A1 (en) * | 2007-10-24 | 2009-10-01 | Masimo Laboratories, Inc. | Use of microneedles for small molecule metabolite reporter delivery |
US20090177147A1 (en) | 2008-01-07 | 2009-07-09 | Michael Blomquist | Insulin pump with insulin therapy coaching |
US8986253B2 (en) * | 2008-01-25 | 2015-03-24 | Tandem Diabetes Care, Inc. | Two chamber pumps and related methods |
US8571617B2 (en) | 2008-03-04 | 2013-10-29 | Glt Acquisition Corp. | Flowometry in optical coherence tomography for analyte level estimation |
WO2009134724A1 (en) | 2008-05-02 | 2009-11-05 | Masimo Corporation | Monitor configuration system |
EP2312995B1 (en) | 2008-05-05 | 2017-06-28 | Masimo Corporation | Pulse oximetry system with electrical decoupling circuitry |
CA2724635A1 (en) * | 2008-05-19 | 2009-11-26 | Tandem Diabetes Care, Inc. | Disposable pump reservoir and related methods |
US20100004518A1 (en) | 2008-07-03 | 2010-01-07 | Masimo Laboratories, Inc. | Heat sink for noninvasive medical sensor |
USD621516S1 (en) | 2008-08-25 | 2010-08-10 | Masimo Laboratories, Inc. | Patient monitoring sensor |
US8203438B2 (en) | 2008-07-29 | 2012-06-19 | Masimo Corporation | Alarm suspend system |
US8203704B2 (en) | 2008-08-04 | 2012-06-19 | Cercacor Laboratories, Inc. | Multi-stream sensor for noninvasive measurement of blood constituents |
SE532941C2 (en) | 2008-09-15 | 2010-05-18 | Phasein Ab | Gas sampling line for breathing gases |
US8911377B2 (en) * | 2008-09-15 | 2014-12-16 | Masimo Corporation | Patient monitor including multi-parameter graphical display |
US8408421B2 (en) | 2008-09-16 | 2013-04-02 | Tandem Diabetes Care, Inc. | Flow regulating stopcocks and related methods |
AU2009293019A1 (en) * | 2008-09-19 | 2010-03-25 | Tandem Diabetes Care Inc. | Solute concentration measurement device and related methods |
US8346330B2 (en) | 2008-10-13 | 2013-01-01 | Masimo Corporation | Reflection-detector sensor position indicator |
US8401602B2 (en) | 2008-10-13 | 2013-03-19 | Masimo Corporation | Secondary-emitter sensor position indicator |
US8771204B2 (en) | 2008-12-30 | 2014-07-08 | Masimo Corporation | Acoustic sensor assembly |
US8103456B2 (en) | 2009-01-29 | 2012-01-24 | Abbott Diabetes Care Inc. | Method and device for early signal attenuation detection using blood glucose measurements |
US8588880B2 (en) | 2009-02-16 | 2013-11-19 | Masimo Corporation | Ear sensor |
US10007758B2 (en) | 2009-03-04 | 2018-06-26 | Masimo Corporation | Medical monitoring system |
US10032002B2 (en) | 2009-03-04 | 2018-07-24 | Masimo Corporation | Medical monitoring system |
US9323894B2 (en) | 2011-08-19 | 2016-04-26 | Masimo Corporation | Health care sanitation monitoring system |
US9218454B2 (en) | 2009-03-04 | 2015-12-22 | Masimo Corporation | Medical monitoring system |
US8388353B2 (en) | 2009-03-11 | 2013-03-05 | Cercacor Laboratories, Inc. | Magnetic connector |
US20100234718A1 (en) * | 2009-03-12 | 2010-09-16 | Anand Sampath | Open architecture medical communication system |
US8897847B2 (en) | 2009-03-23 | 2014-11-25 | Masimo Corporation | Digit gauge for noninvasive optical sensor |
US9226701B2 (en) * | 2009-04-28 | 2016-01-05 | Abbott Diabetes Care Inc. | Error detection in critical repeating data in a wireless sensor system |
DE102009020252B4 (en) * | 2009-05-07 | 2012-01-12 | Krohne Optosens Gmbh | Device for measuring the fluorescence of a medium |
WO2010135373A1 (en) | 2009-05-19 | 2010-11-25 | Masimo Corporation | Disposable components for reusable physiological sensor |
US8571619B2 (en) | 2009-05-20 | 2013-10-29 | Masimo Corporation | Hemoglobin display and patient treatment |
WO2010138856A1 (en) | 2009-05-29 | 2010-12-02 | Abbott Diabetes Care Inc. | Medical device antenna systems having external antenna configurations |
US8418524B2 (en) * | 2009-06-12 | 2013-04-16 | Masimo Corporation | Non-invasive sensor calibration device |
US8670811B2 (en) * | 2009-06-30 | 2014-03-11 | Masimo Corporation | Pulse oximetry system for adjusting medical ventilation |
US20110208015A1 (en) | 2009-07-20 | 2011-08-25 | Masimo Corporation | Wireless patient monitoring system |
US20110040197A1 (en) * | 2009-07-20 | 2011-02-17 | Masimo Corporation | Wireless patient monitoring system |
US8471713B2 (en) | 2009-07-24 | 2013-06-25 | Cercacor Laboratories, Inc. | Interference detector for patient monitor |
US8473020B2 (en) | 2009-07-29 | 2013-06-25 | Cercacor Laboratories, Inc. | Non-invasive physiological sensor cover |
US20110028809A1 (en) * | 2009-07-29 | 2011-02-03 | Masimo Corporation | Patient monitor ambient display device |
US20110028806A1 (en) * | 2009-07-29 | 2011-02-03 | Sean Merritt | Reflectance calibration of fluorescence-based glucose measurements |
US9211377B2 (en) * | 2009-07-30 | 2015-12-15 | Tandem Diabetes Care, Inc. | Infusion pump system with disposable cartridge having pressure venting and pressure feedback |
US20110087081A1 (en) * | 2009-08-03 | 2011-04-14 | Kiani Massi Joe E | Personalized physiological monitor |
EP2473098A4 (en) | 2009-08-31 | 2014-04-09 | Abbott Diabetes Care Inc | Analyte signal processing device and methods |
US8993331B2 (en) | 2009-08-31 | 2015-03-31 | Abbott Diabetes Care Inc. | Analyte monitoring system and methods for managing power and noise |
US8688183B2 (en) | 2009-09-03 | 2014-04-01 | Ceracor Laboratories, Inc. | Emitter driver for noninvasive patient monitor |
US20110172498A1 (en) * | 2009-09-14 | 2011-07-14 | Olsen Gregory A | Spot check monitor credit system |
US9579039B2 (en) | 2011-01-10 | 2017-02-28 | Masimo Corporation | Non-invasive intravascular volume index monitor |
WO2011035070A1 (en) * | 2009-09-17 | 2011-03-24 | Masimo Laboratories, Inc. | Improving analyte monitoring using one or more accelerometers |
US20110137297A1 (en) | 2009-09-17 | 2011-06-09 | Kiani Massi Joe E | Pharmacological management system |
US8571618B1 (en) | 2009-09-28 | 2013-10-29 | Cercacor Laboratories, Inc. | Adaptive calibration system for spectrophotometric measurements |
EP2482720A4 (en) | 2009-09-29 | 2014-04-23 | Abbott Diabetes Care Inc | Method and apparatus for providing notification function in analyte monitoring systems |
WO2011040599A1 (en) | 2009-10-02 | 2011-04-07 | シャープ株式会社 | Device for monitoring blood vessel conditions and method for monitoring same |
US20110082711A1 (en) | 2009-10-06 | 2011-04-07 | Masimo Laboratories, Inc. | Personal digital assistant or organizer for monitoring glucose levels |
WO2011044322A1 (en) * | 2009-10-07 | 2011-04-14 | The University Of Toledo | Non-invasive ocular analyte sensing system |
US8702627B2 (en) * | 2009-10-15 | 2014-04-22 | Masimo Corporation | Acoustic respiratory monitoring sensor having multiple sensing elements |
US9106038B2 (en) | 2009-10-15 | 2015-08-11 | Masimo Corporation | Pulse oximetry system with low noise cable hub |
US10463340B2 (en) | 2009-10-15 | 2019-11-05 | Masimo Corporation | Acoustic respiratory monitoring systems and methods |
US8790268B2 (en) | 2009-10-15 | 2014-07-29 | Masimo Corporation | Bidirectional physiological information display |
US8430817B1 (en) | 2009-10-15 | 2013-04-30 | Masimo Corporation | System for determining confidence in respiratory rate measurements |
WO2011047216A2 (en) | 2009-10-15 | 2011-04-21 | Masimo Corporation | Physiological acoustic monitoring system |
US9848800B1 (en) | 2009-10-16 | 2017-12-26 | Masimo Corporation | Respiratory pause detector |
US9839381B1 (en) | 2009-11-24 | 2017-12-12 | Cercacor Laboratories, Inc. | Physiological measurement system with automatic wavelength adjustment |
DE112010004682T5 (en) | 2009-12-04 | 2013-03-28 | Masimo Corporation | Calibration for multi-level physiological monitors |
US8882701B2 (en) | 2009-12-04 | 2014-11-11 | Smiths Medical Asd, Inc. | Advanced step therapy delivery for an ambulatory infusion pump and system |
US9153112B1 (en) | 2009-12-21 | 2015-10-06 | Masimo Corporation | Modular patient monitor |
WO2011091059A1 (en) * | 2010-01-19 | 2011-07-28 | Masimo Corporation | Wellness analysis system |
WO2011109312A2 (en) * | 2010-03-01 | 2011-09-09 | Masimo Corporation | Adaptive alarm system |
US8584345B2 (en) | 2010-03-08 | 2013-11-19 | Masimo Corporation | Reprocessing of a physiological sensor |
WO2011114578A1 (en) | 2010-03-19 | 2011-09-22 | シャープ株式会社 | Measurement device, measurement method, measurement result processing device, measurement system, measurement result processing method, control program, and recording medium |
US9307928B1 (en) | 2010-03-30 | 2016-04-12 | Masimo Corporation | Plethysmographic respiration processor |
US8712494B1 (en) | 2010-05-03 | 2014-04-29 | Masimo Corporation | Reflective non-invasive sensor |
US9138180B1 (en) | 2010-05-03 | 2015-09-22 | Masimo Corporation | Sensor adapter cable |
US8666468B1 (en) | 2010-05-06 | 2014-03-04 | Masimo Corporation | Patient monitor for determining microcirculation state |
US9326712B1 (en) | 2010-06-02 | 2016-05-03 | Masimo Corporation | Opticoustic sensor |
US8740792B1 (en) | 2010-07-12 | 2014-06-03 | Masimo Corporation | Patient monitor capable of accounting for environmental conditions |
US9408542B1 (en) | 2010-07-22 | 2016-08-09 | Masimo Corporation | Non-invasive blood pressure measurement system |
WO2012027613A1 (en) | 2010-08-26 | 2012-03-01 | Masimo Corporation | Blood pressure measurement system |
JP5710767B2 (en) | 2010-09-28 | 2015-04-30 | マシモ コーポレイション | Depth of consciousness monitor including oximeter |
US9775545B2 (en) | 2010-09-28 | 2017-10-03 | Masimo Corporation | Magnetic electrical connector for patient monitors |
US9211095B1 (en) | 2010-10-13 | 2015-12-15 | Masimo Corporation | Physiological measurement logic engine |
US8723677B1 (en) | 2010-10-20 | 2014-05-13 | Masimo Corporation | Patient safety system with automatically adjusting bed |
JP2013544588A (en) | 2010-11-03 | 2013-12-19 | ユニバーシティ オブ ワシントン スルー イッツ センター フォー コマーシャライゼーション | Determination of tissue oxygenation in vivo |
US20120226117A1 (en) | 2010-12-01 | 2012-09-06 | Lamego Marcelo M | Handheld processing device including medical applications for minimally and non invasive glucose measurements |
EP3567603A1 (en) | 2011-02-13 | 2019-11-13 | Masimo Corporation | Medical risk characterization system |
US9066666B2 (en) | 2011-02-25 | 2015-06-30 | Cercacor Laboratories, Inc. | Patient monitor for monitoring microcirculation |
US8830449B1 (en) | 2011-04-18 | 2014-09-09 | Cercacor Laboratories, Inc. | Blood analysis system |
US9095316B2 (en) | 2011-04-20 | 2015-08-04 | Masimo Corporation | System for generating alarms based on alarm patterns |
US9622692B2 (en) | 2011-05-16 | 2017-04-18 | Masimo Corporation | Personal health device |
US9986919B2 (en) | 2011-06-21 | 2018-06-05 | Masimo Corporation | Patient monitoring system |
US9532722B2 (en) | 2011-06-21 | 2017-01-03 | Masimo Corporation | Patient monitoring system |
US9245668B1 (en) | 2011-06-29 | 2016-01-26 | Cercacor Laboratories, Inc. | Low noise cable providing communication between electronic sensor components and patient monitor |
US11439329B2 (en) | 2011-07-13 | 2022-09-13 | Masimo Corporation | Multiple measurement mode in a physiological sensor |
US9192351B1 (en) | 2011-07-22 | 2015-11-24 | Masimo Corporation | Acoustic respiratory monitoring sensor with probe-off detection |
US8755872B1 (en) | 2011-07-28 | 2014-06-17 | Masimo Corporation | Patient monitoring system for indicating an abnormal condition |
US8723640B2 (en) | 2011-08-16 | 2014-05-13 | Elwha Llc | Distillation of status data relating to regimen compliance responsive to the presence and absence of wireless signals relating to one or more threshold frequencies |
US9782077B2 (en) | 2011-08-17 | 2017-10-10 | Masimo Corporation | Modulated physiological sensor |
US9808188B1 (en) | 2011-10-13 | 2017-11-07 | Masimo Corporation | Robust fractional saturation determination |
JP6104920B2 (en) | 2011-10-13 | 2017-03-29 | マシモ・コーポレイション | Medical surveillance hub |
US9943269B2 (en) | 2011-10-13 | 2018-04-17 | Masimo Corporation | System for displaying medical monitoring data |
EP2765909B1 (en) | 2011-10-13 | 2019-06-26 | Masimo Corporation | Physiological acoustic monitoring system |
US9778079B1 (en) | 2011-10-27 | 2017-10-03 | Masimo Corporation | Physiological monitor gauge panel |
WO2013070794A2 (en) | 2011-11-07 | 2013-05-16 | Abbott Diabetes Care Inc. | Analyte monitoring device and methods |
US9445759B1 (en) | 2011-12-22 | 2016-09-20 | Cercacor Laboratories, Inc. | Blood glucose calibration system |
US11172890B2 (en) | 2012-01-04 | 2021-11-16 | Masimo Corporation | Automated condition screening and detection |
US9392945B2 (en) | 2012-01-04 | 2016-07-19 | Masimo Corporation | Automated CCHD screening and detection |
US12004881B2 (en) | 2012-01-04 | 2024-06-11 | Masimo Corporation | Automated condition screening and detection |
US9267572B2 (en) | 2012-02-08 | 2016-02-23 | Masimo Corporation | Cable tether system |
US10149616B2 (en) | 2012-02-09 | 2018-12-11 | Masimo Corporation | Wireless patient monitoring device |
US9480435B2 (en) | 2012-02-09 | 2016-11-01 | Masimo Corporation | Configurable patient monitoring system |
US10307111B2 (en) | 2012-02-09 | 2019-06-04 | Masimo Corporation | Patient position detection system |
WO2013148605A1 (en) | 2012-03-25 | 2013-10-03 | Masimo Corporation | Physiological monitor touchscreen interface |
WO2013158791A2 (en) | 2012-04-17 | 2013-10-24 | Masimo Corporation | Hypersaturation index |
US9180242B2 (en) | 2012-05-17 | 2015-11-10 | Tandem Diabetes Care, Inc. | Methods and devices for multiple fluid transfer |
US10542903B2 (en) | 2012-06-07 | 2020-01-28 | Masimo Corporation | Depth of consciousness monitor |
US9238100B2 (en) | 2012-06-07 | 2016-01-19 | Tandem Diabetes Care, Inc. | Device and method for training users of ambulatory medical devices |
US9697928B2 (en) | 2012-08-01 | 2017-07-04 | Masimo Corporation | Automated assembly sensor cable |
US10827961B1 (en) | 2012-08-29 | 2020-11-10 | Masimo Corporation | Physiological measurement calibration |
US9968306B2 (en) | 2012-09-17 | 2018-05-15 | Abbott Diabetes Care Inc. | Methods and apparatuses for providing adverse condition notification with enhanced wireless communication range in analyte monitoring systems |
US9955937B2 (en) | 2012-09-20 | 2018-05-01 | Masimo Corporation | Acoustic patient sensor coupler |
US9877650B2 (en) | 2012-09-20 | 2018-01-30 | Masimo Corporation | Physiological monitor with mobile computing device connectivity |
US9749232B2 (en) | 2012-09-20 | 2017-08-29 | Masimo Corporation | Intelligent medical network edge router |
US9717458B2 (en) | 2012-10-20 | 2017-08-01 | Masimo Corporation | Magnetic-flap optical sensor |
US9560996B2 (en) | 2012-10-30 | 2017-02-07 | Masimo Corporation | Universal medical system |
US9787568B2 (en) | 2012-11-05 | 2017-10-10 | Cercacor Laboratories, Inc. | Physiological test credit method |
US8843186B2 (en) | 2012-11-21 | 2014-09-23 | Folim G. Halaka | Non-invasive reagentless glucose determination |
US9693694B2 (en) | 2012-11-21 | 2017-07-04 | Folim G. Halaka | Cancer cell detection using dielectrophoretic dynamic light scattering (DDLS) spectroscopy |
US9750461B1 (en) | 2013-01-02 | 2017-09-05 | Masimo Corporation | Acoustic respiratory monitoring sensor with probe-off detection |
US9724025B1 (en) | 2013-01-16 | 2017-08-08 | Masimo Corporation | Active-pulse blood analysis system |
US9750442B2 (en) | 2013-03-09 | 2017-09-05 | Masimo Corporation | Physiological status monitor |
US10441181B1 (en) | 2013-03-13 | 2019-10-15 | Masimo Corporation | Acoustic pulse and respiration monitoring system |
US9965946B2 (en) | 2013-03-13 | 2018-05-08 | Masimo Corporation | Systems and methods for monitoring a patient health network |
WO2014158820A1 (en) | 2013-03-14 | 2014-10-02 | Cercacor Laboratories, Inc. | Patient monitor as a minimally invasive glucometer |
US9173998B2 (en) | 2013-03-14 | 2015-11-03 | Tandem Diabetes Care, Inc. | System and method for detecting occlusions in an infusion pump |
US9986952B2 (en) | 2013-03-14 | 2018-06-05 | Masimo Corporation | Heart sound simulator |
US9936917B2 (en) | 2013-03-14 | 2018-04-10 | Masimo Laboratories, Inc. | Patient monitor placement indicator |
US10456038B2 (en) | 2013-03-15 | 2019-10-29 | Cercacor Laboratories, Inc. | Cloud-based physiological monitoring system |
US9891079B2 (en) | 2013-07-17 | 2018-02-13 | Masimo Corporation | Pulser with double-bearing position encoder for non-invasive physiological monitoring |
US10555678B2 (en) | 2013-08-05 | 2020-02-11 | Masimo Corporation | Blood pressure monitor with valve-chamber assembly |
WO2015035304A1 (en) | 2013-09-06 | 2015-03-12 | Tandem Diabetes Care, Inc. | System and method for mitigating risk in automated medicament dosing |
WO2015038683A2 (en) | 2013-09-12 | 2015-03-19 | Cercacor Laboratories, Inc. | Medical device management system |
US10010276B2 (en) | 2013-10-07 | 2018-07-03 | Masimo Corporation | Regional oximetry user interface |
US11147518B1 (en) | 2013-10-07 | 2021-10-19 | Masimo Corporation | Regional oximetry signal processor |
US10832818B2 (en) | 2013-10-11 | 2020-11-10 | Masimo Corporation | Alarm notification system |
US10828007B1 (en) | 2013-10-11 | 2020-11-10 | Masimo Corporation | Acoustic sensor with attachment portion |
US10279247B2 (en) | 2013-12-13 | 2019-05-07 | Masimo Corporation | Avatar-incentive healthcare therapy |
US11259745B2 (en) | 2014-01-28 | 2022-03-01 | Masimo Corporation | Autonomous drug delivery system |
US10086138B1 (en) | 2014-01-28 | 2018-10-02 | Masimo Corporation | Autonomous drug delivery system |
US10532174B2 (en) | 2014-02-21 | 2020-01-14 | Masimo Corporation | Assistive capnography device |
US9924897B1 (en) | 2014-06-12 | 2018-03-27 | Masimo Corporation | Heated reprocessing of physiological sensors |
US10123729B2 (en) | 2014-06-13 | 2018-11-13 | Nanthealth, Inc. | Alarm fatigue management systems and methods |
US10231670B2 (en) | 2014-06-19 | 2019-03-19 | Masimo Corporation | Proximity sensor in pulse oximeter |
WO2016019133A1 (en) | 2014-07-30 | 2016-02-04 | Tandem Diabetes Care, Inc. | Temporary suspension for closed-loop medicament therapy |
US10111591B2 (en) | 2014-08-26 | 2018-10-30 | Nanthealth, Inc. | Real-time monitoring systems and methods in a healthcare environment |
WO2016036985A1 (en) | 2014-09-04 | 2016-03-10 | Masimo Corportion | Total hemoglobin index system |
US10383520B2 (en) | 2014-09-18 | 2019-08-20 | Masimo Semiconductor, Inc. | Enhanced visible near-infrared photodiode and non-invasive physiological sensor |
US10154815B2 (en) | 2014-10-07 | 2018-12-18 | Masimo Corporation | Modular physiological sensors |
AU2016209104B2 (en) | 2015-01-23 | 2020-04-30 | Masimo Sweden Ab | Nasal/oral cannula system and manufacturing |
CN107431301B (en) | 2015-02-06 | 2021-03-30 | 迈心诺公司 | Connector assembly with retractable needle for use with medical sensors |
USD755392S1 (en) | 2015-02-06 | 2016-05-03 | Masimo Corporation | Pulse oximetry sensor |
CN107405075B (en) | 2015-02-06 | 2021-03-05 | 迈心诺公司 | Folded flexible circuit for optical probe |
US10568553B2 (en) | 2015-02-06 | 2020-02-25 | Masimo Corporation | Soft boot pulse oximetry sensor |
US10524738B2 (en) | 2015-05-04 | 2020-01-07 | Cercacor Laboratories, Inc. | Noninvasive sensor system with visual infographic display |
US11653862B2 (en) | 2015-05-22 | 2023-05-23 | Cercacor Laboratories, Inc. | Non-invasive optical physiological differential pathlength sensor |
US10716500B2 (en) | 2015-06-29 | 2020-07-21 | Cardiac Pacemakers, Inc. | Systems and methods for normalization of chemical sensor data based on fluid state changes |
US10448871B2 (en) | 2015-07-02 | 2019-10-22 | Masimo Corporation | Advanced pulse oximetry sensor |
CA2994172A1 (en) | 2015-08-11 | 2017-02-16 | Masimo Corporation | Medical monitoring analysis and replay including indicia responsive to light attenuated by body tissue |
WO2017040700A2 (en) | 2015-08-31 | 2017-03-09 | Masimo Corporation | Wireless patient monitoring systems and methods |
US11504066B1 (en) | 2015-09-04 | 2022-11-22 | Cercacor Laboratories, Inc. | Low-noise sensor system |
US11679579B2 (en) | 2015-12-17 | 2023-06-20 | Masimo Corporation | Varnish-coated release liner |
US10569016B2 (en) | 2015-12-29 | 2020-02-25 | Tandem Diabetes Care, Inc. | System and method for switching between closed loop and open loop control of an ambulatory infusion pump |
US10993662B2 (en) | 2016-03-04 | 2021-05-04 | Masimo Corporation | Nose sensor |
US10537285B2 (en) | 2016-03-04 | 2020-01-21 | Masimo Corporation | Nose sensor |
US11191484B2 (en) | 2016-04-29 | 2021-12-07 | Masimo Corporation | Optical sensor tape |
US10608817B2 (en) | 2016-07-06 | 2020-03-31 | Masimo Corporation | Secure and zero knowledge data sharing for cloud applications |
US10617302B2 (en) | 2016-07-07 | 2020-04-14 | Masimo Corporation | Wearable pulse oximeter and respiration monitor |
JP7197473B2 (en) | 2016-10-13 | 2022-12-27 | マシモ・コーポレイション | System and method for patient fall detection |
US11504058B1 (en) | 2016-12-02 | 2022-11-22 | Masimo Corporation | Multi-site noninvasive measurement of a physiological parameter |
WO2018119239A1 (en) | 2016-12-22 | 2018-06-28 | Cercacor Laboratories, Inc | Methods and devices for detecting intensity of light with translucent detector |
US10721785B2 (en) | 2017-01-18 | 2020-07-21 | Masimo Corporation | Patient-worn wireless physiological sensor with pairing functionality |
US10506926B2 (en) | 2017-02-18 | 2019-12-17 | Arc Devices Limited | Multi-vital sign detector in an electronic medical records system |
US10492684B2 (en) | 2017-02-21 | 2019-12-03 | Arc Devices Limited | Multi-vital-sign smartphone system in an electronic medical records system |
WO2018156648A1 (en) | 2017-02-24 | 2018-08-30 | Masimo Corporation | Managing dynamic licenses for physiological parameters in a patient monitoring environment |
US11086609B2 (en) | 2017-02-24 | 2021-08-10 | Masimo Corporation | Medical monitoring hub |
EP4365911A3 (en) | 2017-02-24 | 2024-05-29 | Masimo Corporation | Medical device cable and method of sharing data between connected medical devices |
US10388120B2 (en) | 2017-02-24 | 2019-08-20 | Masimo Corporation | Localized projection of audible noises in medical settings |
WO2018156809A1 (en) | 2017-02-24 | 2018-08-30 | Masimo Corporation | Augmented reality system for displaying patient data |
US10327713B2 (en) | 2017-02-24 | 2019-06-25 | Masimo Corporation | Modular multi-parameter patient monitoring device |
CN110891486A (en) | 2017-03-10 | 2020-03-17 | 梅西莫股份有限公司 | Pneumonia screening instrument |
WO2018194992A1 (en) | 2017-04-18 | 2018-10-25 | Masimo Corporation | Nose sensor |
US10918281B2 (en) | 2017-04-26 | 2021-02-16 | Masimo Corporation | Medical monitoring device having multiple configurations |
USD835283S1 (en) | 2017-04-28 | 2018-12-04 | Masimo Corporation | Medical monitoring device |
USD835285S1 (en) | 2017-04-28 | 2018-12-04 | Masimo Corporation | Medical monitoring device |
USD835282S1 (en) | 2017-04-28 | 2018-12-04 | Masimo Corporation | Medical monitoring device |
USD835284S1 (en) | 2017-04-28 | 2018-12-04 | Masimo Corporation | Medical monitoring device |
KR102615025B1 (en) | 2017-04-28 | 2023-12-18 | 마시모 코오퍼레이션 | Spot check measurement system |
CN117373636A (en) | 2017-05-08 | 2024-01-09 | 梅西莫股份有限公司 | System for pairing a medical system with a network controller using an adapter |
CN108968976B (en) | 2017-05-31 | 2022-09-13 | 心脏起搏器股份公司 | Implantable medical device with chemical sensor |
WO2019014629A1 (en) | 2017-07-13 | 2019-01-17 | Cercacor Laboratories, Inc. | Medical monitoring device for harmonizing physiological measurements |
US12004853B2 (en) | 2017-07-26 | 2024-06-11 | Cardiac Pacemakers, Inc. | Systems and methods for disambiguation of posture |
CN109381195B (en) | 2017-08-10 | 2023-01-10 | 心脏起搏器股份公司 | Systems and methods including electrolyte sensor fusion |
US10602987B2 (en) | 2017-08-10 | 2020-03-31 | Arc Devices Limited | Multi-vital-sign smartphone system in an electronic medical records system |
USD890708S1 (en) | 2017-08-15 | 2020-07-21 | Masimo Corporation | Connector |
USD906970S1 (en) | 2017-08-15 | 2021-01-05 | Masimo Corporation | Connector |
USD880477S1 (en) | 2017-08-15 | 2020-04-07 | Masimo Corporation | Connector |
EP3668394A1 (en) | 2017-08-15 | 2020-06-24 | Masimo Corporation | Water resistant connector for noninvasive patient monitor |
CN109419515B (en) | 2017-08-23 | 2023-03-24 | 心脏起搏器股份公司 | Implantable chemical sensor with staged activation |
EP4039177A1 (en) | 2017-10-19 | 2022-08-10 | Masimo Corporation | Display arrangement for medical monitoring system |
USD925597S1 (en) | 2017-10-31 | 2021-07-20 | Masimo Corporation | Display screen or portion thereof with graphical user interface |
US10987066B2 (en) | 2017-10-31 | 2021-04-27 | Masimo Corporation | System for displaying oxygen state indications |
CN109864746B (en) | 2017-12-01 | 2023-09-29 | 心脏起搏器股份公司 | Multimode analyte sensor for medical devices |
CN109864747B (en) | 2017-12-05 | 2023-08-25 | 心脏起搏器股份公司 | Multimode analyte sensor optoelectronic interface |
US11766198B2 (en) | 2018-02-02 | 2023-09-26 | Cercacor Laboratories, Inc. | Limb-worn patient monitoring device |
EP3782165A1 (en) | 2018-04-19 | 2021-02-24 | Masimo Corporation | Mobile patient alarm display |
WO2019209915A1 (en) | 2018-04-24 | 2019-10-31 | Cercacor Laboratories, Inc. | Easy insert finger sensor for transmission based spectroscopy sensor |
US10485431B1 (en) | 2018-05-21 | 2019-11-26 | ARC Devices Ltd. | Glucose multi-vital-sign system in an electronic medical records system |
WO2019236759A1 (en) | 2018-06-06 | 2019-12-12 | Masimo Corporation | Opioid overdose monitoring |
US10779098B2 (en) | 2018-07-10 | 2020-09-15 | Masimo Corporation | Patient monitor alarm speaker analyzer |
US11872156B2 (en) | 2018-08-22 | 2024-01-16 | Masimo Corporation | Core body temperature measurement |
USD917550S1 (en) | 2018-10-11 | 2021-04-27 | Masimo Corporation | Display screen or portion thereof with a graphical user interface |
MX2021004063A (en) | 2018-10-11 | 2021-06-04 | Masimo Corp | Patient connector assembly with vertical detents. |
US11389093B2 (en) | 2018-10-11 | 2022-07-19 | Masimo Corporation | Low noise oximetry cable |
USD998631S1 (en) | 2018-10-11 | 2023-09-12 | Masimo Corporation | Display screen or portion thereof with a graphical user interface |
USD917564S1 (en) | 2018-10-11 | 2021-04-27 | Masimo Corporation | Display screen or portion thereof with graphical user interface |
USD998630S1 (en) | 2018-10-11 | 2023-09-12 | Masimo Corporation | Display screen or portion thereof with a graphical user interface |
USD999246S1 (en) | 2018-10-11 | 2023-09-19 | Masimo Corporation | Display screen or portion thereof with a graphical user interface |
US11406286B2 (en) | 2018-10-11 | 2022-08-09 | Masimo Corporation | Patient monitoring device with improved user interface |
USD916135S1 (en) | 2018-10-11 | 2021-04-13 | Masimo Corporation | Display screen or portion thereof with a graphical user interface |
USD897098S1 (en) | 2018-10-12 | 2020-09-29 | Masimo Corporation | Card holder set |
WO2020077149A1 (en) | 2018-10-12 | 2020-04-16 | Masimo Corporation | System for transmission of sensor data using dual communication protocol |
US11464410B2 (en) | 2018-10-12 | 2022-10-11 | Masimo Corporation | Medical systems and methods |
US12004869B2 (en) | 2018-11-05 | 2024-06-11 | Masimo Corporation | System to monitor and manage patient hydration via plethysmograph variablity index in response to the passive leg raising |
US11986289B2 (en) | 2018-11-27 | 2024-05-21 | Willow Laboratories, Inc. | Assembly for medical monitoring device with multiple physiological sensors |
US11684296B2 (en) | 2018-12-21 | 2023-06-27 | Cercacor Laboratories, Inc. | Noninvasive physiological sensor |
US20200329993A1 (en) | 2019-04-17 | 2020-10-22 | Masimo Corporation | Electrocardiogram device |
USD919094S1 (en) | 2019-08-16 | 2021-05-11 | Masimo Corporation | Blood pressure device |
USD919100S1 (en) | 2019-08-16 | 2021-05-11 | Masimo Corporation | Holder for a patient monitor |
USD917704S1 (en) | 2019-08-16 | 2021-04-27 | Masimo Corporation | Patient monitor |
USD921202S1 (en) | 2019-08-16 | 2021-06-01 | Masimo Corporation | Holder for a blood pressure device |
USD985498S1 (en) | 2019-08-16 | 2023-05-09 | Masimo Corporation | Connector |
US11832940B2 (en) | 2019-08-27 | 2023-12-05 | Cercacor Laboratories, Inc. | Non-invasive medical monitoring device for blood analyte measurements |
EP4046164A1 (en) | 2019-10-18 | 2022-08-24 | Masimo Corporation | Display layout and interactive objects for patient monitoring |
USD927699S1 (en) | 2019-10-18 | 2021-08-10 | Masimo Corporation | Electrode pad |
BR112022007593A2 (en) | 2019-10-25 | 2022-08-23 | Cercacor Lab Inc | INDICATOR COMPOUNDS, DEVICES INCLUDING INDICATOR COMPOUNDS AND MANUFACTURING AND USE METHODS |
GB202001336D0 (en) * | 2020-01-31 | 2020-03-18 | Imp College Innovations Ltd | Methods for measuring gut permeability and gastric emptying rate |
EP4104037A1 (en) | 2020-02-13 | 2022-12-21 | Masimo Corporation | System and method for monitoring clinical activities |
US11879960B2 (en) | 2020-02-13 | 2024-01-23 | Masimo Corporation | System and method for monitoring clinical activities |
KR20220159408A (en) | 2020-03-20 | 2022-12-02 | 마시모 코오퍼레이션 | Wearable device for non-invasive body temperature measurement |
USD933232S1 (en) | 2020-05-11 | 2021-10-12 | Masimo Corporation | Blood pressure monitor |
USD979516S1 (en) | 2020-05-11 | 2023-02-28 | Masimo Corporation | Connector |
WO2021247300A1 (en) | 2020-06-01 | 2021-12-09 | Arc Devices Limited | Apparatus and methods for measuring blood pressure and other vital signs via a finger |
USD980091S1 (en) | 2020-07-27 | 2023-03-07 | Masimo Corporation | Wearable temperature measurement device |
USD974193S1 (en) | 2020-07-27 | 2023-01-03 | Masimo Corporation | Wearable temperature measurement device |
US11986067B2 (en) | 2020-08-19 | 2024-05-21 | Masimo Corporation | Strap for a wearable device |
USD946597S1 (en) | 2020-09-30 | 2022-03-22 | Masimo Corporation | Display screen or portion thereof with graphical user interface |
USD946596S1 (en) | 2020-09-30 | 2022-03-22 | Masimo Corporation | Display screen or portion thereof with graphical user interface |
USD946598S1 (en) | 2020-09-30 | 2022-03-22 | Masimo Corporation | Display screen or portion thereof with graphical user interface |
USD997365S1 (en) | 2021-06-24 | 2023-08-29 | Masimo Corporation | Physiological nose sensor |
USD1000975S1 (en) | 2021-09-22 | 2023-10-10 | Masimo Corporation | Wearable temperature measurement device |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1993017621A1 (en) * | 1992-03-12 | 1993-09-16 | Wong Jacob Y | Blood chemistry measurement by stimulated infrared emission |
WO1997048331A1 (en) * | 1996-06-19 | 1997-12-24 | Board Of Regents, The University Of Texas System | Method and apparatus for diagnosing squamous intraepithelial lesions of the cervix using fluorescence spectroscopy |
WO1999027848A1 (en) * | 1997-12-02 | 1999-06-10 | Abbott Laboratories | Multiplex sensor and method of use |
WO1999051142A2 (en) * | 1998-04-06 | 1999-10-14 | The General Hospital Corporation | Non-invasive tissue glucose level monitoring |
Family Cites Families (62)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3837339A (en) | 1972-02-03 | 1974-09-24 | Whittaker Corp | Blood glucose level monitoring-alarm system and method therefor |
FR2387659A1 (en) | 1977-04-21 | 1978-11-17 | Armines | GLYCEMIA CONTROL AND REGULATION DEVICE |
US4515165A (en) | 1980-02-04 | 1985-05-07 | Energy Conversion Devices, Inc. | Apparatus and method for detecting tumors |
EP0063431B1 (en) | 1981-04-10 | 1987-10-28 | Masaaki Konomi | Spectroscopic analyzer system |
US5140989A (en) | 1983-10-14 | 1992-08-25 | Somanetics Corporation | Examination instrument for optical-response diagnostic apparatus |
US5202424A (en) | 1984-03-19 | 1993-04-13 | The Rockefeller University | Mesangial cell-derived receptors for advanced glycosylation endproducts and uses thereof |
US4655225A (en) | 1985-04-18 | 1987-04-07 | Kurabo Industries Ltd. | Spectrophotometric method and apparatus for the non-invasive |
US4680268A (en) | 1985-09-18 | 1987-07-14 | Children's Hospital Medical Center | Implantable gas-containing biosensor and method for measuring an analyte such as glucose |
US5001054A (en) | 1986-06-26 | 1991-03-19 | Becton, Dickinson And Company | Method for monitoring glucose |
US5009230A (en) | 1988-05-31 | 1991-04-23 | Eol, Inc. | Personal glucose monitor |
US5353799A (en) | 1991-01-22 | 1994-10-11 | Non Invasive Technology, Inc. | Examination of subjects using photon migration with high directionality techniques |
SE8900612D0 (en) | 1989-02-22 | 1989-02-22 | Jonas Johansson | TISSUE CHARACTERIZATION USING A BLOOD-FREE FLUORESCENCE CRITERIA |
US5902235A (en) | 1989-03-29 | 1999-05-11 | Somanetics Corporation | Optical cerebral oximeter |
US5139023A (en) | 1989-06-02 | 1992-08-18 | Theratech Inc. | Apparatus and method for noninvasive blood glucose monitoring |
US4979509A (en) | 1989-07-19 | 1990-12-25 | Northstar Research Institute, Ltd. | Continuous glucose monitoring and a system utilized therefor |
US5101814A (en) | 1989-08-11 | 1992-04-07 | Palti Yoram Prof | System for monitoring and controlling blood glucose |
US5190041A (en) | 1989-08-11 | 1993-03-02 | Palti Yoram Prof | System for monitoring and controlling blood glucose |
US5342789A (en) | 1989-12-14 | 1994-08-30 | Sensor Technologies, Inc. | Method and device for detecting and quantifying glucose in body fluids |
US5070874A (en) | 1990-01-30 | 1991-12-10 | Biocontrol Technology, Inc. | Non-invasive determination of glucose concentration in body of patients |
US5845639A (en) | 1990-08-10 | 1998-12-08 | Board Of Regents Of The University Of Washington | Optical imaging methods |
US5209231A (en) | 1990-11-02 | 1993-05-11 | University Of Connecticut | Optical glucose sensor apparatus and method |
CA2104960C (en) | 1991-02-26 | 2005-04-05 | Richard P. Rava | Systems and methods of molecular spectroscopy to provide for the diagnosis of tissue |
US5318023A (en) | 1991-04-03 | 1994-06-07 | Cedars-Sinai Medical Center | Apparatus and method of use for a photosensitizer enhanced fluorescence based biopsy needle |
US5377676A (en) | 1991-04-03 | 1995-01-03 | Cedars-Sinai Medical Center | Method for determining the biodistribution of substances using fluorescence spectroscopy |
CA2126227C (en) | 1991-12-17 | 2001-10-23 | Eduard Emmanuilovich Godik | Method of living system organism diagnostics and apparatus for its realization |
US5624804A (en) | 1991-12-20 | 1997-04-29 | The Rockefeller University | Immunochemical detection of In vivo advanced glycosylation end products |
WO1993012712A1 (en) | 1991-12-31 | 1993-07-08 | Vivascan Corporation | Blood constituent determination based on differential spectral analysis |
US5452716A (en) | 1992-02-25 | 1995-09-26 | Novo Nordisk A/S | Method and device for in vivo measuring the concentration of a substance in the blood |
US5853370A (en) | 1996-09-13 | 1998-12-29 | Non-Invasive Technology, Inc. | Optical system and method for non-invasive imaging of biological tissue |
DE4320579C2 (en) | 1992-06-15 | 2000-06-15 | Topcon Corp | Surgical microscope |
US5672875A (en) | 1992-07-15 | 1997-09-30 | Optix Lp | Methods of minimizing scattering and improving tissue sampling in non-invasive testing and imaging |
US5818048A (en) | 1992-07-15 | 1998-10-06 | Optix Lp | Rapid non-invasive optical analysis using broad bandpass spectral processing |
US5434412A (en) | 1992-07-15 | 1995-07-18 | Myron J. Block | Non-spectrophotometric measurement of analyte concentrations and optical properties of objects |
US6222189B1 (en) | 1992-07-15 | 2001-04-24 | Optix, Lp | Methods of enhancing optical signals by mechanical manipulation in non-invasive testing |
IL107396A (en) | 1992-11-09 | 1997-02-18 | Boehringer Mannheim Gmbh | Method and apparatus for analytical determination of glucose in a biological matrix |
US5313941A (en) | 1993-01-28 | 1994-05-24 | Braig James R | Noninvasive pulsed infrared spectrophotometer |
US5515847A (en) | 1993-01-28 | 1996-05-14 | Optiscan, Inc. | Self-emission noninvasive infrared spectrophotometer |
US5341805A (en) | 1993-04-06 | 1994-08-30 | Cedars-Sinai Medical Center | Glucose fluorescence monitor and method |
AU6186494A (en) | 1993-05-07 | 1994-11-10 | Diasense, Inc. | Non-invasive determination of analyte concentration using non-continuous radiation |
US5460177A (en) | 1993-05-07 | 1995-10-24 | Diasense, Inc. | Method for non-invasive measurement of concentration of analytes in blood using continuous spectrum radiation |
US5533509A (en) | 1993-08-12 | 1996-07-09 | Kurashiki Boseki Kabushiki Kaisha | Method and apparatus for non-invasive measurement of blood sugar level |
AU7828694A (en) | 1993-08-24 | 1995-03-22 | Mark R. Robinson | A robust accurate non-invasive analyte monitor |
US5497772A (en) | 1993-11-19 | 1996-03-12 | Alfred E. Mann Foundation For Scientific Research | Glucose monitoring system |
US5553616A (en) | 1993-11-30 | 1996-09-10 | Florida Institute Of Technology | Determination of concentrations of biological substances using raman spectroscopy and artificial neural network discriminator |
US5492118A (en) | 1993-12-16 | 1996-02-20 | Board Of Trustees Of The University Of Illinois | Determining material concentrations in tissues |
US5536249A (en) | 1994-03-09 | 1996-07-16 | Visionary Medical Products, Inc. | Pen-type injector with a microprocessor and blood characteristic monitor |
DE4415896A1 (en) | 1994-05-05 | 1995-11-09 | Boehringer Mannheim Gmbh | Analysis system for monitoring the concentration of an analyte in the blood of a patient |
DE4427101A1 (en) | 1994-07-30 | 1996-02-01 | Boehringer Mannheim Gmbh | Apparatus and method for the optical characterization of the structure and composition of a scattering sample |
US5599717A (en) | 1994-09-02 | 1997-02-04 | Martin Marietta Energy Systems, Inc. | Advanced synchronous luminescence system |
US5517313A (en) | 1995-02-21 | 1996-05-14 | Colvin, Jr.; Arthur E. | Fluorescent optical sensor |
IL113333A (en) | 1995-04-11 | 2001-01-28 | Yoav Paltieli | Optical-fiber type endoscope |
US5999836A (en) | 1995-06-06 | 1999-12-07 | Nelson; Robert S. | Enhanced high resolution breast imaging device and method utilizing non-ionizing radiation of narrow spectral bandwidth |
US6032070A (en) | 1995-06-07 | 2000-02-29 | University Of Arkansas | Method and apparatus for detecting electro-magnetic reflection from biological tissue |
US5657754A (en) | 1995-07-10 | 1997-08-19 | Rosencwaig; Allan | Apparatus for non-invasive analyses of biological compounds |
ZA967500B (en) | 1995-12-21 | 1998-03-05 | Unilever Plc | Device for the identification of acne, microcomedones, and bacteria on human skin. |
EP0955867A1 (en) | 1996-02-23 | 1999-11-17 | Diasense, Inc. | Method and apparatus for non-invasive blood glucose sensing |
US5713353A (en) | 1996-04-19 | 1998-02-03 | Castano; Jaime A. | Optical method and device for determining blood glucose levels |
US5666956A (en) | 1996-05-20 | 1997-09-16 | Buchert; Janusz Michal | Instrument and method for non-invasive monitoring of human tissue analyte by measuring the body's infrared radiation |
US5879294A (en) | 1996-06-28 | 1999-03-09 | Hutchinson Technology Inc. | Tissue chromophore measurement system |
US5921926A (en) | 1997-07-28 | 1999-07-13 | University Of Central Florida | Three dimensional optical imaging colposcopy |
EP1037553B1 (en) * | 1997-11-12 | 2007-01-24 | Lightouch Medical, Inc. | Method for non-invasive measurement of an analyte |
US6002953A (en) | 1998-05-06 | 1999-12-14 | Optix Lp | Non-invasive IR transmission measurement of analyte in the tympanic membrane |
-
1999
- 1999-04-06 US US09/287,486 patent/US6505059B1/en not_active Expired - Fee Related
-
2001
- 2001-02-20 WO PCT/US2001/005323 patent/WO2001060248A1/en not_active Application Discontinuation
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1993017621A1 (en) * | 1992-03-12 | 1993-09-16 | Wong Jacob Y | Blood chemistry measurement by stimulated infrared emission |
WO1997048331A1 (en) * | 1996-06-19 | 1997-12-24 | Board Of Regents, The University Of Texas System | Method and apparatus for diagnosing squamous intraepithelial lesions of the cervix using fluorescence spectroscopy |
WO1999027848A1 (en) * | 1997-12-02 | 1999-06-10 | Abbott Laboratories | Multiplex sensor and method of use |
WO1999051142A2 (en) * | 1998-04-06 | 1999-10-14 | The General Hospital Corporation | Non-invasive tissue glucose level monitoring |
Non-Patent Citations (1)
Title |
---|
SCHWARTZ JON A ET AL: "Diagnostic potential of laser-induced autofluorescence emission in brain tissue", JOURNAL OF KOREAN MEDICAL SCIENCE, vol. 12, no. 2, April 1997 (1997-04-01), pages 135 - 142, XP002170043 * |
Cited By (47)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US10478108B2 (en) | 1998-04-30 | 2019-11-19 | Abbott Diabetes Care Inc. | Analyte monitoring device and methods of use |
US8974386B2 (en) | 1998-04-30 | 2015-03-10 | Abbott Diabetes Care Inc. | Analyte monitoring device and methods of use |
US9014773B2 (en) | 1998-04-30 | 2015-04-21 | Abbott Diabetes Care Inc. | Analyte monitoring device and methods of use |
US9066697B2 (en) | 1998-04-30 | 2015-06-30 | Abbott Diabetes Care Inc. | Analyte monitoring device and methods of use |
US9011331B2 (en) | 1998-04-30 | 2015-04-21 | Abbott Diabetes Care Inc. | Analyte monitoring device and methods of use |
US8880137B2 (en) | 1998-04-30 | 2014-11-04 | Abbott Diabetes Care Inc. | Analyte monitoring device and methods of use |
US9066694B2 (en) | 1998-04-30 | 2015-06-30 | Abbott Diabetes Care Inc. | Analyte monitoring device and methods of use |
US9066695B2 (en) | 1998-04-30 | 2015-06-30 | Abbott Diabetes Care Inc. | Analyte monitoring device and methods of use |
US9072477B2 (en) | 1998-04-30 | 2015-07-07 | Abbott Diabetes Care Inc. | Analyte monitoring device and methods of use |
US7061593B2 (en) | 2001-11-08 | 2006-06-13 | Optiscan Biomedical Corp. | Device and method for in vitro determination of analyte concentrations within body fluids |
WO2003039362A1 (en) * | 2001-11-08 | 2003-05-15 | Optiscan Biomedical Corporation | Reagent-less whole-blood glucose meter |
AU2002356913B2 (en) * | 2001-11-08 | 2006-09-28 | Optiscan Biomedical Corporation | Reagent-less whole-blood glucose meter |
US7050157B2 (en) | 2001-11-08 | 2006-05-23 | Optiscan Biomedical Corp. | Reagent-less whole-blood glucose meter |
US6989891B2 (en) | 2001-11-08 | 2006-01-24 | Optiscan Biomedical Corporation | Device and method for in vitro determination of analyte concentrations within body fluids |
US6958809B2 (en) | 2001-11-08 | 2005-10-25 | Optiscan Biomedical Corporation | Reagent-less whole-blood glucose meter |
JP2007521072A (en) * | 2003-06-19 | 2007-08-02 | センサー テクノロジーズ リミティド ライアビリティー カンパニー | System, device and method for detecting a specimen by operating a sensor |
CN1299646C (en) * | 2004-05-21 | 2007-02-14 | 天津大学 | Optical-circuit-variable time-domain light-dividing differential wave length spectrometer for detecting tissue content and detection method thereof |
CN1297232C (en) * | 2004-05-21 | 2007-01-31 | 天津大学 | Optical-circuit-variable airspace light-dividing differencial wavelength spectometer for detecting tissue content and detection method thereof |
US9913604B2 (en) | 2005-02-14 | 2018-03-13 | Optiscan Biomedical Corporation | Analyte detection systems and methods using multiple measurements |
US10201301B2 (en) | 2005-11-01 | 2019-02-12 | Abbott Diabetes Care Inc. | Analyte monitoring device and methods of use |
US11103165B2 (en) | 2005-11-01 | 2021-08-31 | Abbott Diabetes Care Inc. | Analyte monitoring device and methods of use |
US8920319B2 (en) | 2005-11-01 | 2014-12-30 | Abbott Diabetes Care Inc. | Analyte monitoring device and methods of use |
US8915850B2 (en) | 2005-11-01 | 2014-12-23 | Abbott Diabetes Care Inc. | Analyte monitoring device and methods of use |
US11911151B1 (en) | 2005-11-01 | 2024-02-27 | Abbott Diabetes Care Inc. | Analyte monitoring device and methods of use |
US11399748B2 (en) | 2005-11-01 | 2022-08-02 | Abbott Diabetes Care Inc. | Analyte monitoring device and methods of use |
US11363975B2 (en) | 2005-11-01 | 2022-06-21 | Abbott Diabetes Care Inc. | Analyte monitoring device and methods of use |
US9078607B2 (en) | 2005-11-01 | 2015-07-14 | Abbott Diabetes Care Inc. | Analyte monitoring device and methods of use |
US11272867B2 (en) | 2005-11-01 | 2022-03-15 | Abbott Diabetes Care Inc. | Analyte monitoring device and methods of use |
US9326716B2 (en) | 2005-11-01 | 2016-05-03 | Abbott Diabetes Care Inc. | Analyte monitoring device and methods of use |
US10952652B2 (en) | 2005-11-01 | 2021-03-23 | Abbott Diabetes Care Inc. | Analyte monitoring device and methods of use |
US10231654B2 (en) | 2005-11-01 | 2019-03-19 | Abbott Diabetes Care Inc. | Analyte monitoring device and methods of use |
US8838195B2 (en) | 2007-02-06 | 2014-09-16 | Medtronic Minimed, Inc. | Optical systems and methods for ratiometric measurement of blood glucose concentration |
US9839378B2 (en) | 2007-02-06 | 2017-12-12 | Medtronic Minimed, Inc. | Optical systems and methods for ratiometric measurement of blood glucose concentration |
EP2182848A4 (en) * | 2007-08-31 | 2013-09-25 | Abbott Diabetes Care Inc | Analyte monitoring device and methods of use |
EP2182848A1 (en) * | 2007-08-31 | 2010-05-12 | Abbott Diabetes Care, Inc. | Analyte monitoring device and methods of use |
US8979790B2 (en) | 2007-11-21 | 2015-03-17 | Medtronic Minimed, Inc. | Use of an equilibrium sensor to monitor glucose concentration |
KR20140075794A (en) * | 2011-11-14 | 2014-06-19 | 에프. 호프만-라 로슈 아게 | Analytical apparatus for detecting at least one analyte in a sample |
KR101669739B1 (en) | 2011-11-14 | 2016-10-27 | 에프. 호프만-라 로슈 아게 | Analytical apparatus for detecting at least one analyte in a sample |
US9611504B2 (en) | 2011-11-14 | 2017-04-04 | Roche Diabetes Care, Inc. | Methods of measuring analytes that include a test element quality measurement based upon intrinsic luminescence of a test chemical of the test element |
WO2013072275A1 (en) * | 2011-11-14 | 2013-05-23 | Roche Diagnostics Gmbh | Analytical apparatus for detecting at least one analyte in a sample |
CN103196874A (en) * | 2012-01-09 | 2013-07-10 | 纳米及先进材料研发院有限公司 | Aggregation-induced emission (AIE) illuminant Cbased urine protein detection device for monitoring health of people |
US9155473B2 (en) | 2012-03-21 | 2015-10-13 | Korea Electrotechnology Research Institute | Reflection detection type measurement apparatus for skin autofluorescence |
US11369319B2 (en) | 2016-03-29 | 2022-06-28 | Roche Diabetes Care, Inc. | Method of operating a receiver for receiving analyte data, receiver and computer program product |
US11230727B2 (en) | 2016-10-05 | 2022-01-25 | Roche Diabetes Care, Inc. | Detection reagents and electrode arrangements for multi-analyte diagnostic test elements, as well as methods of using the same |
US11583227B2 (en) | 2018-11-11 | 2023-02-21 | Biobeat Technologies Ltd. | Wearable apparatus and method for monitoring medical properties |
CN113310957A (en) * | 2021-05-19 | 2021-08-27 | 江南大学 | Method for detecting flavoprotein by using three-dimensional fluorescence spectrum |
US12024735B2 (en) | 2021-12-10 | 2024-07-02 | Roche Diabetes Care, Inc. | Detection reagents and electrode arrangements for multi-analyte diagnostic test elements, as well as methods of using the same |
Also Published As
Publication number | Publication date |
---|---|
US6505059B1 (en) | 2003-01-07 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US6721582B2 (en) | Non-invasive tissue glucose level monitoring | |
US7899518B2 (en) | Non-invasive tissue glucose level monitoring | |
US6505059B1 (en) | Non-invasive tissue glucose level monitoring | |
US6728560B2 (en) | Non-invasive tissue glucose level monitoring | |
AU766166B2 (en) | Non-invasive tissue glucose level monitoring | |
US20020091324A1 (en) | Non-invasive tissue glucose level monitoring | |
US6741876B1 (en) | Method for determination of analytes using NIR, adjacent visible spectrum and discrete NIR wavelenths | |
EP1467652B1 (en) | Indirect measurement of tissue analytes through tissue properties | |
US6662030B2 (en) | Non-invasive sensor having controllable temperature feature | |
US20140330098A1 (en) | Reflectance calibration of fluorescence-based glucose measurements | |
AU749033B2 (en) | Apparatus and method for noninvasive glucose measurement | |
US20030144582A1 (en) | Portable non-invasive glucose monitor | |
JP2007516014A (en) | Light stimulation method and apparatus combined with glucose determination | |
JP2007175514A (en) | Implantable sensor and system for in vivo measurement and control of body fluid constituent concentration | |
CA2383725A1 (en) | Method for determination of analytes using nir, adjacent visible spectrum and discrete nir wavelengths | |
AU2001238517A1 (en) | Non-invasive tissue glucose level monitoring | |
US20070265513A1 (en) | Optical measurement of mitochondrial function in blood perfused tissue | |
Poddar et al. | Non-invasive glucose monitoring techniques: A review and current trends | |
US8126527B2 (en) | Method and system for determining the contribution of hemoglobin and myoglobin to in vivo optical spectra | |
EP1257196A1 (en) | Non-invasive tissue glucose level monitoring | |
Ali | FEASIBILITY STUDY ON DEVELOPING AN OPTICAL FIBRE-BASED, NON-INVASIVE, ELECTRO-TEXTILE SENSOR FOR DETECTING BLOOD GLUCOSE | |
Davies-Shaw et al. | New light upon non-invasive blood glucose monitoring |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AK | Designated states |
Kind code of ref document: A1 Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CR CU CZ DE DK DM DZ EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT TZ UA UG US UZ VN YU ZA ZW |
|
AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE TR BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG |
|
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
WWE | Wipo information: entry into national phase |
Ref document number: 2400309 Country of ref document: CA |
|
ENP | Entry into the national phase |
Ref country code: JP Ref document number: 2001 559349 Kind code of ref document: A Format of ref document f/p: F |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2001238517 Country of ref document: AU |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2001910962 Country of ref document: EP |
|
WWP | Wipo information: published in national office |
Ref document number: 2001910962 Country of ref document: EP |
|
REG | Reference to national code |
Ref country code: DE Ref legal event code: 8642 |
|
WWW | Wipo information: withdrawn in national office |
Ref document number: 2001910962 Country of ref document: EP |