Abstract

We demonstrate the use of Raman spectroscopy to measure the concentration of many important constituents (analytes) in serum and whole blood samples at physiological concentration in vitro across a multipatient data set. A near-infrared (830-nm) diode laser generates Raman spectra that contain superpositions of Raman signals from different analytes. Calibrations for glucose, cholesterol, urea, and other analytes are developed by use of partial least-squares cross validation. We predict six analytes in serum with significant accuracy in a 66-patient data set, using 60-s spectra. The calibrations are shown to be fairly robust against system drift over the span of seven weeks. In whole blood, a preliminary analysis yields accurate predictions of some of the same analytes and also hematocrit. The results hold promise for potential medical applications.

© 1999 Optical Society of America

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1998

R. V. Tarr, P. G. Steffes, “The noninvasive measure of d-glucose in the ocular aqueous humor using stimulated Raman spectroscopy,” IEEE/LEOS Newslett. 12(2), 22–27 (1998).

G. Small, M. Arnold, “Data handling issues for near-infrared glucose measurements,” IEEE/LEOS Newsletter 12(2), 16–17 (1998).

A. J. Berger, T.-W. Koo, I. Itzkan, M. S. Feld, “An enhanced algorithm for linear multivariate calibration,” Anal. Chem. 70, 623–628 (1998).
[CrossRef] [PubMed]

1997

J. R. Bruulsema, J. E. Hayward, T. J. Farrell, M. S. Patterson, L. Heinemann, M. Berger, T. Koschinsky, J. Sandahl-Christiansen, H. Orskov, “Correlation between blood glucose concentration in diabetics and noninvasively measured tissue optical scattering coefficient,” Opt. Lett. 22, 190–192 (1997).
[CrossRef] [PubMed]

A. J. Berger, I. Itzkan, M. S. Feld, “Feasibility of measuring blood glucose concentration by near-infrared Raman spectroscopy,” Spectrochim. Acta 53, 287–292 (1997).

G. Budínová, J. Salva, K. Volka, “Application of molecular spectroscopy in the mid-infrared region to the determination of glucose and cholesterol in whole blood and in blood serum,” Appl. Spectrosc. 51, 631–635 (1997).
[CrossRef]

K. Faber, B. R. Kowalski, “Improved prediction error estimates for multivariate calibration by correcting for the measurement error in the reference values,” Appl. Spectrosc. 51, 660–665 (1997).
[CrossRef]

A. J. Berger, M. S. Feld, “Analytical method of calculating chemometric prediction error,” Appl. Spectrosc. 51, 725–732 (1997).
[CrossRef]

F. M. Ham, I. N. Kostanic, G. M. Cohen, B. R. Gooch, “Determination of glucose concentrations in an aqueous matrix from NIR spectra using optimal time-domain filtering and partial least-squares regression,” IEEE Trans. Biomed. Eng. 44, 475–484 (1997).
[CrossRef] [PubMed]

B. D. Cameron, G. L. Coté, “Noninvasive glucose sensing utilizing a digital closed-loop polarimetric approach,” IEEE Trans. Biomed. Eng. 44, 1221–1227 (1997).
[CrossRef] [PubMed]

R. J. Erckens, M. Motamedi, W. F. March, J. P. Wicksted, “Raman spectroscopy for non-invasive characterization of ocular tissue: potential for detection of biological molecules,” J. Raman Spectrosc. 28, 293–299 (1997).
[CrossRef]

X. Dou, Y. Yamaguchi, H. Yamamoto, S. Doi, Y. Ozaki, “A highly sensitive, compact Raman system without a spectrometer for quantitative analysis of biological samples,” Vib. Spectrosc. 14, 199–205 (1997).
[CrossRef]

1996

X. Dou, Y. Yamaguchi, H. Yamamoto, S. Doi, Y. Ozaki, “Quantitative analysis of metabolites in urine using a highly precise, compact near-infrared Raman spectrometer,” Vib. Spectrosc. 13, 83–89 (1996).
[CrossRef]

G. Spanner, R. Niessner, “Noninvasive determination of blood constituents using an array of modulated laser diodes and a photoacoustic sensor head,” Fresenius J. Anal. Chem. 355, 327–328 (1996).

G. Spanner, R. Niessner, “New concept for the non-invasive determination of physiological glucose concentration using modulated laser diodes,” Fresenius J. Anal. Chem. 354, 306–310 (1996).

A. J. Berger, Y. Wang, M. S. Feld, “Rapid, noninvasive concentration measurements of aqueous biological analytes by near-infrared Raman spectroscopy,” Appl. Opt. 35, 209–212 (1996).
[CrossRef] [PubMed]

X. Dou, Y. Yamaguchi, H. Yamamoto, H. Uenoyama, Y. Ozaki, “Biological applications of anti-Stokes Raman spectroscopy: quantitative analysis of glucose in plasma and serum by a highly sensitive multichannel Raman spectrometer,” Appl. Spectrosc. 50, 1301–1306 (1996).
[CrossRef]

1995

J. P. Wicksted, R. J. Erckens, M. Motamedi, W. F. March, “Raman spectroscopy studies of metabolic concentrations in aqueous solutions and aqueous humor specimens,” Appl. Spectrosc. 49, 987–993 (1995).
[CrossRef]

A. Bittner, R. Marbach, H. M. Heise, “Multivariate calibration for protein, cholesterol and triglycerides in human plasma using short-wave near-infrared spectrometry,” J. Mol. Struct. 349, 341–344 (1995).
[CrossRef]

H. M. Heise, A. Bittner, “Investigation of experimental errors in the quantitative analysis of glucose in human blood plasma by ATR-IR spectroscopy,” J. Mol. Struct. 348, 21–24 (1995).
[CrossRef]

M. J. Goetz, G. L. Coté, R. Erckens, W. March, M. Motamedi, “Application of a multivariate technique to Raman spectra for quantification of body chemicals,” IEEE Trans. Biomed. Eng. 42, 728–731 (1995).
[CrossRef] [PubMed]

K.-U. Jagemann, C. Fischbacher, K. Danzer, U. A. Müller, B. Mertes, “Application of near-infrared spectroscopy for non-invasive determination of blood/tissue glucose using neural networks,” Z. Phys. Chem. 191, 179–190 (1995).
[CrossRef]

1994

1993

1992

D. M. Haaland, M. R. Robinson, G. W. Koepp, E. V. Thomas, R. P. Eaton, “Reagentless near-infrared determination of glucose in whole blood using multivariate calibration,” Appl. Spectrosc. 46, 1575–1578 (1992).
[CrossRef]

K. J. Ward, D. M. Haaland, M. R. Robinson, R. P. Eaton, “Post-prandial blood glucose determination by quantitative mid-infrared spectroscopy,” Appl. Spectrosc. 46, 959–965 (1992).
[CrossRef]

J. W. Hall, A. Pollard, “Near-infrared spectrophotometry: a new dimension in clinical chemistry,” Clin. Chem. 38, 1623–1631 (1992).
[PubMed]

G. L. Coté, M. D. Fox, R. B. Northrop, “Noninvasive optical polarimetric glucose sensing using a true phase measurement technique,” IEEE Trans. Biomed. Eng. 39, 752–756 (1992).
[CrossRef] [PubMed]

M. R. Robinson, R. P. Eaton, D. M. Haaland, G. W. Koepp, E. V. Thomas, B. R. Stallard, P. L. Robinson, “Noninvasive glucose monitoring in diabetic patients: a preliminary evaluation,” Clin. Chem. 38, 1618–1622 (1992).
[PubMed]

1990

M. A. Arnold, G. W. Small, “Determination of physiological levels of glucose in an aqueous matrix with digitally filtered Fourier transform near-infrared spectra,” Anal. Chem. 62, 1457–1464 (1990).
[CrossRef] [PubMed]

Y. Mendelson, A. C. Clermont, R. A. Peura, B.-C. Lin, “Blood glucose measurement by multiple attenuated total reflection and infrared absorption spectroscopy,” IEEE Trans. Biomed. Eng. 37, 458–465 (1990).
[CrossRef] [PubMed]

1988

E. Sanchez, B. R. Kowalski, “Tensorial calibration. 1. First-order calibration,” J. Chemom. 2, 247–263 (1988).
[CrossRef]

D. M. Haaland, E. V. Thomas, “Partial least-squares methods for spectral analyses. 1. Relation to other quantitative calibration methods and the extraction of qualitative information,” Anal. Chem. 60, 1193–1202 (1988).
[CrossRef]

1987

W. L. Clarke, D. Cox, L. A. Gonder-Frederick, W. Carter, S. L. Pohl, “Evaluating clinical accuracy of systems for self-monitoring of blood glucose,” Diabetes Care 10, 622–628 (1987).
[CrossRef] [PubMed]

B. Bauer, T. Floyd, “Monitoring of glucose in biological fluids by Fourier-transform infrared spectrometry with a cylindrical internal reflectance cell,” Anal. Chim. Acta 197, 295–301 (1987).
[CrossRef]

E. Peuchant, C. Salles, R. Jensen, “Determination of serum cholesterol by near-infrared reflectance spectrometry,” Anal. Chem. 59, 1816–1819 (1987).
[CrossRef] [PubMed]

1986

P. Geladi, B. R. Kowalski, “Partial least-squares regression: a tutorial,” Anal. Chim. Acta 185, 1–17 (1986).
[CrossRef]

Arnold, M.

G. Small, M. Arnold, “Data handling issues for near-infrared glucose measurements,” IEEE/LEOS Newsletter 12(2), 16–17 (1998).

Arnold, M. A.

M. A. Arnold, G. W. Small, “Determination of physiological levels of glucose in an aqueous matrix with digitally filtered Fourier transform near-infrared spectra,” Anal. Chem. 62, 1457–1464 (1990).
[CrossRef] [PubMed]

Bauer, B.

B. Bauer, T. Floyd, “Monitoring of glucose in biological fluids by Fourier-transform infrared spectrometry with a cylindrical internal reflectance cell,” Anal. Chim. Acta 197, 295–301 (1987).
[CrossRef]

Berger, A. J.

A. J. Berger, T.-W. Koo, I. Itzkan, M. S. Feld, “An enhanced algorithm for linear multivariate calibration,” Anal. Chem. 70, 623–628 (1998).
[CrossRef] [PubMed]

A. J. Berger, M. S. Feld, “Analytical method of calculating chemometric prediction error,” Appl. Spectrosc. 51, 725–732 (1997).
[CrossRef]

A. J. Berger, I. Itzkan, M. S. Feld, “Feasibility of measuring blood glucose concentration by near-infrared Raman spectroscopy,” Spectrochim. Acta 53, 287–292 (1997).

A. J. Berger, Y. Wang, M. S. Feld, “Rapid, noninvasive concentration measurements of aqueous biological analytes by near-infrared Raman spectroscopy,” Appl. Opt. 35, 209–212 (1996).
[CrossRef] [PubMed]

Berger, M.

Bittner, A.

H. M. Heise, A. Bittner, “Investigation of experimental errors in the quantitative analysis of glucose in human blood plasma by ATR-IR spectroscopy,” J. Mol. Struct. 348, 21–24 (1995).
[CrossRef]

A. Bittner, R. Marbach, H. M. Heise, “Multivariate calibration for protein, cholesterol and triglycerides in human plasma using short-wave near-infrared spectrometry,” J. Mol. Struct. 349, 341–344 (1995).
[CrossRef]

Bocker, D.

Bruulsema, J. R.

Budínová, G.

Bunimovich, D.

R. Simhi, D. Bunimovich, B.-A. Sela, A. Katzir, “Multicomponent analysis of human blood using fiberoptic evanescent wave spectroscopy,” in Medical Sensors II and Fiber Optic Sensors, F. Baldini, P. R. Coulet, A. M. Verga Scheggi, O. S. Wolfbeis, eds., Proc. SPIE2331, 166–172 (1994).
[CrossRef]

Cameron, B. D.

B. D. Cameron, G. L. Coté, “Noninvasive glucose sensing utilizing a digital closed-loop polarimetric approach,” IEEE Trans. Biomed. Eng. 44, 1221–1227 (1997).
[CrossRef] [PubMed]

Caraway, W. T.

W. T. Caraway, “Carbohydrates,” in Fundamentals of Clinical Chemistry, N. W. Tietz, ed. (Saunders, Philadelphia, Pa., 1970), pp. 154–156.

Carey, P. R.

P. R. Carey, Biochemical Applications of Raman and Resonance Raman Spectroscopies (Academic, New York, 1982), pp. 71–79.

Carter, W.

W. L. Clarke, D. Cox, L. A. Gonder-Frederick, W. Carter, S. L. Pohl, “Evaluating clinical accuracy of systems for self-monitoring of blood glucose,” Diabetes Care 10, 622–628 (1987).
[CrossRef] [PubMed]

Clarke, W. L.

W. L. Clarke, D. Cox, L. A. Gonder-Frederick, W. Carter, S. L. Pohl, “Evaluating clinical accuracy of systems for self-monitoring of blood glucose,” Diabetes Care 10, 622–628 (1987).
[CrossRef] [PubMed]

Clermont, A. C.

Y. Mendelson, A. C. Clermont, R. A. Peura, B.-C. Lin, “Blood glucose measurement by multiple attenuated total reflection and infrared absorption spectroscopy,” IEEE Trans. Biomed. Eng. 37, 458–465 (1990).
[CrossRef] [PubMed]

Cohen, G. M.

F. M. Ham, I. N. Kostanic, G. M. Cohen, B. R. Gooch, “Determination of glucose concentrations in an aqueous matrix from NIR spectra using optimal time-domain filtering and partial least-squares regression,” IEEE Trans. Biomed. Eng. 44, 475–484 (1997).
[CrossRef] [PubMed]

Cope, M.

Coté, G. L.

B. D. Cameron, G. L. Coté, “Noninvasive glucose sensing utilizing a digital closed-loop polarimetric approach,” IEEE Trans. Biomed. Eng. 44, 1221–1227 (1997).
[CrossRef] [PubMed]

M. J. Goetz, G. L. Coté, R. Erckens, W. March, M. Motamedi, “Application of a multivariate technique to Raman spectra for quantification of body chemicals,” IEEE Trans. Biomed. Eng. 42, 728–731 (1995).
[CrossRef] [PubMed]

T. W. King, G. L. Coté, R. McNichols, M. J. Goetz, “Multispectral polarimetric glucose detection using a single Pockels cell,” Opt. Eng. 33, 2746–2753 (1994).
[CrossRef]

G. L. Coté, M. D. Fox, R. B. Northrop, “Noninvasive optical polarimetric glucose sensing using a true phase measurement technique,” IEEE Trans. Biomed. Eng. 39, 752–756 (1992).
[CrossRef] [PubMed]

Cox, D.

W. L. Clarke, D. Cox, L. A. Gonder-Frederick, W. Carter, S. L. Pohl, “Evaluating clinical accuracy of systems for self-monitoring of blood glucose,” Diabetes Care 10, 622–628 (1987).
[CrossRef] [PubMed]

Danzer, K.

K.-U. Jagemann, C. Fischbacher, K. Danzer, U. A. Müller, B. Mertes, “Application of near-infrared spectroscopy for non-invasive determination of blood/tissue glucose using neural networks,” Z. Phys. Chem. 191, 179–190 (1995).
[CrossRef]

Doi, S.

X. Dou, Y. Yamaguchi, H. Yamamoto, S. Doi, Y. Ozaki, “A highly sensitive, compact Raman system without a spectrometer for quantitative analysis of biological samples,” Vib. Spectrosc. 14, 199–205 (1997).
[CrossRef]

X. Dou, Y. Yamaguchi, H. Yamamoto, S. Doi, Y. Ozaki, “Quantitative analysis of metabolites in urine using a highly precise, compact near-infrared Raman spectrometer,” Vib. Spectrosc. 13, 83–89 (1996).
[CrossRef]

Dou, X.

X. Dou, Y. Yamaguchi, H. Yamamoto, S. Doi, Y. Ozaki, “A highly sensitive, compact Raman system without a spectrometer for quantitative analysis of biological samples,” Vib. Spectrosc. 14, 199–205 (1997).
[CrossRef]

X. Dou, Y. Yamaguchi, H. Yamamoto, S. Doi, Y. Ozaki, “Quantitative analysis of metabolites in urine using a highly precise, compact near-infrared Raman spectrometer,” Vib. Spectrosc. 13, 83–89 (1996).
[CrossRef]

X. Dou, Y. Yamaguchi, H. Yamamoto, H. Uenoyama, Y. Ozaki, “Biological applications of anti-Stokes Raman spectroscopy: quantitative analysis of glucose in plasma and serum by a highly sensitive multichannel Raman spectrometer,” Appl. Spectrosc. 50, 1301–1306 (1996).
[CrossRef]

Eaton, R. P.

Erckens, R.

M. J. Goetz, G. L. Coté, R. Erckens, W. March, M. Motamedi, “Application of a multivariate technique to Raman spectra for quantification of body chemicals,” IEEE Trans. Biomed. Eng. 42, 728–731 (1995).
[CrossRef] [PubMed]

Erckens, R. J.

R. J. Erckens, M. Motamedi, W. F. March, J. P. Wicksted, “Raman spectroscopy for non-invasive characterization of ocular tissue: potential for detection of biological molecules,” J. Raman Spectrosc. 28, 293–299 (1997).
[CrossRef]

J. P. Wicksted, R. J. Erckens, M. Motamedi, W. F. March, “Raman spectroscopy studies of metabolic concentrations in aqueous solutions and aqueous humor specimens,” Appl. Spectrosc. 49, 987–993 (1995).
[CrossRef]

Essenpreis, M.

Faber, K.

Fantini, S.

Farrell, T. J.

Feld, M. S.

A. J. Berger, T.-W. Koo, I. Itzkan, M. S. Feld, “An enhanced algorithm for linear multivariate calibration,” Anal. Chem. 70, 623–628 (1998).
[CrossRef] [PubMed]

A. J. Berger, M. S. Feld, “Analytical method of calculating chemometric prediction error,” Appl. Spectrosc. 51, 725–732 (1997).
[CrossRef]

A. J. Berger, I. Itzkan, M. S. Feld, “Feasibility of measuring blood glucose concentration by near-infrared Raman spectroscopy,” Spectrochim. Acta 53, 287–292 (1997).

A. J. Berger, Y. Wang, M. S. Feld, “Rapid, noninvasive concentration measurements of aqueous biological analytes by near-infrared Raman spectroscopy,” Appl. Opt. 35, 209–212 (1996).
[CrossRef] [PubMed]

Fischbacher, C.

K.-U. Jagemann, C. Fischbacher, K. Danzer, U. A. Müller, B. Mertes, “Application of near-infrared spectroscopy for non-invasive determination of blood/tissue glucose using neural networks,” Z. Phys. Chem. 191, 179–190 (1995).
[CrossRef]

Floyd, T.

B. Bauer, T. Floyd, “Monitoring of glucose in biological fluids by Fourier-transform infrared spectrometry with a cylindrical internal reflectance cell,” Anal. Chim. Acta 197, 295–301 (1987).
[CrossRef]

Fox, M. D.

G. L. Coté, M. D. Fox, R. B. Northrop, “Noninvasive optical polarimetric glucose sensing using a true phase measurement technique,” IEEE Trans. Biomed. Eng. 39, 752–756 (1992).
[CrossRef] [PubMed]

Franceschini, M. A.

Geladi, P.

P. Geladi, B. R. Kowalski, “Partial least-squares regression: a tutorial,” Anal. Chim. Acta 185, 1–17 (1986).
[CrossRef]

Goetz, M. J.

M. J. Goetz, G. L. Coté, R. Erckens, W. March, M. Motamedi, “Application of a multivariate technique to Raman spectra for quantification of body chemicals,” IEEE Trans. Biomed. Eng. 42, 728–731 (1995).
[CrossRef] [PubMed]

T. W. King, G. L. Coté, R. McNichols, M. J. Goetz, “Multispectral polarimetric glucose detection using a single Pockels cell,” Opt. Eng. 33, 2746–2753 (1994).
[CrossRef]

Gonder-Frederick, L. A.

W. L. Clarke, D. Cox, L. A. Gonder-Frederick, W. Carter, S. L. Pohl, “Evaluating clinical accuracy of systems for self-monitoring of blood glucose,” Diabetes Care 10, 622–628 (1987).
[CrossRef] [PubMed]

Gooch, B. R.

F. M. Ham, I. N. Kostanic, G. M. Cohen, B. R. Gooch, “Determination of glucose concentrations in an aqueous matrix from NIR spectra using optimal time-domain filtering and partial least-squares regression,” IEEE Trans. Biomed. Eng. 44, 475–484 (1997).
[CrossRef] [PubMed]

Gratton, E.

Gries, F. A.

Haaland, D. M.

D. M. Haaland, M. R. Robinson, G. W. Koepp, E. V. Thomas, R. P. Eaton, “Reagentless near-infrared determination of glucose in whole blood using multivariate calibration,” Appl. Spectrosc. 46, 1575–1578 (1992).
[CrossRef]

M. R. Robinson, R. P. Eaton, D. M. Haaland, G. W. Koepp, E. V. Thomas, B. R. Stallard, P. L. Robinson, “Noninvasive glucose monitoring in diabetic patients: a preliminary evaluation,” Clin. Chem. 38, 1618–1622 (1992).
[PubMed]

K. J. Ward, D. M. Haaland, M. R. Robinson, R. P. Eaton, “Post-prandial blood glucose determination by quantitative mid-infrared spectroscopy,” Appl. Spectrosc. 46, 959–965 (1992).
[CrossRef]

D. M. Haaland, E. V. Thomas, “Partial least-squares methods for spectral analyses. 1. Relation to other quantitative calibration methods and the extraction of qualitative information,” Anal. Chem. 60, 1193–1202 (1988).
[CrossRef]

Hall, J. W.

J. W. Hall, A. Pollard, “Near-infrared spectrophotometry: a new dimension in clinical chemistry,” Clin. Chem. 38, 1623–1631 (1992).
[PubMed]

Ham, F. M.

F. M. Ham, I. N. Kostanic, G. M. Cohen, B. R. Gooch, “Determination of glucose concentrations in an aqueous matrix from NIR spectra using optimal time-domain filtering and partial least-squares regression,” IEEE Trans. Biomed. Eng. 44, 475–484 (1997).
[CrossRef] [PubMed]

Hasty, C. E.

Hayward, J. E.

Heinemann, L.

Heise, H. M.

H. M. Heise, A. Bittner, “Investigation of experimental errors in the quantitative analysis of glucose in human blood plasma by ATR-IR spectroscopy,” J. Mol. Struct. 348, 21–24 (1995).
[CrossRef]

A. Bittner, R. Marbach, H. M. Heise, “Multivariate calibration for protein, cholesterol and triglycerides in human plasma using short-wave near-infrared spectrometry,” J. Mol. Struct. 349, 341–344 (1995).
[CrossRef]

H. M. Heise, R. Marbach, T. Koschinsky, F. A. Gries, “Multicomponent assay for blood substrates in human plasma by mid-infrared spectroscopy and its evaluation for clinical analysis,” Appl. Spectrosc. 48, 85–95 (1994).
[CrossRef]

R. Marbach, T. Koschinsky, F. A. Gries, H. M. Heise, “Noninvasive blood glucose assay by near-infrared diffuse reflectance spectroscopy of the human inner lip,” Appl. Spectrosc. 47, 875–881 (1993).
[CrossRef]

Henry, R. J.

R. J. Henry, Clinical Chemistry: Principles and Techniques (Harper and Row, New York, 1964), pp. 650–651.

Itzkan, I.

A. J. Berger, T.-W. Koo, I. Itzkan, M. S. Feld, “An enhanced algorithm for linear multivariate calibration,” Anal. Chem. 70, 623–628 (1998).
[CrossRef] [PubMed]

A. J. Berger, I. Itzkan, M. S. Feld, “Feasibility of measuring blood glucose concentration by near-infrared Raman spectroscopy,” Spectrochim. Acta 53, 287–292 (1997).

Jagemann, K.-U.

K.-U. Jagemann, C. Fischbacher, K. Danzer, U. A. Müller, B. Mertes, “Application of near-infrared spectroscopy for non-invasive determination of blood/tissue glucose using neural networks,” Z. Phys. Chem. 191, 179–190 (1995).
[CrossRef]

Jensen, R.

E. Peuchant, C. Salles, R. Jensen, “Determination of serum cholesterol by near-infrared reflectance spectrometry,” Anal. Chem. 59, 1816–1819 (1987).
[CrossRef] [PubMed]

Katzir, A.

R. Simhi, D. Bunimovich, B.-A. Sela, A. Katzir, “Multicomponent analysis of human blood using fiberoptic evanescent wave spectroscopy,” in Medical Sensors II and Fiber Optic Sensors, F. Baldini, P. R. Coulet, A. M. Verga Scheggi, O. S. Wolfbeis, eds., Proc. SPIE2331, 166–172 (1994).
[CrossRef]

King, T. W.

T. W. King, G. L. Coté, R. McNichols, M. J. Goetz, “Multispectral polarimetric glucose detection using a single Pockels cell,” Opt. Eng. 33, 2746–2753 (1994).
[CrossRef]

Koepp, G. W.

D. M. Haaland, M. R. Robinson, G. W. Koepp, E. V. Thomas, R. P. Eaton, “Reagentless near-infrared determination of glucose in whole blood using multivariate calibration,” Appl. Spectrosc. 46, 1575–1578 (1992).
[CrossRef]

M. R. Robinson, R. P. Eaton, D. M. Haaland, G. W. Koepp, E. V. Thomas, B. R. Stallard, P. L. Robinson, “Noninvasive glucose monitoring in diabetic patients: a preliminary evaluation,” Clin. Chem. 38, 1618–1622 (1992).
[PubMed]

Kohl, M.

Koo, T.-W.

A. J. Berger, T.-W. Koo, I. Itzkan, M. S. Feld, “An enhanced algorithm for linear multivariate calibration,” Anal. Chem. 70, 623–628 (1998).
[CrossRef] [PubMed]

Koschinsky, T.

Kostanic, I. N.

F. M. Ham, I. N. Kostanic, G. M. Cohen, B. R. Gooch, “Determination of glucose concentrations in an aqueous matrix from NIR spectra using optimal time-domain filtering and partial least-squares regression,” IEEE Trans. Biomed. Eng. 44, 475–484 (1997).
[CrossRef] [PubMed]

Kowalski, B. R.

K. Faber, B. R. Kowalski, “Improved prediction error estimates for multivariate calibration by correcting for the measurement error in the reference values,” Appl. Spectrosc. 51, 660–665 (1997).
[CrossRef]

E. Sanchez, B. R. Kowalski, “Tensorial calibration. 1. First-order calibration,” J. Chemom. 2, 247–263 (1988).
[CrossRef]

P. Geladi, B. R. Kowalski, “Partial least-squares regression: a tutorial,” Anal. Chim. Acta 185, 1–17 (1986).
[CrossRef]

Krimm, S.

S. Krimm, “Raman spectra and the conformations of biological macromolecules,” in Biological Applications of Raman Spectroscopy, T. G. Spiro, ed. (Wiley, New York, 1987), Vol. 1, pp. 1–46.

Lin, B.-C.

Y. Mendelson, A. C. Clermont, R. A. Peura, B.-C. Lin, “Blood glucose measurement by multiple attenuated total reflection and infrared absorption spectroscopy,” IEEE Trans. Biomed. Eng. 37, 458–465 (1990).
[CrossRef] [PubMed]

Maier, J. S.

Marbach, R.

March, W.

M. J. Goetz, G. L. Coté, R. Erckens, W. March, M. Motamedi, “Application of a multivariate technique to Raman spectra for quantification of body chemicals,” IEEE Trans. Biomed. Eng. 42, 728–731 (1995).
[CrossRef] [PubMed]

March, W. F.

McNichols, R.

T. W. King, G. L. Coté, R. McNichols, M. J. Goetz, “Multispectral polarimetric glucose detection using a single Pockels cell,” Opt. Eng. 33, 2746–2753 (1994).
[CrossRef]

Mendelson, Y.

Y. Mendelson, A. C. Clermont, R. A. Peura, B.-C. Lin, “Blood glucose measurement by multiple attenuated total reflection and infrared absorption spectroscopy,” IEEE Trans. Biomed. Eng. 37, 458–465 (1990).
[CrossRef] [PubMed]

Mertes, B.

K.-U. Jagemann, C. Fischbacher, K. Danzer, U. A. Müller, B. Mertes, “Application of near-infrared spectroscopy for non-invasive determination of blood/tissue glucose using neural networks,” Z. Phys. Chem. 191, 179–190 (1995).
[CrossRef]

Motamedi, M.

R. J. Erckens, M. Motamedi, W. F. March, J. P. Wicksted, “Raman spectroscopy for non-invasive characterization of ocular tissue: potential for detection of biological molecules,” J. Raman Spectrosc. 28, 293–299 (1997).
[CrossRef]

M. J. Goetz, G. L. Coté, R. Erckens, W. March, M. Motamedi, “Application of a multivariate technique to Raman spectra for quantification of body chemicals,” IEEE Trans. Biomed. Eng. 42, 728–731 (1995).
[CrossRef] [PubMed]

J. P. Wicksted, R. J. Erckens, M. Motamedi, W. F. March, “Raman spectroscopy studies of metabolic concentrations in aqueous solutions and aqueous humor specimens,” Appl. Spectrosc. 49, 987–993 (1995).
[CrossRef]

Müller, U. A.

K.-U. Jagemann, C. Fischbacher, K. Danzer, U. A. Müller, B. Mertes, “Application of near-infrared spectroscopy for non-invasive determination of blood/tissue glucose using neural networks,” Z. Phys. Chem. 191, 179–190 (1995).
[CrossRef]

Niessner, R.

G. Spanner, R. Niessner, “New concept for the non-invasive determination of physiological glucose concentration using modulated laser diodes,” Fresenius J. Anal. Chem. 354, 306–310 (1996).

G. Spanner, R. Niessner, “Noninvasive determination of blood constituents using an array of modulated laser diodes and a photoacoustic sensor head,” Fresenius J. Anal. Chem. 355, 327–328 (1996).

Northrop, R. B.

G. L. Coté, M. D. Fox, R. B. Northrop, “Noninvasive optical polarimetric glucose sensing using a true phase measurement technique,” IEEE Trans. Biomed. Eng. 39, 752–756 (1992).
[CrossRef] [PubMed]

Orskov, H.

Ozaki, Y.

X. Dou, Y. Yamaguchi, H. Yamamoto, S. Doi, Y. Ozaki, “A highly sensitive, compact Raman system without a spectrometer for quantitative analysis of biological samples,” Vib. Spectrosc. 14, 199–205 (1997).
[CrossRef]

X. Dou, Y. Yamaguchi, H. Yamamoto, S. Doi, Y. Ozaki, “Quantitative analysis of metabolites in urine using a highly precise, compact near-infrared Raman spectrometer,” Vib. Spectrosc. 13, 83–89 (1996).
[CrossRef]

X. Dou, Y. Yamaguchi, H. Yamamoto, H. Uenoyama, Y. Ozaki, “Biological applications of anti-Stokes Raman spectroscopy: quantitative analysis of glucose in plasma and serum by a highly sensitive multichannel Raman spectrometer,” Appl. Spectrosc. 50, 1301–1306 (1996).
[CrossRef]

Patterson, M. S.

Peuchant, E.

E. Peuchant, C. Salles, R. Jensen, “Determination of serum cholesterol by near-infrared reflectance spectrometry,” Anal. Chem. 59, 1816–1819 (1987).
[CrossRef] [PubMed]

Peura, R. A.

Y. Mendelson, A. C. Clermont, R. A. Peura, B.-C. Lin, “Blood glucose measurement by multiple attenuated total reflection and infrared absorption spectroscopy,” IEEE Trans. Biomed. Eng. 37, 458–465 (1990).
[CrossRef] [PubMed]

Pohl, S. L.

W. L. Clarke, D. Cox, L. A. Gonder-Frederick, W. Carter, S. L. Pohl, “Evaluating clinical accuracy of systems for self-monitoring of blood glucose,” Diabetes Care 10, 622–628 (1987).
[CrossRef] [PubMed]

Pollard, A.

J. W. Hall, A. Pollard, “Near-infrared spectrophotometry: a new dimension in clinical chemistry,” Clin. Chem. 38, 1623–1631 (1992).
[PubMed]

Qu, J. J.

J. J. Qu, O. L. Yau, S. M. Yau, D. Suria, B. C. Wilson, “Measurements of therapeutic drugs and substances of abuse in human body fluids by near-IR laser Raman spectroscopy with new algorithms,” in Biomedical Diagnostic, Guidance, and Surgical-Assist Systems, D. A. Benaron, R. D. Bucholz, S. T. Charles, W. S. Grundfest, M. W. Vannier, T. Vo-Dinh, eds., Proc. SPIE3595, (to be published).

Robinson, M. R.

Robinson, P. L.

M. R. Robinson, R. P. Eaton, D. M. Haaland, G. W. Koepp, E. V. Thomas, B. R. Stallard, P. L. Robinson, “Noninvasive glucose monitoring in diabetic patients: a preliminary evaluation,” Clin. Chem. 38, 1618–1622 (1992).
[PubMed]

Salles, C.

E. Peuchant, C. Salles, R. Jensen, “Determination of serum cholesterol by near-infrared reflectance spectrometry,” Anal. Chem. 59, 1816–1819 (1987).
[CrossRef] [PubMed]

Salva, J.

Sanchez, E.

E. Sanchez, B. R. Kowalski, “Tensorial calibration. 1. First-order calibration,” J. Chemom. 2, 247–263 (1988).
[CrossRef]

Sandahl-Christiansen, J.

Sela, B.-A.

R. Simhi, D. Bunimovich, B.-A. Sela, A. Katzir, “Multicomponent analysis of human blood using fiberoptic evanescent wave spectroscopy,” in Medical Sensors II and Fiber Optic Sensors, F. Baldini, P. R. Coulet, A. M. Verga Scheggi, O. S. Wolfbeis, eds., Proc. SPIE2331, 166–172 (1994).
[CrossRef]

Simhi, R.

R. Simhi, D. Bunimovich, B.-A. Sela, A. Katzir, “Multicomponent analysis of human blood using fiberoptic evanescent wave spectroscopy,” in Medical Sensors II and Fiber Optic Sensors, F. Baldini, P. R. Coulet, A. M. Verga Scheggi, O. S. Wolfbeis, eds., Proc. SPIE2331, 166–172 (1994).
[CrossRef]

Skendzel, L. P.

L. P. Skendzel, “How physicians use laboratory tests,” in Using the Clinical Laboratory in Medical Decision-Making, G. D. Lundberg, ed. (American Society of Clinical Pathologists, Chicago, 1984), Chap. 30, pp. 243–250.

Small, G.

G. Small, M. Arnold, “Data handling issues for near-infrared glucose measurements,” IEEE/LEOS Newsletter 12(2), 16–17 (1998).

Small, G. W.

M. A. Arnold, G. W. Small, “Determination of physiological levels of glucose in an aqueous matrix with digitally filtered Fourier transform near-infrared spectra,” Anal. Chem. 62, 1457–1464 (1990).
[CrossRef] [PubMed]

Smith, J. W.

C. E. Speicher, J. W. Smith, Choosing Effective Laboratory Tests (Saunders, Philadelphia, Pa., 1983), pp. 357–365.

Spanner, G.

G. Spanner, R. Niessner, “New concept for the non-invasive determination of physiological glucose concentration using modulated laser diodes,” Fresenius J. Anal. Chem. 354, 306–310 (1996).

G. Spanner, R. Niessner, “Noninvasive determination of blood constituents using an array of modulated laser diodes and a photoacoustic sensor head,” Fresenius J. Anal. Chem. 355, 327–328 (1996).

Speicher, C. E.

C. E. Speicher, J. W. Smith, Choosing Effective Laboratory Tests (Saunders, Philadelphia, Pa., 1983), pp. 357–365.

Stallard, B. R.

M. R. Robinson, R. P. Eaton, D. M. Haaland, G. W. Koepp, E. V. Thomas, B. R. Stallard, P. L. Robinson, “Noninvasive glucose monitoring in diabetic patients: a preliminary evaluation,” Clin. Chem. 38, 1618–1622 (1992).
[PubMed]

Steffes, P. G.

R. V. Tarr, P. G. Steffes, “The noninvasive measure of d-glucose in the ocular aqueous humor using stimulated Raman spectroscopy,” IEEE/LEOS Newslett. 12(2), 22–27 (1998).

R. V. Tarr, P. G. Steffes, “Non-invasive blood glucose measurement system and method using stimulated Raman spectroscopy,” U.S. patent5,243,983 (14September1993).

Stith, R. D.

Suria, D.

J. J. Qu, O. L. Yau, S. M. Yau, D. Suria, B. C. Wilson, “Measurements of therapeutic drugs and substances of abuse in human body fluids by near-IR laser Raman spectroscopy with new algorithms,” in Biomedical Diagnostic, Guidance, and Surgical-Assist Systems, D. A. Benaron, R. D. Bucholz, S. T. Charles, W. S. Grundfest, M. W. Vannier, T. Vo-Dinh, eds., Proc. SPIE3595, (to be published).

Tarr, R. V.

R. V. Tarr, P. G. Steffes, “The noninvasive measure of d-glucose in the ocular aqueous humor using stimulated Raman spectroscopy,” IEEE/LEOS Newslett. 12(2), 22–27 (1998).

R. V. Tarr, P. G. Steffes, “Non-invasive blood glucose measurement system and method using stimulated Raman spectroscopy,” U.S. patent5,243,983 (14September1993).

Thomas, E. V.

D. M. Haaland, M. R. Robinson, G. W. Koepp, E. V. Thomas, R. P. Eaton, “Reagentless near-infrared determination of glucose in whole blood using multivariate calibration,” Appl. Spectrosc. 46, 1575–1578 (1992).
[CrossRef]

M. R. Robinson, R. P. Eaton, D. M. Haaland, G. W. Koepp, E. V. Thomas, B. R. Stallard, P. L. Robinson, “Noninvasive glucose monitoring in diabetic patients: a preliminary evaluation,” Clin. Chem. 38, 1618–1622 (1992).
[PubMed]

D. M. Haaland, E. V. Thomas, “Partial least-squares methods for spectral analyses. 1. Relation to other quantitative calibration methods and the extraction of qualitative information,” Anal. Chem. 60, 1193–1202 (1988).
[CrossRef]

Uenoyama, H.

Volka, K.

Walker, S. A.

Wang, S. Y.

Wang, Y.

Ward, K. J.

Watson, P. A.

Wicksted, J. P.

Wilson, B. C.

J. J. Qu, O. L. Yau, S. M. Yau, D. Suria, B. C. Wilson, “Measurements of therapeutic drugs and substances of abuse in human body fluids by near-IR laser Raman spectroscopy with new algorithms,” in Biomedical Diagnostic, Guidance, and Surgical-Assist Systems, D. A. Benaron, R. D. Bucholz, S. T. Charles, W. S. Grundfest, M. W. Vannier, T. Vo-Dinh, eds., Proc. SPIE3595, (to be published).

Yamaguchi, Y.

X. Dou, Y. Yamaguchi, H. Yamamoto, S. Doi, Y. Ozaki, “A highly sensitive, compact Raman system without a spectrometer for quantitative analysis of biological samples,” Vib. Spectrosc. 14, 199–205 (1997).
[CrossRef]

X. Dou, Y. Yamaguchi, H. Yamamoto, S. Doi, Y. Ozaki, “Quantitative analysis of metabolites in urine using a highly precise, compact near-infrared Raman spectrometer,” Vib. Spectrosc. 13, 83–89 (1996).
[CrossRef]

X. Dou, Y. Yamaguchi, H. Yamamoto, H. Uenoyama, Y. Ozaki, “Biological applications of anti-Stokes Raman spectroscopy: quantitative analysis of glucose in plasma and serum by a highly sensitive multichannel Raman spectrometer,” Appl. Spectrosc. 50, 1301–1306 (1996).
[CrossRef]

Yamamoto, H.

X. Dou, Y. Yamaguchi, H. Yamamoto, S. Doi, Y. Ozaki, “A highly sensitive, compact Raman system without a spectrometer for quantitative analysis of biological samples,” Vib. Spectrosc. 14, 199–205 (1997).
[CrossRef]

X. Dou, Y. Yamaguchi, H. Yamamoto, S. Doi, Y. Ozaki, “Quantitative analysis of metabolites in urine using a highly precise, compact near-infrared Raman spectrometer,” Vib. Spectrosc. 13, 83–89 (1996).
[CrossRef]

X. Dou, Y. Yamaguchi, H. Yamamoto, H. Uenoyama, Y. Ozaki, “Biological applications of anti-Stokes Raman spectroscopy: quantitative analysis of glucose in plasma and serum by a highly sensitive multichannel Raman spectrometer,” Appl. Spectrosc. 50, 1301–1306 (1996).
[CrossRef]

Yau, O. L.

J. J. Qu, O. L. Yau, S. M. Yau, D. Suria, B. C. Wilson, “Measurements of therapeutic drugs and substances of abuse in human body fluids by near-IR laser Raman spectroscopy with new algorithms,” in Biomedical Diagnostic, Guidance, and Surgical-Assist Systems, D. A. Benaron, R. D. Bucholz, S. T. Charles, W. S. Grundfest, M. W. Vannier, T. Vo-Dinh, eds., Proc. SPIE3595, (to be published).

Yau, S. M.

J. J. Qu, O. L. Yau, S. M. Yau, D. Suria, B. C. Wilson, “Measurements of therapeutic drugs and substances of abuse in human body fluids by near-IR laser Raman spectroscopy with new algorithms,” in Biomedical Diagnostic, Guidance, and Surgical-Assist Systems, D. A. Benaron, R. D. Bucholz, S. T. Charles, W. S. Grundfest, M. W. Vannier, T. Vo-Dinh, eds., Proc. SPIE3595, (to be published).

Anal. Chem.

M. A. Arnold, G. W. Small, “Determination of physiological levels of glucose in an aqueous matrix with digitally filtered Fourier transform near-infrared spectra,” Anal. Chem. 62, 1457–1464 (1990).
[CrossRef] [PubMed]

E. Peuchant, C. Salles, R. Jensen, “Determination of serum cholesterol by near-infrared reflectance spectrometry,” Anal. Chem. 59, 1816–1819 (1987).
[CrossRef] [PubMed]

D. M. Haaland, E. V. Thomas, “Partial least-squares methods for spectral analyses. 1. Relation to other quantitative calibration methods and the extraction of qualitative information,” Anal. Chem. 60, 1193–1202 (1988).
[CrossRef]

A. J. Berger, T.-W. Koo, I. Itzkan, M. S. Feld, “An enhanced algorithm for linear multivariate calibration,” Anal. Chem. 70, 623–628 (1998).
[CrossRef] [PubMed]

Anal. Chim. Acta

P. Geladi, B. R. Kowalski, “Partial least-squares regression: a tutorial,” Anal. Chim. Acta 185, 1–17 (1986).
[CrossRef]

B. Bauer, T. Floyd, “Monitoring of glucose in biological fluids by Fourier-transform infrared spectrometry with a cylindrical internal reflectance cell,” Anal. Chim. Acta 197, 295–301 (1987).
[CrossRef]

Appl. Opt.

Appl. Spectrosc.

X. Dou, Y. Yamaguchi, H. Yamamoto, H. Uenoyama, Y. Ozaki, “Biological applications of anti-Stokes Raman spectroscopy: quantitative analysis of glucose in plasma and serum by a highly sensitive multichannel Raman spectrometer,” Appl. Spectrosc. 50, 1301–1306 (1996).
[CrossRef]

J. P. Wicksted, R. J. Erckens, M. Motamedi, W. F. March, “Raman spectroscopy studies of metabolic concentrations in aqueous solutions and aqueous humor specimens,” Appl. Spectrosc. 49, 987–993 (1995).
[CrossRef]

H. M. Heise, R. Marbach, T. Koschinsky, F. A. Gries, “Multicomponent assay for blood substrates in human plasma by mid-infrared spectroscopy and its evaluation for clinical analysis,” Appl. Spectrosc. 48, 85–95 (1994).
[CrossRef]

D. M. Haaland, M. R. Robinson, G. W. Koepp, E. V. Thomas, R. P. Eaton, “Reagentless near-infrared determination of glucose in whole blood using multivariate calibration,” Appl. Spectrosc. 46, 1575–1578 (1992).
[CrossRef]

K. J. Ward, D. M. Haaland, M. R. Robinson, R. P. Eaton, “Post-prandial blood glucose determination by quantitative mid-infrared spectroscopy,” Appl. Spectrosc. 46, 959–965 (1992).
[CrossRef]

R. Marbach, T. Koschinsky, F. A. Gries, H. M. Heise, “Noninvasive blood glucose assay by near-infrared diffuse reflectance spectroscopy of the human inner lip,” Appl. Spectrosc. 47, 875–881 (1993).
[CrossRef]

G. Budínová, J. Salva, K. Volka, “Application of molecular spectroscopy in the mid-infrared region to the determination of glucose and cholesterol in whole blood and in blood serum,” Appl. Spectrosc. 51, 631–635 (1997).
[CrossRef]

K. Faber, B. R. Kowalski, “Improved prediction error estimates for multivariate calibration by correcting for the measurement error in the reference values,” Appl. Spectrosc. 51, 660–665 (1997).
[CrossRef]

A. J. Berger, M. S. Feld, “Analytical method of calculating chemometric prediction error,” Appl. Spectrosc. 51, 725–732 (1997).
[CrossRef]

Clin. Chem.

J. W. Hall, A. Pollard, “Near-infrared spectrophotometry: a new dimension in clinical chemistry,” Clin. Chem. 38, 1623–1631 (1992).
[PubMed]

M. R. Robinson, R. P. Eaton, D. M. Haaland, G. W. Koepp, E. V. Thomas, B. R. Stallard, P. L. Robinson, “Noninvasive glucose monitoring in diabetic patients: a preliminary evaluation,” Clin. Chem. 38, 1618–1622 (1992).
[PubMed]

Diabetes Care

W. L. Clarke, D. Cox, L. A. Gonder-Frederick, W. Carter, S. L. Pohl, “Evaluating clinical accuracy of systems for self-monitoring of blood glucose,” Diabetes Care 10, 622–628 (1987).
[CrossRef] [PubMed]

Fresenius J. Anal. Chem.

G. Spanner, R. Niessner, “Noninvasive determination of blood constituents using an array of modulated laser diodes and a photoacoustic sensor head,” Fresenius J. Anal. Chem. 355, 327–328 (1996).

G. Spanner, R. Niessner, “New concept for the non-invasive determination of physiological glucose concentration using modulated laser diodes,” Fresenius J. Anal. Chem. 354, 306–310 (1996).

IEEE Trans. Biomed. Eng.

Y. Mendelson, A. C. Clermont, R. A. Peura, B.-C. Lin, “Blood glucose measurement by multiple attenuated total reflection and infrared absorption spectroscopy,” IEEE Trans. Biomed. Eng. 37, 458–465 (1990).
[CrossRef] [PubMed]

F. M. Ham, I. N. Kostanic, G. M. Cohen, B. R. Gooch, “Determination of glucose concentrations in an aqueous matrix from NIR spectra using optimal time-domain filtering and partial least-squares regression,” IEEE Trans. Biomed. Eng. 44, 475–484 (1997).
[CrossRef] [PubMed]

G. L. Coté, M. D. Fox, R. B. Northrop, “Noninvasive optical polarimetric glucose sensing using a true phase measurement technique,” IEEE Trans. Biomed. Eng. 39, 752–756 (1992).
[CrossRef] [PubMed]

B. D. Cameron, G. L. Coté, “Noninvasive glucose sensing utilizing a digital closed-loop polarimetric approach,” IEEE Trans. Biomed. Eng. 44, 1221–1227 (1997).
[CrossRef] [PubMed]

M. J. Goetz, G. L. Coté, R. Erckens, W. March, M. Motamedi, “Application of a multivariate technique to Raman spectra for quantification of body chemicals,” IEEE Trans. Biomed. Eng. 42, 728–731 (1995).
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IEEE/LEOS Newslett.

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Figures (10)

Fig. 1
Fig. 1

Experimental setup for acquisition of Raman spectra from blood samples: BPF, bandpass filter; P, prism; S, blood sample; L1–L4, lenses; NF, notch filter; FB, fiber bundle. See text for details.

Fig. 2
Fig. 2

Twenty spectra from each of the two data sets, demonstrating the typical spread in the data: (a) serum, (b) whole blood.

Fig. 3
Fig. 3

Same data as in Fig. 2 after linear baseline subtraction, which removes the gross fluctuations, creating better overlap and emphasizing Raman peaks: (a) serum, (b) whole blood.

Fig. 4
Fig. 4

PLS predictions of analyte concentrations in serum data: (a) glucose, (b) cholesterol, (c) triglyceride, (d) urea (BUN), (e) total protein, (f) albumin.

Fig. 5
Fig. 5

Clarke error grid plot of glucose concentration predictions in serum. The predictions are all in the A and B regions, which are the desirable regions for clinical accuracy. See text for details.

Fig. 6
Fig. 6

PLS leave-half-out predictions of analyte concentrations in serum. The accuracy of the predictions implies that system drift effects are minor; see also Table 3 and the discussion in text. (a) Glucose, (b) cholesterol, (c) albumin.

Fig. 7
Fig. 7

Comparison of pure glucose Raman spectrum in saline (top), second PLS weight vector for glucose in serum (middle), and PLS b-vector for glucose prediction in serum (bottom). The appearance of glucose features in the weight vector and the b-vector demonstrate that the multivariate analysis has extracted the Raman signature of glucose.

Fig. 8
Fig. 8

PLS predictions of serum analyte concentrations from whole blood data. Although the plots are all less accurate than the results achieved for serum, four of the plots have visible correlations with r 2 values greater than 0.5. (a) Glucose, (b) cholesterol, (c) triglyceride, (d) urea (BUN), (e) total protein, (f) albumin.

Fig. 9
Fig. 9

Hematocrit cross-validation results for whole blood samples. The RMSEP is 2.7 percentage units, with an r 2 of 0.73. Reference analyzer accuracy is 0.4 percentage unit.

Fig. 10
Fig. 10

Spectra of glucose obtained in saline (PBS), serum, and whole blood. The signal from blood is seen to be approximately four times lower than that from the nonturbid media.

Tables (5)

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Table 1 PLS Prediction Results for Serum Data Set

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Table 2 Comparison of Healthy Adult Ranges of Serum Analyte Concentrationsa and RMSEP Values from PLS Concentration Predictionsb

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Table 3 Comparison of RMSEP Values for Odd–Even and Half-and-Half (i.e., Leave-Half-Out) Cross Validationsa

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Table 4 Correlation Coefficient Between Different Analytes’ Concentrations in the Serum Analysis Studya

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Table 5 PLS Prediction Results for Whole Blood Data Set

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