Abstract

Although skin is easily accessible to optical methodologies, a portable measurement head is necessary to allow ready spectroscopic interrogation of all anatomic locations. However, most conventional Raman microspectrometers and even dermatologic-specific Raman systems are fixed systems ill-suited to anatomic accessibility. To this end, we have developed a portable Raman microspectrometer system for future dermatologic studies. An in-house-built bench-top system was used to qualify the optical components and design. Based on this system’s layout, a handheld microspectrometer was developed for future clinical application. This system produces similar operating characteristics to the bench-top prototype, and is shown to provide clear Raman spectra from skin tissue measured in vivo in clinically-feasible integration times.

© 2007 Optical Society of America

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2006 (1)

L. Chrit, P. Bastien, G. D. Sockalingum, D. Batisse, F. Leroy, M. Manfait, and C. Hadjur, "An in vivo randomized study of human skin moisturization by a new confocal Raman fiber-optic microprobe: assessment of a glycerol-based hydration cream," Skin pharmacology and physiology 19, 207-215 (2006).
[CrossRef] [PubMed]

2005 (1)

L. Chrit, C. Hadjur, S. Morel, G. Sockalingum, G. Lebourdon, F. Leroy, and M. Manfait, "In vivo chemical investigation of human skin using a confocal Raman fiber optic microprobe," J. Biomed. Opt. 10, 44007 (2005).
[CrossRef] [PubMed]

2003 (4)

P. J. Caspers, G. W. Lucassen, and G. J. Puppels, "Combined in vivo confocal Raman spectroscopy and confocal microscopy of human skin," Biophys. J. 85, 572-580 (2003).
[CrossRef] [PubMed]

L. D. Swindle, S. G. Thomas, M. Freeman, and P. M. Delaney, "View of normal human skin in vivo as observed using fluorescent fiber-optic confocal microscopic imaging," J. Invest. Dermatol. 121, 706-712 (2003).
[CrossRef] [PubMed]

J. P. Kelly, A. H. Weiss, Q. Zhou, S. Schmode, and A. W. Dreher, "Imaging a child's fundus without dilation using a handheld confocal scanning laser ophthalmoscope," Arch. Ophthalmol. (Chicago). 121, 391-396 (2003).

H. G. Edwards, E. M. Newton, D. L. Dickensheets, and D. D. Wynn-Williams, "Raman spectroscopic detection of biomolecular markers from Antarctic materials: evaluation for putative Martian habitats," Spectrochim. Acta A 59, 2277-2290 (2003).
[CrossRef]

2002 (2)

A. Nijssen, T. C. Bakker Schut, F. Heule, P. J. Caspers, D. P. Hayes, M. H. A. Neumann, and G. J. Puppels, "Discriminating basal cell carcinoma from its surrounding tissue by Raman spectroscopy," J. Invest. Dermatol. 119, 64-69 (2002).
[CrossRef] [PubMed]

N. Stone, C. Kendall, N. Shepherd, P. Crow, and H. Barr, "Near-infrared Raman spectroscopy for the classification of epithelial pre-cancers and cancers," J. Raman Spectrosc. 33, 564-573 (2002).
[CrossRef]

2001 (2)

P. J. Caspers, G. W. Lucassen, E. A. Carter, H. A. Bruining, and G. J. Puppels, "In vivo confocal Raman microspectroscopy of the skin: Noninvasive determination of molecular concentration profiles," J. Invest. Dermatol. 116, 434-442 (2001).
[CrossRef] [PubMed]

H. P. Buschman, G. Deinum, J. T. Motz, M. Fitzmaurice, J. R. Kramer, A. van der Laarse, A. V. Bruschke, and M. S. Feld, "Raman microspectroscopy of human coronary atherosclerosis: Biochemical assessment of cellular and extracellular morphologic structures in situ," Cardiovasc. Pathol. 10, 69-82 (2001).
[CrossRef] [PubMed]

2000 (4)

H. P. Buschman, E. T. Marple, M. L. Wach, B. Bennett, T. C. Schut, H. A. Bruining, A. V. Bruschke, A. van der Laarse, and G. J. Puppels, "In vivo determination of the molecular composition of artery wall by intravascular Raman spectroscopy," Anal. Chem. 72, 3771-3775 (2000).
[CrossRef] [PubMed]

E. B. Hanlon, R. Manoharan, T. W. Koo, K. E. Shafer, J. T. Motz, M. Fitzmaurice, J. R. Kramer, I. Itzkan, R. R. Dasari, and M. S. Feld, "Prospects for in vivo Raman spectroscopy," Phys. Med. Biol. 45, R1-59 (2000).
[CrossRef] [PubMed]

P. J. Caspers, G. W. Lucassen, H. A. Bruining, and G. J. Puppels, "Automated depth-scanning confocal Raman microspectrometer for rapid in vivo determination of water concentration profiles in human skin," J. Raman Spectrosc. 31, 813-818 (2000).
[CrossRef]

D. L. Dickensheets, D. D. Wynn-Williams, H. G. M. Edwards, C. Schoen, C. Crowder, and E. M. Newton, "A novel miniature confocal microscope/Raman spectrometer system for biomolecular analysis on future Mars missions after Antarctic trials," J. Raman Spectrosc. 31, 633-635 (2000).
[CrossRef]

1999 (1)

M. Rajadhyaksha, S. Gonzalez, J. M. Zavislan, R. R. Anderson, and R. H. Webb, "In vivo confocal scanning laser microscopy of human skin II: Advances in instrumentation and comparison with histology," J. Invest. Dermatol. 113, 293-303 (1999).
[CrossRef] [PubMed]

1998 (1)

1997 (1)

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

1996 (1)

A. Mahadevan-Jansen, and R. Richards-Kortum, "Raman spectroscopy for the detection of cancers and precancers," J. Biomed. Opt. 1, 31-70 (1996).
[CrossRef]

1995 (2)

M. Rajadhyaksha, M. Grossman, D. Esterowitz, R. H. Webb, and R. R. Anderson, "In vivo confocal scanning laser microscopy of human skin: melanin provides strong contrast," J. Invest. Dermatol. 104, 946-952 (1995).
[CrossRef] [PubMed]

Y. E. Gorbaty and G. V. Bondarenko, "High-pressure high-temperature Raman cell for corrosive liquids," Rev. Sci. Instrum. 66, 4347-4349 (1995).
[CrossRef]

1993 (1)

D. Schiferl, S. K. Sharma, T. F. Cooney, S. Y. Wang, and K. Mohanan, "Multichannel Raman spectrometry system for weakly scattering materials at simultaneous high pressures and high temperatures," Rev. Sci. Instrum. 64, 2821-2827 (1993).
[CrossRef]

1992 (1)

1987 (1)

Anal. Chem. (1)

H. P. Buschman, E. T. Marple, M. L. Wach, B. Bennett, T. C. Schut, H. A. Bruining, A. V. Bruschke, A. van der Laarse, and G. J. Puppels, "In vivo determination of the molecular composition of artery wall by intravascular Raman spectroscopy," Anal. Chem. 72, 3771-3775 (2000).
[CrossRef] [PubMed]

Appl. Spectrosc. (2)

Biophys. J. (1)

P. J. Caspers, G. W. Lucassen, and G. J. Puppels, "Combined in vivo confocal Raman spectroscopy and confocal microscopy of human skin," Biophys. J. 85, 572-580 (2003).
[CrossRef] [PubMed]

Cardiovasc. Pathol. (1)

H. P. Buschman, G. Deinum, J. T. Motz, M. Fitzmaurice, J. R. Kramer, A. van der Laarse, A. V. Bruschke, and M. S. Feld, "Raman microspectroscopy of human coronary atherosclerosis: Biochemical assessment of cellular and extracellular morphologic structures in situ," Cardiovasc. Pathol. 10, 69-82 (2001).
[CrossRef] [PubMed]

Chicago). (1)

J. P. Kelly, A. H. Weiss, Q. Zhou, S. Schmode, and A. W. Dreher, "Imaging a child's fundus without dilation using a handheld confocal scanning laser ophthalmoscope," Arch. Ophthalmol. (Chicago). 121, 391-396 (2003).

J. Biomed. Opt. (2)

L. Chrit, C. Hadjur, S. Morel, G. Sockalingum, G. Lebourdon, F. Leroy, and M. Manfait, "In vivo chemical investigation of human skin using a confocal Raman fiber optic microprobe," J. Biomed. Opt. 10, 44007 (2005).
[CrossRef] [PubMed]

A. Mahadevan-Jansen, and R. Richards-Kortum, "Raman spectroscopy for the detection of cancers and precancers," J. Biomed. Opt. 1, 31-70 (1996).
[CrossRef]

J. Invest. Dermatol. (5)

P. J. Caspers, G. W. Lucassen, E. A. Carter, H. A. Bruining, and G. J. Puppels, "In vivo confocal Raman microspectroscopy of the skin: Noninvasive determination of molecular concentration profiles," J. Invest. Dermatol. 116, 434-442 (2001).
[CrossRef] [PubMed]

A. Nijssen, T. C. Bakker Schut, F. Heule, P. J. Caspers, D. P. Hayes, M. H. A. Neumann, and G. J. Puppels, "Discriminating basal cell carcinoma from its surrounding tissue by Raman spectroscopy," J. Invest. Dermatol. 119, 64-69 (2002).
[CrossRef] [PubMed]

M. Rajadhyaksha, S. Gonzalez, J. M. Zavislan, R. R. Anderson, and R. H. Webb, "In vivo confocal scanning laser microscopy of human skin II: Advances in instrumentation and comparison with histology," J. Invest. Dermatol. 113, 293-303 (1999).
[CrossRef] [PubMed]

M. Rajadhyaksha, M. Grossman, D. Esterowitz, R. H. Webb, and R. R. Anderson, "In vivo confocal scanning laser microscopy of human skin: melanin provides strong contrast," J. Invest. Dermatol. 104, 946-952 (1995).
[CrossRef] [PubMed]

L. D. Swindle, S. G. Thomas, M. Freeman, and P. M. Delaney, "View of normal human skin in vivo as observed using fluorescent fiber-optic confocal microscopic imaging," J. Invest. Dermatol. 121, 706-712 (2003).
[CrossRef] [PubMed]

J. Raman Spectrosc. (4)

N. Stone, C. Kendall, N. Shepherd, P. Crow, and H. Barr, "Near-infrared Raman spectroscopy for the classification of epithelial pre-cancers and cancers," J. Raman Spectrosc. 33, 564-573 (2002).
[CrossRef]

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

P. J. Caspers, G. W. Lucassen, H. A. Bruining, and G. J. Puppels, "Automated depth-scanning confocal Raman microspectrometer for rapid in vivo determination of water concentration profiles in human skin," J. Raman Spectrosc. 31, 813-818 (2000).
[CrossRef]

D. L. Dickensheets, D. D. Wynn-Williams, H. G. M. Edwards, C. Schoen, C. Crowder, and E. M. Newton, "A novel miniature confocal microscope/Raman spectrometer system for biomolecular analysis on future Mars missions after Antarctic trials," J. Raman Spectrosc. 31, 633-635 (2000).
[CrossRef]

Opt. Lett. (1)

Phys. Med. Biol. (1)

E. B. Hanlon, R. Manoharan, T. W. Koo, K. E. Shafer, J. T. Motz, M. Fitzmaurice, J. R. Kramer, I. Itzkan, R. R. Dasari, and M. S. Feld, "Prospects for in vivo Raman spectroscopy," Phys. Med. Biol. 45, R1-59 (2000).
[CrossRef] [PubMed]

Rev. Sci. Instrum. (2)

Y. E. Gorbaty and G. V. Bondarenko, "High-pressure high-temperature Raman cell for corrosive liquids," Rev. Sci. Instrum. 66, 4347-4349 (1995).
[CrossRef]

D. Schiferl, S. K. Sharma, T. F. Cooney, S. Y. Wang, and K. Mohanan, "Multichannel Raman spectrometry system for weakly scattering materials at simultaneous high pressures and high temperatures," Rev. Sci. Instrum. 64, 2821-2827 (1993).
[CrossRef]

Skin pharmacology and physiology (1)

L. Chrit, P. Bastien, G. D. Sockalingum, D. Batisse, F. Leroy, M. Manfait, and C. Hadjur, "An in vivo randomized study of human skin moisturization by a new confocal Raman fiber-optic microprobe: assessment of a glycerol-based hydration cream," Skin pharmacology and physiology 19, 207-215 (2006).
[CrossRef] [PubMed]

Spectrochim. Acta A (1)

H. G. Edwards, E. M. Newton, D. L. Dickensheets, and D. D. Wynn-Williams, "Raman spectroscopic detection of biomolecular markers from Antarctic materials: evaluation for putative Martian habitats," Spectrochim. Acta A 59, 2277-2290 (2003).
[CrossRef]

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Figures (6)

Fig. 1.
Fig. 1.

Schematic of prototype bench-top confocal Raman microscope (CRM). ECDL=laser, AP=anamorphic prism pair, C+=positive cylindrical lens, BP=bandpass filter, DM=dichroic mirror, M=mirror, BS=50/50 beamsplitter, SP=shortpass filter, LP=longpass filter, Obj=microscope objective.

Fig. 2.
Fig. 2.

Noticeable effect of stabilizing window for in vivo Raman measurement of stratum corneum; 60 sec. integration.

Fig. 3.
Fig. 3.

Schematic of handheld CRM with components and approximate dimensions. C=collimator, M=mirror, BP=bandpass filter, DM=dichroic mirror, LP=longpass filter, CM=concave mirror.

Fig. 4.
Fig. 4.

(A) Mean intensity (normalized) of cellophane Raman peaks at 810, 971, 1167, 1328, and 1458 cm-1 versus axial position of the objective, Gaussian approximation used for estimation of axial resolution, and theoretical response. FWHM is shown to be ~14 µm. (B) Theoretical lateral response used to determine lateral resolution; FWHM is shown to be ~1.2 µm.

Fig. 5.
Fig. 5.

Raman spectra collected by the handheld CRM system: (A) acetaminophen, (B) cellophane film, and (C) human skin measured in vivo before and after noise processing.

Fig. 6.
Fig. 6.

Raman spectra of powdered tryptophan measured by the bench-top and handheld CRM systems developed in-house and with a commercially available CRM.

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