Laser secondary neutral mass spectrometry for copper detection in micro-scale biopsies

TY - JOUR

T1 - Laser secondary neutral mass spectrometry for copper detection in micro-scale biopsies

AU - Kriegeskotte, C

AU - Cantz, T

AU - Haberland, J

AU - Zibert, A

AU - Haier, J

AU - Köhler, G

AU - Schöler, H R

AU - Schmidt, H H-J

AU - Arlinghaus, H F

N1 - Copyright 2009 John Wiley & Sons, Ltd.

PY - 2009/10

Y1 - 2009/10

N2 - Disease progression and clinical diagnostics of a number of hereditable metabolic diseases are determined by organ involvement in disturbed deposition of certain molecules. Current clinical imaging is unable to visualize this maldistribution with sufficient specificity and sensitivity, such as in Wilson's disease. The quest for understanding cellular Cu distribution in these patients requires element- and molecule-specific images with nanometer-scale spatial resolution. We have used a new cryo-mass spectrometric instrument with an integrated cryosectioning chamber for preparation and analysis of frozen hydrated samples of Wilson's disease tissue. With laser post-ionization secondary neutral mass spectrometry (laser-SNMS), we were able to image Cu and other intrinsic elements and molecules in less than 1 mg of frozen hydrated liver tissue from a murine model of Wilson's disease. A 40-50 times higher Cu concentration was measured in the disease tissue as compared to the control mouse. Furthermore, major histomorphological changes were observed using this advanced nano-science tool. The results showed that the combination of in-vacuum cryosectioning and cryo-laser-SNMS technologies is particularly well suited for identifying specific cell structures and imaging trace element concentrations with subcellular resolution and upper-parts-per-billion sensitivity in biological samples. This technology can provide a novel diagnostic tool for clinical applications in various diseases involving trace elements.

AB - Disease progression and clinical diagnostics of a number of hereditable metabolic diseases are determined by organ involvement in disturbed deposition of certain molecules. Current clinical imaging is unable to visualize this maldistribution with sufficient specificity and sensitivity, such as in Wilson's disease. The quest for understanding cellular Cu distribution in these patients requires element- and molecule-specific images with nanometer-scale spatial resolution. We have used a new cryo-mass spectrometric instrument with an integrated cryosectioning chamber for preparation and analysis of frozen hydrated samples of Wilson's disease tissue. With laser post-ionization secondary neutral mass spectrometry (laser-SNMS), we were able to image Cu and other intrinsic elements and molecules in less than 1 mg of frozen hydrated liver tissue from a murine model of Wilson's disease. A 40-50 times higher Cu concentration was measured in the disease tissue as compared to the control mouse. Furthermore, major histomorphological changes were observed using this advanced nano-science tool. The results showed that the combination of in-vacuum cryosectioning and cryo-laser-SNMS technologies is particularly well suited for identifying specific cell structures and imaging trace element concentrations with subcellular resolution and upper-parts-per-billion sensitivity in biological samples. This technology can provide a novel diagnostic tool for clinical applications in various diseases involving trace elements.

KW - Animals

KW - Biopsy

KW - Copper

KW - Disease Models, Animal

KW - Frozen Sections

KW - Hepatolenticular Degeneration

KW - Lasers

KW - Liver

KW - Mass Spectrometry

KW - Mice

KW - Microchemistry

KW - Nanotechnology

U2 - 10.1002/jms.1634

DO - 10.1002/jms.1634

M3 - SCORING: Journal article

C2 - 19753579

VL - 44

SP - 1417

EP - 1422

JO - EUR J MASS SPECTROM

JF - EUR J MASS SPECTROM

SN - 1469-0667

IS - 10

ER -