Ultra-filtration of human serum for improved quantitative analysis of low molecular weight biomarkers using ATR-IR spectroscopy

Franck Bonnier, Hélène Blasco, Clément Wasselet, Guillaume Brachet, Renaud Respaud, Luis Felipe CS. Carvalho, Dominique Bertrand, Hugh J. Byrne, Matthew Baker, Igor Chourpa

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Infrared spectroscopy is a reliable, rapid and cost effective characterisation technique, delivering a molecular finger print of the sample. It is expected that its sensitivity would enable detection of small chemical variations in biological samples associated with disease. ATR-IR is particularly suitable for liquid sample analysis and, although air drying is commonly performed before data collection, just a drop of human serum is enough for screening and early diagnosis. However, the dynamic range of constituent biochemical concentrations in the serum composition remains a limiting factor to the reliability of the technique. Using glucose as a model spike in human serum, it has been demonstrated in the present study that fractionating the serum prior to spectroscopic analysis can considerably improve the precision and accuracy of quantitative models based on the Partial Least Squares Regression algorithm. By depleting the abundant high molecular weight proteins, which otherwise dominate the spectral signatures collected, the ability to monitor changes in the concentrations of the low molecular weight constituents is enhanced. The Root Mean Square Error for the Validation set (RMSEV) has been improved by a factor of 5 following human serum processing with an average relative error in the predictive values below 1% is achieved. Moreover, the approach is easily transferable to different bodily fluids, which would support the development of more efficient and suitable clinical protocols for exploration of vibrational spectroscopy based ex-vivo diagnostic tools.
LanguageEnglish
Pages1285-1298
Number of pages14
JournalAnalyst
Early online date22 Dec 2016
DOIs
Publication statusPublished - 21 Apr 2017

Fingerprint

Biomarkers
Ultrafiltration
ultrafiltration
quantitative analysis
biomarker
serum
Infrared spectroscopy
Spectrum Analysis
Molecular Weight
Molecular weight
spectroscopy
Vibrational spectroscopy
Spectroscopic analysis
Serum
Chemical analysis
Mean square error
Glucose
Drying
Screening
Proteins

Keywords

  • human serum fractionation
  • centrifugal filtration
  • infrared spectroscopy
  • attenuated tonal reflection
  • partial least squares regression
  • low molecular weight fraction
  • disease diagnosis

Cite this

Bonnier, F., Blasco, H., Wasselet, C., Brachet, G., Respaud, R., Carvalho, L. F. CS., ... Chourpa, I. (2017). Ultra-filtration of human serum for improved quantitative analysis of low molecular weight biomarkers using ATR-IR spectroscopy. Analyst, 1285-1298. https://doi.org/10.1039/C6AN01888B
Bonnier, Franck ; Blasco, Hélène ; Wasselet, Clément ; Brachet, Guillaume ; Respaud, Renaud ; Carvalho, Luis Felipe CS. ; Bertrand, Dominique ; Byrne, Hugh J. ; Baker, Matthew ; Chourpa, Igor. / Ultra-filtration of human serum for improved quantitative analysis of low molecular weight biomarkers using ATR-IR spectroscopy. In: Analyst. 2017 ; pp. 1285-1298.
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Bonnier, F, Blasco, H, Wasselet, C, Brachet, G, Respaud, R, Carvalho, LFCS, Bertrand, D, Byrne, HJ, Baker, M & Chourpa, I 2017, 'Ultra-filtration of human serum for improved quantitative analysis of low molecular weight biomarkers using ATR-IR spectroscopy' Analyst, pp. 1285-1298. https://doi.org/10.1039/C6AN01888B

Ultra-filtration of human serum for improved quantitative analysis of low molecular weight biomarkers using ATR-IR spectroscopy. / Bonnier, Franck; Blasco, Hélène; Wasselet, Clément; Brachet, Guillaume; Respaud, Renaud; Carvalho, Luis Felipe CS.; Bertrand, Dominique; Byrne, Hugh J.; Baker, Matthew; Chourpa, Igor.

In: Analyst, 21.04.2017, p. 1285-1298.

Research output: Contribution to journalArticle

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AU - Bonnier, Franck

AU - Blasco, Hélène

AU - Wasselet, Clément

AU - Brachet, Guillaume

AU - Respaud, Renaud

AU - Carvalho, Luis Felipe CS.

AU - Bertrand, Dominique

AU - Byrne, Hugh J.

AU - Baker, Matthew

AU - Chourpa, Igor

PY - 2017/4/21

Y1 - 2017/4/21

N2 - Infrared spectroscopy is a reliable, rapid and cost effective characterisation technique, delivering a molecular finger print of the sample. It is expected that its sensitivity would enable detection of small chemical variations in biological samples associated with disease. ATR-IR is particularly suitable for liquid sample analysis and, although air drying is commonly performed before data collection, just a drop of human serum is enough for screening and early diagnosis. However, the dynamic range of constituent biochemical concentrations in the serum composition remains a limiting factor to the reliability of the technique. Using glucose as a model spike in human serum, it has been demonstrated in the present study that fractionating the serum prior to spectroscopic analysis can considerably improve the precision and accuracy of quantitative models based on the Partial Least Squares Regression algorithm. By depleting the abundant high molecular weight proteins, which otherwise dominate the spectral signatures collected, the ability to monitor changes in the concentrations of the low molecular weight constituents is enhanced. The Root Mean Square Error for the Validation set (RMSEV) has been improved by a factor of 5 following human serum processing with an average relative error in the predictive values below 1% is achieved. Moreover, the approach is easily transferable to different bodily fluids, which would support the development of more efficient and suitable clinical protocols for exploration of vibrational spectroscopy based ex-vivo diagnostic tools.

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KW - disease diagnosis

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