Rotterdam, Netherlands
Rotterdam, Netherlands

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P. Santos I.,Erasmus Medical Center | van der Lee A.,The Innovation Group | Gu X.,Philips | Caspers P.J.,Erasmus Medical Center | And 5 more authors.
Journal of Raman Spectroscopy | Year: 2017

Raman spectroscopy of pigmented samples can be problematic owing to strong laser-induced auto-fluorescence. Moving the laser excitation more into the near-infrared region (>900 nm) and detection to the short-wave infrared region (SWIR) (1200-1600 nm) significantly decreases laser-induced-fluorescence for many pigmented samples. However, conventional near-infrared diode-lasers suitable for Raman spectroscopy are expensive. Vertical-external-cavity surface-emitting lasers (VECSELs) are an interesting alternative laser source for Raman spectroscopy. VECSELs offer a narrow linewidth, high power stability, good power efficiency and circular beam profile characteristics, and their wavelength can be engineered over a broad range in the near-infrared. In addition, they offer the potential of low-cost mass production, and they are small in size. We developed a 986-nm VECSEL for a specific biomedical application (Raman measurements of pigmented skin lesions). We implemented and tested the feasibility of the novel 986-nm VECSEL in a SWIR multi-channel Raman spectroscopy instrument. We have characterized the VECSEL in relation to the requirements set by this biomedical application and have demonstrated for the first time Raman spectra of pigmented skin lesion with a VECSEL in the SWIR region. Our results show that the VECSEL fulfils the requirements of a laser source to be applied in Raman spectroscopy. This opens the possibility of using VECSELs for low-cost compact hand-held Raman spectroscopy applications. © 2017 John Wiley & Sons, Ltd.


Pot L.M.,University of Groningen | Coenraads P.-J.,University of Groningen | Blomeke B.,University of Trier | Puppels G.J.,Erasmus University Rotterdam | And 3 more authors.
Contact Dermatitis | Year: 2016

Background Penetration, autoxidation and N-acetylation of p-phenylenediamine (PPD) have been studied in vitro and ex vivo. However, a clear understanding of in vivo PPD penetration and the formation of PPD derivatives is lacking. Objectives To obtain insights into the in vivo penetration, clearance and formation of PPD derivatives in human skin. Methods Patch test chambers containing PPD 1% pet. were applied to the forearms of two human volunteers, with increasing application times. Non-invasive Raman microspectroscopy was used for detection of PPD (derivatives) in skin at several follow-up times. Results Application of a PPD 1% pet. patch for 30 min resulted in substantial amounts of PPD in the stratum corneum of 90 mg PPD/g keratin. PPD contents were highest after three applications for 1 h each (330 mg PPD/g keratin), followed by single applications for 2 h 40 min, 2 h, and 23 h. The PPD half-time in the skin was 3 h. No spectral contributions of Bandrowski's base, monoacetyl-PPD and diacetyl-PPD were detected. Conclusions We have gained insights into the in vivo penetration of PPD in human skin by using non-invasive Raman spectroscopy. Penetration into the skin was fast, and the PPD concentrations detected in the stratum corneum were high. PPD was detected in both the stratum corneum and the viable epidermis. Oxidized or acetylated PPD derivatives could not be detected. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.


Byrne H.J.,Dublin Institute of Technology | Baranska M.,Jagiellonian University | Puppels G.J.,RiverD International | Puppels G.J.,Erasmus Medical Center | And 7 more authors.
Analyst | Year: 2015

Although the potential of vibrational spectroscopy for biomedical applications has been well demonstrated, translation into clinical practice has been relatively slow. This Editorial assesses the challenges facing the field and the potential way forward. While many technological challenges have been addressed to date, considerable effort is still required to gain acceptance of the techniques among the medical community, standardise protocols, extend to a clinically relevant scale, and ultimately assess the health economics underlying clinical deployment. National and international research networks can contribute much to technology development and standardisation. Ultimately, large-scale funding is required to engage in clinical trials and instrument development. © The Royal Society of Chemistry 2015.


Baclig A.C.,Erasmus University Rotterdam | Bakker Schut T.C.,Erasmus University Rotterdam | Bakker Schut T.C.,RiverD International | O'Regan G.M.,Our Ladys Childrens Hospital | And 7 more authors.
Journal of Raman Spectroscopy | Year: 2013

Loss-of-function mutations in the gene coding for filaggrin are the single most important risk factor for development of atopic dermatitis and associated allergic rhinitis and asthma. Filaggrin is enzymatically degraded to natural moisturizing factor (NMF) in the stratum corneum (SC). In vivo Raman spectra of human skin can be used to quantify the NMF concentration in SC and thereby identify carriers of a loss-of-function mutation in the gene coding for filaggrin, which results in decreased NMF content. Here, we demonstrate that strongly reduced Raman spectral information is sufficient to make this differentiation. This is an important step towards development of a dedicated diagnostic device of reduced complexity, size and cost as compared to current state-of-the-art Raman equipment. A genetic algorithm was used to select the spectral regions needed to classify skin based on normal or reduced NMF content in SC. Using the NMF content based on full spectral information as gold standard, only four Raman regions were required to create a linear discriminant analysis model that can differentiate between skin with low NMF and skin with normal NMF with a prediction accuracy of 93 %. Copyright © 2013 John Wiley & Sons, Ltd.


Santos I.P.,Rotterdam University | Caspers P.J.,Rotterdam University | Bakker Schut T.,Rotterdam University | Van Doorn R.,Leiden University | And 3 more authors.
Journal of Raman Spectroscopy | Year: 2015

Pigmented tissues are inaccessible to Raman spectroscopy using visible laser light because of the high level of laser-induced tissue fluorescence. The fluorescence contribution to the acquired Raman signal can be reduced by using an excitation wavelength in the near infrared range around 1000 nm. This will shift the Raman spectrum above 1100 nm, which is the principal upper detection limit for silicon-based CCD detectors. For wavelengths above 1100 nm indium gallium arsenide detectors can be used. However, InGaAs detectors have not yet demonstrated satisfactory noise level characteristics for demanding Raman applications. We have tested and implemented for the first time a novel sensitive InGaAs imaging camera with extremely low readout noise for multichannel Raman spectroscopy in the short-wave infrared (SWIR) region. The effective readout noise of two electrons is comparable to that of high quality CCDs and two orders of magnitude lower than that of other commercially available InGaAs detector arrays. With an in-house built Raman system we demonstrate detection of shot-noise limited high quality Raman spectra of pigmented samples in the high wavenumber region, whereas a more traditional excitation laser wavelength (671 nm) could not generate a useful Raman signal because of high fluorescence. Our Raman instrument makes it possible to substantially decrease fluorescence background and to obtain high quality Raman spectra from pigmented biological samples in integration times well below 20 s. Copyright © 2015 John Wiley & Sons, Ltd.


Janssens M.,Leiden University | Van Smeden J.,Leiden University | Puppels G.J.,Erasmus University Rotterdam | Puppels G.J.,RiverD International | And 4 more authors.
British Journal of Dermatology | Year: 2014

Background The barrier function of the skin is primarily provided by the stratum corneum (SC), the outermost layer of the skin. Skin barrier impairment is thought to be a primary factor in the pathogenesis of atopic eczema (AE). Filaggrin is an epidermal barrier protein and common mutations in the filaggrin gene strongly predispose for AE. However, the role of filaggrin mutations in the decreased skin barrier in AE is not fully understood. It was recently shown that changes in SC lipid composition and organization play a role in the reduced skin barrier in AE. Objectives To determine whether the lipid/protein ratio and the total dry SC mass per surface area are related to the skin barrier function of controls and patients with AE. Methods A case-control study was performed to compare nonlesional and lesional skin of AE with skin of controls. The dry SC mass was determined by tape-stripping and Squamescan™. The ratio between lipid and protein bands in the Raman spectrum was used to determine the lipid/protein ratio. Skin barrier function was assessed by transepidermal water loss. Results The results show that the dry SC mass per skin area is altered only in lesional SC of patients with AE compared with control subjects. The observed reduction in the lipid/protein ratio in SC of patients with AE was more pronounced, both in lesional and nonlesional SC and correlated strongly with the skin barrier function and disease severity. Conclusions The lipid/protein ratio plays a role in the reduced skin barrier function in AE. What's already known about this topic? Filaggrin mutations are a predisposing factor for atopic eczema (AE). In nonlesional and lesional stratum corneum (SC) of patients with AE the intercellular lipid composition and organization are altered. Changes in the SC lipid properties correlate with a reduced skin barrier function, but are not associated with filaggrin mutations. What does this study add? The dry SC mass, being a measure for SC thickness, is only lower in lesional AE SC compared with SC from controls. The lipid/protein ratio in SC is reduced in both nonlesional and lesional SC of patients with AE and strongly correlates with the impaired skin barrier function and disease severity of patients with AE. The lipid/protein ratio plays a more important role in the impaired skin barrier of AE than the SC thickness. © 2014 British Association of Dermatologists.


Santos I.P.,Erasmus Medical Center | Caspers P.J.,Erasmus Medical Center | Bakker Schut T.,Erasmus Medical Center | van Doorn R.,Leiden University | And 2 more authors.
Journal of Raman Spectroscopy | Year: 2015

Pigmented tissues are inaccessible to Raman spectroscopy using visible laser light because of the high level of laser-induced tissue fluorescence. The fluorescence contribution to the acquired Raman signal can be reduced by using an excitation wavelength in the near infrared range around 1000nm. This will shift the Raman spectrum above 1100nm, which is the principal upper detection limit for silicon-based CCD detectors. For wavelengths above 1100nm indium gallium arsenide detectors can be used. However, InGaAs detectors have not yet demonstrated satisfactory noise level characteristics for demanding Raman applications. We have tested and implemented for the first time a novel sensitive InGaAs imaging camera with extremely low readout noise for multichannel Raman spectroscopy in the short-wave infrared (SWIR) region. The effective readout noise of two electrons is comparable to that of high quality CCDs and two orders of magnitude lower than that of other commercially available InGaAs detector arrays. With an in-house built Raman system we demonstrate detection of shot-noise limited high quality Raman spectra of pigmented samples in the high wavenumber region, whereas a more traditional excitation laser wavelength (671nm) could not generate a useful Raman signal because of high fluorescence. Our Raman instrument makes it possible to substantially decrease fluorescence background and to obtain high quality Raman spectra from pigmented biological samples in integration times well below 20s. © 2015 John Wiley & Sons, Ltd.


Santos I.P.,Rotterdam University | Caspers P.J.,Rotterdam University | Bakker Schut T.C.,Rotterdam University | Van Doorn R.,Leiden University | And 4 more authors.
Analytical Chemistry | Year: 2016

Melanoma is a pigmented type of skin cancer, which has the highest mortality of all skin cancers. Because of the low clinical diagnostic accuracy for melanoma, an objective tool is needed to assist clinical assessment of skin lesions that are suspected of (early) melanoma. The aim of this study was to identify spectral differences in the CH region of HWVN (high-wavenumber) Raman spectra between melanoma and benign melanocytic lesions clinically suspected of melanoma. We used these spectral differences to explore preliminary classification models to distinguish melanoma from benign melanocytic lesions. Data from 82 freshly excised melanocytic lesions clinically suspected of melanoma were measured using an in-house built Raman spectrometer, which has been optimized for measurements on pigmented skin lesions (excitation wavelength 976 nm and a wavelength range of the Raman signal 1340-1540 nm). Clear spectral differences were observed between melanoma and benign melanocytic lesions. These differences can be assigned mainly to the symmetric CH2 stretching vibrations of lipids. Our results show that the Raman bands between 2840 and 2930 cm-1 have increased intensity for melanoma when compared to benign melanocytic lesions, suggesting an increase in lipid content in melanoma. These results demonstrate that spectroscopic information in the CH-stretching region of HWVN Raman spectra can discriminate melanoma from benign melanocytic lesions that are often clinically misdiagnosed as melanoma and that Raman spectroscopy has the potential to provide an objective clinical tool to improve the clinical diagnostic accuracy of skin lesions suspected of melanoma. © 2016 American Chemical Society.


van Smeden J.,Leiden University | Janssens M.,Leiden University | Kaye E.C.J.,Leiden University | Caspers P.J.,Erasmus University Rotterdam | And 4 more authors.
Experimental Dermatology | Year: 2014

An important feature of atopic eczema (AE) is a decreased skin barrier function. The stratum corneum (SC) lipids - comprised of ceramides (CERs), free fatty acids (FFAs) and cholesterol - fulfil a predominant role in the skin barrier function. In this clinical study, the carbon chain length distribution of SC lipids (FFAs and CERs) and their importance for the lipid organization and skin barrier function were examined in AE patients and compared with control subjects. A reduction in FFA chain length and an increase in unsaturated FFAs are observed in non-lesional and lesional SC of AE patients. The reduction in FFA chain length associates with a reduced CER chain length, suggesting a common synthetic pathway. The lipid chain length reduction correlates with a less dense lipid organization and a decreased skin barrier function. All changes are more pronounced in lesional SC compared with non-lesional skin. No association was observed between lipid properties and filaggrin mutations, an important predisposing factor for developing AE. The results of this study demonstrate an altered SC lipid composition and signify the importance of these changes (specifically regarding the CER and FFA chain lengths) for the impaired skin barrier function in AE. This provides insights into epidermal lipid metabolism as well as new opportunities for skin barrier repair. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.


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