Gerwin J Puppels

• PhD
• Managing Director at RiverD International B.V.

We present a hybrid Raman spectroscopy (RS) and partial wave spectroscopy (PWS) microscope for the characterization of molecular and structural tissue alterations. The PWS performance was assessed with surface roughness standards, while the Raman performance with a silicon crystal standard. We also validated the system on stomach and intestinal mou...

We have developed a method to determine the limit of detection (LoD) for quantitative measurement of exogenous analytes in the outer layer of the human skin by in vivo confocal Raman spectroscopy. The method is in accordance with the guidelines of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Us...

As for many solid cancers, laryngeal cancer is treated surgically, and adequate resection margins are critical for survival. Raman spectroscopy has the capacity to accurately differentiate between cancer and non-cancerous tissue based on their molecular composition, which has been proven in previous work. The aim of this study is to investigate whe...

Patients with oral cavity cancer are almost always treated with surgery. The goal is to remove the tumor with a margin of more than 5 mm of surrounding healthy tissue. Unfortunately, this is only achieved in about 15% to 26% of cases. Intraoperative assessment of tumor resection margins (IOARM) can dramatically improve surgical results. However, cu...

Near-infrared (NIR) fluorescence imaging using exogenous fluorescent agents provides whole-field images in real-time to assist the surgeon in the excision of a tumor. Although the method has high sensitivity, the specificity can sometimes be lower than expected. Raman spectroscopy can detect tumors with high specificity. Therefore, a combination of...

The study of human skin represents an important area of research and development in dermatology, toxicology, pharmacology and cosmetology, in order to assess the effects of exogenous agents, their interaction, their absorption mechanism, and/or their toxicity towards the different cutaneous structures. The processes can be parameterised by mathemat...

Background Protecting the skin barrier in early infancy may prevent atopic dermatitis (AD). We investigated if daily emollient use from birth to 2 months reduced AD incidence in high‐risk infants at 12 months. Methods This was a single‐center, two‐armed, investigator‐blinded, randomized controlled clinical trial (NCT03871998). Term infants identif...

A clear margin is an important prognostic factor for most solid tumours treated by surgery. Intraoperative fluorescence imaging using exogenous tumour-specific fluorescent agents has shown particular benefit in improving complete resection of tumour tissue. However, signal processing for fluorescence imaging is complex, and fluorescence signal inte...

The study of human skin represents an important area of research and development in dermatology, toxicology, pharmacology and cosmetology, in order to assess the effects of exogenous agents, their interaction, their absorption mechanism, and/or their toxicity towards the different cutaneous structures. The processes can be parameterised by mathemat...

Background Protecting the skin barrier in early infancy may prevent atopic dermatitis (AD). We investigated if daily emollient use from birth to 2 months reduced AD incidence in high risk infants at 12 months. Methods This was a single-center, two-armed, investigator-blinded, randomized controlled clinical trial (NCT03871998). Term infants identifi...

Oral potentially malignant disorders (OPMD) may precede oral squamous cell carcinoma (OSCC). Reported rates of malignant transformation of OPMD range from 3 to 50%. While some clinical, histological, and molecular factors have been associated with a high-risk OPMD, they are, to date, insufficiently accurate for treatment decision-making. Moreover,...

This study reports on the effects of insertion velocity, needle tip geometry and needle diameter on tissue deformation and maximum insertion force. Moreover, the effect of multiple insertions with the same needle on the maximum insertion force is reported. The tissue deformation and maximum insertion force strongly depend on the insertion velocity...

Atopic dermatitis (AD) is a common inflammatory skin disease among children with increasing prevalence in the past decades. The strongest and most widely replicated genetic risk factor for AD is a null mutation in the filaggrin gene (FLG) located on chromosome 1q21. FLG encodes the protein filaggrin, which is involved in the formation and homeostas...

Background Oral cavity squamous cell carcinoma (OCSCC) is the most frequent head and neck cancer. Surgery is the mainstay treatment for patients with OCSCC. In case of bone involvement, the affected bone needs to be resected. Cancer-free bone resection margins (BRMs) are of crucial importance: patients with cancer-free BRMs have a 2 times higher ch...

Background Differentiated oral intraepithelial dysplasia (DOIN) was described by Japanese pathologists in 2007 but is not recognized by the World Health Organization. As in the vulva and penis, differentiated dysplasia in the oral cavity is a diagnostic challenge. Objective We determined reliable histologic criteria for the diagnosis of DOIN and a...

Background In head and neck oncological surgery the goal is to achieve a complete tumor resection with acceptable remaining function and appearance. For oral cavity squamous cell carcinoma (OCSCC) only 15% of the resections are reported as adequate. Since 2013, we have performed intraoperative assessment of resection margins (IOARM) in our institut...

The goal of head and neck oncological surgery is complete tumor resection with adequate resection margins while preserving acceptable function and appearance. For oral cavity squamous cell carcinoma (OCSCC), different studies showed that only 15%-26% of all resections are adequate. A major reason for the low number of adequate resections is the lac...

For vulvar squamous cell carcinoma (VSCC), the mainstay of treatment is surgical removal with tumour-free margins. Surgeons still operate without objective tools that provide margin-status. This study assesses Raman spectroscopy potentiality for distinguishing ex-vivo VSCC from healthy tissue in 11 patients. Grid-based Raman maps were obtained from...

The composition of topical and transdermal formulations is known to determine the rate and the extent of drug delivery to and through the skin. However, to date, the role of excipients in these formulations on skin delivery of actives has received little attention from scientists in the field. Monitoring skin absorption of both drug and vehicle may...

Introduction Achieving adequate resection margins during oral cancer surgery is important to improve patient prognosis. Surgeons have the delicate task of achieving an adequate resection and safeguarding satisfactory remaining function and acceptable physical appearance, while relying on visual inspection, palpation, and preoperative imaging. Intra...

Fluorescence-guided surgery is an intraoperative optical imaging method that provides surgeons with real-time guidance for the delineation of tumours. Currently, in phase 1 and 2 clinical trials, evaluation of fluorescence-guided surgery is primarily focused on its diagnostic performance, although the corresponding outcome variables do not inform a...

Objective The depth of invasion (DOI) is considered an independent risk factor for occult lymph node metastasis in oral cavity squamous cell carcinoma (OCSCC). It is used to decide whether an elective neck dissection (END) is indicated in the case of a clinically negative neck for early stage carcinoma (pT1/pT2). However, there is no consensus on t...

We present the first clinical integration of a prototype device based on integrated auto-fluorescence imaging and Raman spectroscopy (Fast Raman device) for intra-operative assessment of surgical margins during Mohs micrographic surgery of basal cell carcinoma (BCC). Fresh skin specimens from 112 patients were used to optimise the tissue pre-proces...

Background Inadequate resection margins in oral cavity squamous cell carcinoma have an adverse effect on patient outcome. Intraoperative assessment provides immediate feedback enabling the surgeon to achieve adequate resection margins. The goal of this study was to evaluate the value of specimen-driven intraoperative assessment by comparing the mar...

Objectives Depth of invasion (DOI) is the most important predictor for lymph node metastasis (LNM) in early stage (T1-T2) oral cancer. The aim of this study is to validate the cut-off value of 4 mm on which the decision to perform an Elective Neck Dissection (END) is made. Materials and methods We performed a retrospective study in patients with p...

Previously, we reported the use of Confocal Raman Spectroscopy (CRS) to investigate the topical delivery of actives and excipients. We have also correlated the results from CRS with findings from in vitro diffusion studies in human skin. However, until now CRS has only been used as a semi-quantitative method of determining the skin uptake of molecu...

With an incidence of 350.000 new cases per year, cancer of the oral cavity ranks among the 10 most common solid organ cancers. Most of these cancers are squamous cell carcinomas. Five‐year survival is about 50%. It has been shown that clear resection margins (>5 mm healthy tissue surrounding the resected tumor) have a significant positive effect on...

Background: Carriers of loss-of-function mutations in the filaggrin (LoF FLG) gene have less natural moisturising factor (NMF) in their stratum corneum (SC) and an increased risk of atopic dermatitis (AD). NMF can be measured non-invasively by Raman spectroscopy. The use of Raman-derived NMF at birth to screen for FLG genotype could inform targete...

This paper describes a unique non‐invasive capability to determine the concentration (in mg/cm3) and total amount of topically applied materials in the skin (in μg/cm2 of skin surface). It is based on in vivo confocal Raman spectroscopy. A theoretical derivation is given of a general method to calculate a concentration ratio from a Raman spectrum o...

Background & Objective: Differentiated oral intraepithelial dysplasia (DOIN) was described by Japanese pathologists in 2007 but is not recognized by the WHO. As in the vulva and penis, differentiated dysplasia in the oral cavity is a diagnostic challenge. We determined reliable histological criteria for the diagnosis of DOIN and assessed the useful...

Background Specimen‐driven intraoperative assessment of the resection margins provides immediate feedback if an additional excision is needed. However, relocation of an inadequate margin in the wound bed has shown to be difficult. The objective of this study is to assess a reliable method for accurate relocation of inadequate tumor resection margin...

Background Clinical diagnosis of early melanoma (Breslow thickness less than 0.8 mm) is crucial to disease-free survival. However, it is subjective and can be exceedingly difficult, leading to missed melanomas, or unnecessary excision of benign pigmented skin lesions. An objective technique is needed to improve the diagnosis of early melanoma. Met...

A Raman tissue spectrum is a quantitative representation of the overall molecular composition of that tissue. Raman spectra are often used as tissue fingerprints without further interpretation of the specific information that they contain about the tissue’s molecular composition. In this study, we analyzed the differences in molecular composition b...

We demonstrate the feasibility of short wave infrared (SWIR) spectroscopy combined with tape stripping for depth profiling of lipids and water in the stratum corneum of human skin. The proposed spectroscopic technique relies on differential detection at three wavelengths of 1720, 1750, and 1770 nm, with varying ratio of the lipid-to-water absorptio...

Resection margins are frequently studied in patients with oral squamous cell carcinoma and are accepted as a constant prognostic factor. While most evidence is based on soft tissue margins, reported data for bone resection margins are scarce. The aim of this retrospective study was to evaluate and determine the utility of surgical margins in bone r...

Objectives: The aim of this study was to investigate the potential of Raman spectroscopy for detection of oral cavity squamous cell carcinoma (OCSCC) in bone resection surfaces during mandibulectomy. Materials & methods: Raman mapping experiments were performed on fresh mandible resection specimens from patients treated with mandibulectomy for O...

Raman spectroscopy in the high-wavenumber spectral region (HWR) is particularly suited for fiber-optic in-vivo medical applications. The most-used fiber-optic materials have negligible Raman signal in the HWR. This enables the use of simple and cheap single-fiber-optic probes that can be fitted in endoscopes and needles. The HWR generally shows les...

We present a fully-automated device combining auto-fluorescence imaging and Raman spectroscopy capable of investigating skin resection margins in 30 minutes. The table top-device can easily fit in a surgery theatre.

Multimodal spectral histopathology (MSH), an optical technique combining tissue auto-fluorescence (AF) imaging and Raman micro-spectroscopy (RMS), was previously proposed for detection of residual basal cell carcinoma (BCC) at the surface of surgically-resected skin tissue. Here we report the development of a fully-automated prototype instrument ba...

Oncological applications of Raman spectroscopy have been contemplated, pursued, and developed at academic level for at least 25 years. Published studies aim to detect pre-malignant lesions, detect cancer in less invasive stages, reduce the number of unnecessary biopsies and guide surgery towards the complete removal of the tumour with adequate tumo...

Background/aims: Sensitive skin (SS), a frequently reported condition in the Western world, has been suggested to be underlined by an impaired skin barrier. The aim of this study was to investigate the skin barrier molecular composition in SS subjects using confocal Raman microspectroscopy (CRS), and to compare it with that of non-SS (NSS) individ...

Raman spectroscopy is a non-invasive and label-free optical technique that provides detailed information about the molecular composition of a sample. In this study, we evaluated the potential of Raman spectroscopy to predict skin toxicity due to tyrosine-kinase inhibitors treatment. We acquired Raman spectra of skin of patients undergoing treatment...

Background: Natural moisturizing factors (NMF) is used as genotypic and phenotypic biomarker in diagnostics. This study is a side-to-side comparison of two different methods to determine NMF in atopic dermatitis patients: Raman microspectroscopy and stratum corneum tape stripping followed by HPLC. Results: Measured NMF values were significantly...

Background: Currently, up to 85% of the oral resection specimens have inadequate resection margins, of which the majority is located in the deeper soft tissue layers. The prognosis of patients with oral cavity squamous cell carcinoma (OCSCC) of the tongue is negatively affected by these inadequate surgical resections. Raman spectroscopy, an optica...

Adequate resection of oral cavity squamous cell carcinoma (OCSCC) means complete tumor removal with a clear margin of more than 5 mm. For OCSCC 85% of the surgical resections appear inadequate. Raman spectroscopy is an objective and fast tool that can provide real-time information about the molecular composition of tissue and has the potential to p...

Melanoma is a pigmented type of skin cancer, which has the highest mortality of all skin cancers. Due to 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 H...

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 ski...

The poor prognosis of oral cavity squamous cell carcinoma (OCSCC) patients is associated with residual tumor after surgery. Raman spectroscopy has the potential to provide an objective intra-operative evaluation of the surgical margins. Our aim was to understand the discriminatory basis of Raman spectroscopy at a histological level. In total, 127 p...

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, wh...

The aim of this review was to identify publications on resection margins in oral cancer surgery, and compare these with the results from two Dutch academic medical centers. Eight publications were considered relevant for this study, reporting 30 to 65 percent inadequate resection margins (i.e. positive- and close margins), compared to 85 percent in...

Tumor-positive resection margins are a major problem in oral cancer surgery. High-wavenumber Raman spectroscopy is a reliable technique to determine the water content of tissues which may contribute to differentiate between tumor and healthy tissue. The aim of this study was to examine the use of Raman spectroscopy to differentiate tumor from surro...

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 r...

An instrument, method, use and software program to obtain information rapidly about microorganisms that may spread uncontrolled in hospitals, water supply, food or when used in bio terrorism are described. Vibrational spectroscopy provides data to a computer linked to one or more databases. Comparison of the spectral data and information retrieved...

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 o...

An earlier and more accurate detection of (small) cancerous and precancerous lesions in the oral cavity is essential to improve the prognosis of oral squamous cell carcinomas. Raman spectroscopy is being pursued as a potential method to realize this improvement, since the technique provides objective information on a biochemical level and can be us...

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...

A spectroscopic apparatus for determining a concentration and/or spatial gradient of an analyte of a bodily fluid that provides determination of a position of a capillary vessel within a biological sample in order to focus spectroscopic excitation radiation to a volume that is in close proximity to the capillary vessel but does not overlap with the...

This paper describes a new in vivo Raman probe that allows investigation of areas of the body that are otherwise difficult to access. It is coupled to a previously described commercially available in vivo Raman spectrometer that samples the skin through an optical flat. In the work presented here, the laser light emerges from a smaller pen-shaped p...

An integrated arrayed-waveguide grating (AWG) fabricated in silicon oxynitride (SiON) technology is used as the wavelength separation and selection element for Raman spectroscopy. With a spectral resolution of 5.5 nm and a free spectral range of 215 nm, the AWG enables wavelength separation of the full Raman fingerprint region in a single diffracti...

Enterobacteriaceae are important pathogens of both nosocomial and community-acquired infections. In particular, strains with broad-spectrum beta-lactamases increasingly cause problems in health care settings. Rapid and reliable typing systems are key tools to identify transmission, so that targeted infection control measures can be taken. In this s...

Filaggrin (FLG) mutations result in reduced stratum corneum (SC) natural moisturizing factor (NMF) components and consequent increased SC pH. Because higher pH activates SC protease activity, we hypothesized an enhanced release of proinflammatory IL-1 cytokines from corneocytes in patients with atopic dermatitis (AD) with FLG mutations (AD(FLG)) co...

We designed an arrayed-waveguide grating spectrometer for the detection of early dental caries in teeth through polarized Raman spectroscopy. Measurement results on extracted human teeth demonstrate the feasibility of the approach.

An integrated arrayed-waveguide grating fabricated in silicon-oxynitride technology is applied to Raman spectroscopy. After its validation by reproducing the well-known spectrum of cyclohexane, polarized Raman spectra are measured of extracted human teeth containing localized initial carious lesions. Excellent agreement is obtained between the spec...

We measured Raman spectra of extracted human teeth using an integrated arrayed-waveguide-grating spectrometer fabricated in silicon-oxynitride technology. The results represent a step towards the realization of compact, hand-held, integrated spectrometers for the detection of early dental caries.

Caspase-14 is a protease that is mainly expressed in suprabasal epidermal layers and activated during keratinocyte cornification. Caspase-14-deficient mice display reduced epidermal barrier function and increased sensitivity to UVB radiation. In these mice, profilaggrin, a protein with a pivotal role in skin barrier function, is processed correctly...

Clin Microbiol Infect 2012; 18: 147–152 In order to perform a cost-effective search and destroy policy for methicillin-resistant Staphylococcus aureus (MRSA), a quick and reliable typing method is essential. In an area with a high level of animal-related MRSA ST398, pulsed field gel electrophoresis (PFGE) typing and spa-typing are not sufficient to...

We have designed an arrayed-waveguide grating in silicon oxynitride technology for the detection of Raman signals from tooth enamel in the spectral region between 890 nm and 912 nm. The detected signals for both parallel and cross polarizations are used to distinguish between healthy and carious regions on the tooth surface of extracted human teeth...

We have designed a polarization insensitive arrayed-waveguide grating as a wavelength-selective device for Raman spectroscopy of the skin. The integrated spectrometer was characterized. Experimental results are presented and compared with a simulation. We tested our device in a novel confocal arrangement with a similar device that was used for focu...

Filaggrin (FLG) has a central role in the pathogenesis of atopic dermatitis (AD). FLG is a complex repetitive gene; highly population-specific mutations and multiple rare mutations make routine genotyping complex. Furthermore, the mechanistic pathways through which mutations in FLG predispose to AD are unclear. We sought to determine whether specif...