MacGyver y la tecnocreatividad

Artículo para la sección Tribuna de adComunic

Raman spectroscopy for skin cancer diagnosis and characterisation of thin supported lipid films

Raman spectroscopy is a powerful tool in oncological imaging. Optical biopsies in which an accurate diagnosis of the tumour areas is spectroscopically performed are especially interesting for application to skin cancer treatments. In the first part of this dissertation a study on automated Raman spectral imaging allowed accurate diagnosis and delineation of the borders of a common type of skin cancer, basal cell carcinoma (BCC). Automated detection and imaging of BCC in skin sections excised during surgery was performed by combining Raman micro-spectroscopy with supervised multivariate mathematical algorithms based on linear discriminant analysis (LDA). The model allowed 90±9% sensitivity and 85±9% specificity in BCC detection. Raman spectral images based on the LDA model were created and compared with the gold-standard of the conventional histopathological diagnoses resulting in excellent agreement. Additional studies on the ability of the model in discriminating between BCC and hair follicles produced accurate diagnoses. In this thesis instrumental implementation and design of a Raman spectral imaging prototype aiming to reduce the acquisition time required to build the Raman spectral images was developed. High sensitivity variants of Raman spectroscopy such as surface enhanced Raman spectroscopy (SERS) are known to enable optical detection down to single molecules and can be applied to thin supported lipid research. The combination of SERS with a complementary topographic technique simultaneously synchronised adds to the chemical information the morphology of the sample surface. In the second part of this thesis simultaneous atomic force microscopy (AFM) and SERS characterisation of thin (≈15-20 nm) supported films of arachidic acid and cationic phospholipids on sapphire/silver substrates was successfully achieved. Supports were fabricated with nanosphere lithographic procedures and allowed enhancement of the weak Raman signals from the amphiphilic films by a maximum factor of ×10^8

Raman spectroscopy for skin cancer diagnosis and characterisation of thin supported lipid films

Raman spectroscopy is a powerful tool in oncological imaging. Optical biopsies in which an accurate diagnosis of the tumour areas is spectroscopically performed are especially interesting for application to skin cancer treatments. In the first part of this dissertation a study on automated Raman spectral imaging allowed accurate diagnosis and delineation of the borders of a common type of skin cancer, basal cell carcinoma (BCC). Automated detection and imaging of BCC in skin sections excised during surgery was performed by combining Raman micro-spectroscopy with supervised multivariate mathematical algorithms based on linear discriminant analysis (LDA). The model allowed 90±9% sensitivity and 85±9% specificity in BCC detection. Raman spectral images based on the LDA model were created and compared with the gold-standard of the conventional histopathological diagnoses resulting in excellent agreement. Additional studies on the ability of the model in discriminating between BCC and hair follicles produced accurate diagnoses. In this thesis instrumental implementation and design of a Raman spectral imaging prototype aiming to reduce the acquisition time required to build the Raman spectral images was developed. High sensitivity variants of Raman spectroscopy such as surface enhanced Raman spectroscopy (SERS) are known to enable optical detection down to single molecules and can be applied to thin supported lipid research. The combination of SERS with a complementary topographic technique simultaneously synchronised adds to the chemical information the morphology of the sample surface. In the second part of this thesis simultaneous atomic force microscopy (AFM) and SERS characterisation of thin (≈15-20 nm) supported films of arachidic acid and cationic phospholipids on sapphire/silver substrates was successfully achieved. Supports were fabricated with nanosphere lithographic procedures and allowed enhancement of the weak Raman signals from the amphiphilic films by a maximum factor of ×10^8

A 2D computational parametric analysis of the sheltering effect of fences on a railway vehicle standing on a bridge and experiencing crosswinds

In a crosswind scenario, the risk of high-speed trains overturning increases when they run on viaducts since the aerodynamic loads are higher than on the ground. In order to increase safety, vehicles are sheltered by fences that are installed on the viaduct to reduce the loads experienced by the train. Windbreaks can be designed to have different heights, and with or without eaves on the top. In this paper, a parametric study with a total of 12 fence designs was carried out using a two-dimensional model of a train standing on a viaduct. To asses the relative effectiveness of sheltering devices, tests were done in a wind tunnel with a scaled model at a Reynolds number of 1 × 105, and the train’s aerodynamic coefficients were measured. Experimental results were compared with those predicted by Unsteady Reynolds-averaged Navier-Stokes (URANS) simulations of flow, showing that a computational model is able to satisfactorily predict the trend of the aerodynamic coefficients. In a second set of tests, the Reynolds number was increased to 12 × 106 (at a free flow air velocity of 30 m/s) in order to simulate strong wind conditions. The aerodynamic coefficients showed a similar trend for both Reynolds numbers; however, their numerical value changed enough to indicate that simulations at the lower Reynolds number do not provide all required information. Furthermore, the variation of coefficients in the simulations allowed an explanation of how fences modified the flow around the vehicle to be proposed. This made it clear why increasing fence height reduced all the coefficients but adding an eave had an effect mainly on the lift force coefficient. Finally, by analysing the time signals it was possible to clarify the influence of the Reynolds number on the peak-to-peak amplitude, the time period and the Strouhal number

A 2D computational parametric analysis of the sheltering effect of fences on a railway vehicle standing on a bridge and experiencing crosswinds

In a crosswind scenario, the risk of high-speed trains overturning increases when they run on viaducts since the aerodynamic loads are higher than on the ground. In order to increase safety, vehicles are sheltered by fences that are installed on the viaduct to reduce the loads experienced by the train. Windbreaks can be designed to have different heights, and with or without eaves on the top. In this paper, a parametric study with a total of 12 fence designs was carried out using a two-dimensional model of a train standing on a viaduct. To asses the relative effectiveness of sheltering devices, tests were done in a wind tunnel with a scaled model at a Reynolds number of 1 × 105, and the train’s aerodynamic coefficients were measured. Experimental results were compared with those predicted by Unsteady Reynolds-averaged Navier-Stokes (URANS) simulations of flow, showing that a computational model is able to satisfactorily predict the trend of the aerodynamic coefficients. In a second set of tests, the Reynolds number was increased to 12 × 106 (at a free flow air velocity of 30 m/s) in order to simulate strong wind conditions. The aerodynamic coefficients showed a similar trend for both Reynolds numbers; however, their numerical value changed enough to indicate that simulations at the lower Reynolds number do not provide all required information. Furthermore, the variation of coefficients in the simulations allowed an explanation of how fences modified the flow around the vehicle to be proposed. This made it clear why increasing fence height reduced all the coefficients but adding an eave had an effect mainly on the lift force coefficient. Finally, by analysing the time signals it was possible to clarify the influence of the Reynolds number on the peak-to-peak amplitude, the time period and the Strouhal number

Tissue diagnosis using power-sharing multifocal Raman micro-spectroscopy and auto-fluorescence imaging

We describe a multifocal Raman micro-spectroscopy detection method based on a digital micromirror device, which allows for simultaneous “power-sharing” acquisition of Raman spectra from ad hoc sampling points. As the locations of the points can be rapidly updated in real-time via software control of a liquid-crystal spatial light modulator (LC-SLM), this technique is compatible with automated adaptive- and selective-sampling Raman spectroscopy techniques, the latter of which has previously been demonstrated for fast diagnosis of skin cancer tissue resections. We describe the performance of this instrument and show examples of multiplexed measurements on a range of test samples. Following this, we show the feasibility of reducing measurement time for power-shared multifocal Raman measurements combined with confocal auto-fluorescence imaging to provide guided diagnosis of tumours in human skin samples

Automated multimodal spectral histopathology for quantitative diagnosis of residual tumour during basal cell carcinoma surgery

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 based on MSH designed to be used in the clinic and operated by a non-specialist spectroscopy user. The algorithms for the AF image processing and Raman spectroscopy classification had been first optimised on a manually-operated laboratory instrument and then validated on the automated prototype using skin samples from independent patients. We present results on a range of skin samples excised during Mohs micrographic surgery, and demonstrate consistent diagnosis obtained in repeat test measurement, in agreement with the reference histopathology diagnosis. We also show that the prototype instrument can be operated by clinical users (a skin surgeon and a core medical trainee, after only 1-8 hours of training) to obtain consistent results in agreement with histopathology. The development of the new automated prototype and demonstration of inter-instrument transferability of the diagnosis models are important steps on the clinical translation path: it allows the testing of the MSH technology in a relevant clinical environment in order to evaluate its performance on a sufficiently large number of patients

Crystallization-Induced Gelling as a Method to 4D Print Low-Water-Content Non-isocyanate Polyurethane Hydrogels

[EN]The use of three-dimensional (3D) printable hydrogels for biomedical applications has attracted considerable attention as a consequence of the ability to precisely define the morphology of the printed object, allowing patients' needs to be targeted. However, the majority of hydrogels do not possess suitable mechanical properties to fulfill an adequate rheological profile for printability, and hence, 3D printing of cross-linked networks is challenging and normally requires postprinting modifications to obtain the desired scaffolds. In this work, we took advantage of the crystallization process of poly(ethylene glycol) to print non-isocyanate poly(hydroxyurethane) hydrogels with tunable mechanical properties. As a consequence of the crystallization process, the hydrogel modulus can be tuned up to 3 orders of magnitude upon heating up to 40 degrees C, offering an interesting strategy to directly 3D-print hydrogels without the need of postprinting cross-linking. Moreover, the absence of any toxicity makes these materials ideal candidates for biomedical applications.The authors acknowledge financial support from the European Commission through SUSPOL-EJD 642671 project. M.C.A. thanks the University of Birmingham for funding

Benefits of Polydopamine as Particle/Matrix Interface in Polylactide/PD-BaSO4 Scaffolds

This work reports the versatility of polydopamine (PD) when applied as a particle coating in a composite of polylactide (PLA). Polydopamine was observed to increase the particle–matrix interface strength and facilitate the adsorption of drugs to the material surface. Here, barium sulfate radiopaque particles were functionalized with polydopamine and integrated into a polylactide matrix, leading to the formulation of a biodegradable and X-ray opaque material with enhanced mechanical properties. Polydopamine functionalized barium sulfate particles also facilitated the adsorption and release of the antibiotic levofloxacin. Analysis of the antibacterial capacity of these composites and the metabolic activity and proliferation of human dermal fibroblasts in vitro demonstrated that these materials are non-cytotoxic and can be 3D printed to formulate complex biocompatible materials for bone fixation devices.The authors express thanks for technical and human support provided by SGIker of UPV/EHU and European funding: European Regional Development Fund (ERDF) and European Social Fund (ESF)