Antoni Homs Corbera - Academia.edu (original) (raw)

Papers by Antoni Homs Corbera

Cancer Research, Apr 4, 2023

Despite recent extraordinary clinical success of immune checkpoint inhibitors (ICIs) in treating ... more Despite recent extraordinary clinical success of immune checkpoint inhibitors (ICIs) in treating people affected by melanoma, a relevant number of patients still develops an adaptive resistance resulting in poor prognosis. To accelerate access to new therapies, there is a strong need for an in vitro human melanoma model mimicking the complexity of the tumor's cellular and physical microenvironment. Such model should recapitulate 3 critical features: (1) a reconstructed human melanoma-in-skin (Mel-RhS) to model melanoma cell invasion, (2) an endothelium to mimic the vascular system, and (3) circulation of, and ultimately, infiltration by, immune cells. Here, we present the development of these 3 individual biological features separately in dynamic conditions. These were constructed in standard multi-well plates (MW) by means of our microenviromentally controlled microphysiological system (MPS) (CubiX). This is a critical step towards the creation of a fully differentiated vascularized immunocompetent metastatic melanoma-on-chip model to recapitulate human pathophysiology, suitable for testing immunotherapies and studying the onset of possible resistance mechanisms. (1) Mel-RhS were constructed on transwells (8 μm pore size) and consisted of a human fibroblasts-populated collagen-fibrin dermal compartment, on top of which A375 melanoma cells and human keratinocytes were seeded. Mel-RhS were air-exposed for > 14 days to form of a fully differentiated and stratified epidermis. Melanoma nests developed and expanded into the dermal compartment in the 3D model, mimicking the initial stages of invasive melanoma. Moreover, Mel-RhS were viable under flow conditions for up to 3 days and their histology was comparable to that of the static controls. (2) The endothelial layer consisted of a monolayer of CD31+ endothelial cells on the bottom side of the transwell membrane. The shear stress provided by medium perfusion was able to induce alignment (75-80%) of cells within 24 hours (3 times faster than published protocols) as well as Von Willebrand Factor production. Real-time pH, lactate, glucose, and oxygen consumption were measured by using in-line sensors during the culture time. (3) Circulation of immune cells (MUTZ-3 progenitor cells) was achieved up to 24 hours in the presence of a healthy reconstructed human skin (RhS) model in a proof-of-concept study. The specific design of the developed MPS allowed for both immune cell flow and collection for downstream phenotypic analysis. In conclusion, we have individually recapitulated these major biological features of melanoma in vitro, in standard MW under dynamic culture conditions. In the future, the integration of these features into a single model would provide a unique in vitro vascularized immunocompetent human melanoma-on-chip model as a novel tool to investigate and test new therapies targeting adaptive resistance to ICIs. Citation Format: Elisabetta Michielon, Tanja de GruIijl, Taco Waaijman, Matteo Boninsegna, Divyasree Prabhakaran, Hadhemi Mejri, Antoni Homs Corbera, Pierre Gaudriault, Susan Gibbs, Dario Fassini. Towards the development of an in vitro human vascularized immunocompetent metastatic melanoma-on-chip model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 155.

Cancer Research

Despite recent extraordinary clinical success of immune checkpoint inhibitors (ICIs) in treating ... more Despite recent extraordinary clinical success of immune checkpoint inhibitors (ICIs) in treating people affected by melanoma, a relevant number of patients still develops an adaptive resistance resulting in poor prognosis. To accelerate access to new therapies, there is a strong need for an in vitro human melanoma model mimicking the complexity of the tumor's cellular and physical microenvironment. Such model should recapitulate 3 critical features: (1) a reconstructed human melanoma-in-skin (Mel-RhS) to model melanoma cell invasion, (2) an endothelium to mimic the vascular system, and (3) circulation of, and ultimately, infiltration by, immune cells. Here, we present the development of these 3 individual biological features separately in dynamic conditions. These were constructed in standard multi-well plates (MW) by means of our microenviromentally controlled microphysiological system (MPS) (CubiX). This is a critical step towards the creation of a fully differentiated vascula...

Cancer Research

Recent advances in immuno-oncology have significantly increased the therapeutic arsenal available... more Recent advances in immuno-oncology have significantly increased the therapeutic arsenal available for clinicians. However, being able to identify the responder to a given treatment remains difficult and time consuming. This is due to the lack of translational preclinical models that recapitulate the complete cellular and physical tumor-immune micro-environment (TME). We report for the first time a high throughput vascularized immunocompetent breast tumoroids model in standard multiwell culture plate (MW). The model uses micro physiological system (MPS) and microfabrication to recapitulate and precisely control the TME. The tumor model includes fibroblasts, tumor cells (MDA-MB-231), immune cells (CD81+, CD64+), endothelial cells (CD31+), and a collagen extra cellular matrix. These are essential for the TME and are often lacking in preclinical models, potentially biasing the observed therapeutic response. The physical microenvironment was recapitulated using Cherry Biotech’s MPS, Cubi...

In this work, we report the detection of proteins by means of simultaneous fluorescence and imped... more In this work, we report the detection of proteins by means of simultaneous fluorescence and impedance measurements in a cyclo olefin polymer (COP) chip containing an ordered pillar array column, used for reversed-phase liquid chromatography, with integrated microband gold electrodes at the end of the channel.

Sensors and Actuators B: Chemical, 2019

Biosensor devices can constitute an advanced tool for monitoring and study complex dynamic biolog... more Biosensor devices can constitute an advanced tool for monitoring and study complex dynamic biolog ical processes, as for example cellular adhesion. Cellular adhesion is a multipart process with crucial implications in physiology (i.e. immune response, tissue nature, architecture maintenance, or behavior and expansion of tumor cells). This work focuses on offering a controlled methodology in order to fabricate a flexible plasmo-nanomechanical biosensor placed within a microfluidic channel as a new tool for future cell adhesion studies. We designed, fabricated, and optically and mechanically characterized this novel optical biosensor. As a proof-of-concept of its functionality, the biosensor was employed to observe fibroblasts adhesion in a cell culture. The device is configured by an hexagonal array of flexible rigid/soft polymeric nanopillars capped with plasmonic gold nanodisks integrated inside a microfluidic channel. The fabrication employs low-cost and large-scale replica molding techniques using two different polymers materials (EPOTECK OG142 and 310M). By using those materials the spring constant of the polymer nanopillars (k) can be fabricated from 1.19E-02 [N/m] to 5.35E +00 [N/m] indicating different mechanical sensitivities to shear stress. Therefore, the biosensor has the feasibility to mimic soft and rigid tissues important for the description of cellular nanoscale behaviours. The biosensor exhibits a suitable bulk sensitivity of 164 nm or 206 nm/refractive index unit respectively, depending on the base material. The range of calculated forces goes from ≈1.98 nN to ≈.942 µN. This supports that the plasmo-nanomechanical biosensors could be employed as novel tool to study living cells behavior.

Organ-on-a-chip

Abstract Heart diseases, such as myocardial infarction, hypertrophy, and atherosclerosis, are the... more Abstract Heart diseases, such as myocardial infarction, hypertrophy, and atherosclerosis, are the highest worldwide death cause, being an important focus for new treatments development. Furthermore, half of the drugs retracted from the market in the last 30 years induced heart electrophysiological disfunctions and muscular damage resulting from their side effects. This highlights the limitations of currently used drug testing methods to evaluate the effect of compounds on the heart functionality. Myocardium therapies and cardiotoxicity are currently studied using two-dimensional (2D) static cultures of cardiomyocytes or, alternatively, animal models. 2D cell cultures are oversimplified and fail to reproduce cell orientation as well as cardiac tissue physiology, whereas animal models have demonstrated to be not enough efficient in predicting human responses. Cardiovascular in vitro models are highly desirable due to their relative lower costs, due to their potential to better mimic human physiology by using human cells and due to the societal concerns on animal testing. However, the complex dynamics are a strong limiting factor when aiming to capture the heart main physiological functions in an in vitro model. The conventional 2D cardiovascular in vitro models cannot replicate physiological conditions, which are conditioned by physical stimulations, such as electrical signaling, mechanic strain, or shear stress, that are important factors in setting the alignment, structure, and phenotype of cardiac cells. Microfluidics, and by extension organ-on-chip devices, are highly versatile and potentially suitable to provide continuous media perfusion to cells, allowing to control shear stresses, and to architect specific spatial distributions of different cell types. Furthermore, they can be also easily integrated with other technologies to provide cells with stimulus of different natures such as mechanical or electrical ones.

Biosensors and Bioelectronics, 2016

L'aportacio mes important d'aquesta tesi doctoral es la proposta de noves tecniques de pr... more L'aportacio mes important d'aquesta tesi doctoral es la proposta de noves tecniques de processament del senyal per a l'analisi objectiu d'uns tipus de sons respiratoris, anomenats sibilancies, com a eina complementaria pel diagnostic medic i pel seguiment clinic de malalties pulmonars. Per a detectar les sibilancies, inicialment s'han proposat i validat dos algorismes basats en l'analisi de l'espectrograma del senyal: el Shabtai-Musih de Mitjana Local (SMML) i l'Algorisme de Deteccio de Sibilancies Adaptatiu Local (LAWDA). La validacio, realitzada a partir de 60 senyals de so amb l'ajut d'un metge especialista, ha mostrat una sensibilitat en la deteccio de sibilancies del 90.3% pel SMML i del 93.9% pel LAWDA en el tram de flux de l'espiracio forcada compres entre 1.2 i 0.2 l/s. Pel tram de flux de 0.2 a 0 l/s els valors han estat del 64.5% i del 71.0% respectivament. Per a l'estudi s'han fet servir senyals de so adquirits durant la...

Chip-based optical nanoscopy, relying on single molecule localization microscopy has recently bee... more Chip-based optical nanoscopy, relying on single molecule localization microscopy has recently been demonstrated to reach 70 nm lateral resolution over wide fields of view (500 µm x 500 µm). To make this technique more sustainable for live-cell imaging we embedded a photonic chip into a microfluidic support that is able to perfuse and thermalize the samples. In this way specimens are maintained under physiological conditions during the imaging which can be a timeconsuming process. The system consists of a multilayer chip with the size of a glass coverslip (60 mm × 24 mm). The sample is illuminated using waveguides that are fabricated from high refractive index material. The waveguide hosts a chamber (17.3 μl) where cells are seeded and perfused with medium. A thin layer (188 µm) of cyclic olefin polymer (COP) seals the chamber and allows optical image acquisition. A thermalizing solution is perfused from the bottom to accurately warm up/cool down the waveguide in a range of 5°C - 45°...

Resumen del trabajo presentado al VIII International Congress on Analytical Nanoscience and Nanot... more Resumen del trabajo presentado al VIII International Congress on Analytical Nanoscience and Nanotechnology, celebrado en Barcelona (Espana) del 3 al 5 de julio de 2017.

Constant evolution and improvements on areas such as tissue engineering, microfluidics and nanote... more Constant evolution and improvements on areas such as tissue engineering, microfluidics and nanotechnology have made it possible to partially close the gap between conventional in vitro cell cultures and animal model-based studies. A step forward in this field concerns organ-on-chip technologies, capable of reproducing the most relevant physiological features of an organ in a microfluidic platform. In this work we have exploited the capabilities of laminar co-flow inside our biomimetic platform, the splenon-on-a-chip, in order to enhance cell culture inside its channels to better mimic the spleen's environment.

Open Research Europe

It is difficult to model in vitro the intestine when seeking to include crosstalk with the gut mi... more It is difficult to model in vitro the intestine when seeking to include crosstalk with the gut microbiota, immune and neuroendocrine systems. Here we present a roadmap of the current models to facilitate the choice in preclinical and translational research with a focus on gut-on-chip. These micro physiological systems (MPS) are microfluidic devices that recapitulate in vitro the physiology of the intestine. We reviewed the gut-on-chips that had been developed in academia and industries as single chip and that have three main purpose: replicate the intestinal physiology, the intestinal pathological features, and for pharmacological tests.

Open Research Europe

Microphysiological systems describe the use of divergent technologies to recapitulate complex phy... more Microphysiological systems describe the use of divergent technologies to recapitulate complex physiology in vitro convergently in a cruelty and animal free manner. The technologies aim towards enabling researchers from academia and industry to conduct more ethical and cost-effective research and development, preclinical and translational, and to advance related fields such as precision medicine. However, projected markets appear relatively small compared to related markets, where regulatory implementation and reluctant end-user adoption creates uncertainty for the emerging technologies with associated technological maturity. Regardless of this, companies surpassed and expanded successfully beyond the predicted five-year survival rate through strategic technology- and business development through collaboration and partnerships. A hallmark of the companies is a core competency or unique intellectual property coupled with securing early investment and interest from industry role-player...

RSC Advances

The control of the morphology, as well as the physical and chemical properties, of nanopores is a... more The control of the morphology, as well as the physical and chemical properties, of nanopores is a key issue for many applications.

Sensors and Actuators A: Physical

Journal of Biophotonics

Ultrasmooth gold/silver/gold trilayer nanostructured plasmonic sensors were obtained using commer... more Ultrasmooth gold/silver/gold trilayer nanostructured plasmonic sensors were obtained using commercial Blu-ray optical discs as nanoslits-based flexible polymer substrates. A thin gold film was used as an adhesion and nucleation layer to improve the chemical stability and reduce the surface roughness of the overlying silver film, without increasing ohmic plasmon losses. The structures were physically and optically characterized and compared with nanostructures of single gold layer. Ultrasmooth and chemically stable trilayer nanostructures with a surface roughness <0.5 nm were obtained following a simple and reproducible fabrication process. They showed a Figure of Merit (FOM) value up to 69.2 RIU-1 which is significantly higher (more than 95%) than the gold monolayer counterpart. Their potential for biosensing was demonstrated by employing the trilayer sensor for the direct and label-free detection of CRP protein biomarker in undiluted urine achieving a LOD in the pM order.

Journal of Microelectromechanical Systems

Biosensors & bioelectronics, Jan 10, 2017

Nanostructure-based plasmonic biosensors have quickly positioned themselves as interesting candid... more Nanostructure-based plasmonic biosensors have quickly positioned themselves as interesting candidates for the design of portable optical biosensor platforms considering the potential benefits they can offer in integration, miniaturization, multiplexing, and real-time label-free detection. We have developed a simple integrated nanoplasmonic sensor taking advantage of the periodic nanostructured array of commercial Blu-ray discs. Sensors with two gold film thicknesses (50 and 100nm) were fabricated and optically characterized by varying the oblique-angle of the incident light in optical reflectance measurements. Contrary to the use normal light incidence previously reported with other optical discs, we observed an enhancement in sensitivity and a narrowing of the resonant linewidths as the light incidence angle was increased, which could be related to the generation of Fano resonant modes. The new sensors achieve a figure of merit (FOM) up to 35 RIU(-1) and a competitive bulk limit of...

Sensors, 2016

Bacteria concentration and detection is time-consuming in regular microbiology procedures aimed t... more Bacteria concentration and detection is time-consuming in regular microbiology procedures aimed to facilitate the detection and analysis of these cells at very low concentrations. Traditional methods are effective but often require several days to complete. This scenario results in low bioanalytical and diagnostic methodologies with associated increased costs and complexity. In recent years, the exploitation of the intrinsic electrical properties of cells has emerged as an appealing alternative approach for concentrating and detecting bacteria. The combination of dielectrophoresis (DEP) and impedance analysis (IA) in microfluidic on-chip platforms could be key to develop rapid, accurate, portable, simple-to-use and cost-effective microfluidic devices with a promising impact in medicine, public health, agricultural, food control and environmental areas. The present document reviews recent DEP and IA combined approaches and the latest relevant improvements focusing on bacteria concentration and detection, including selectivity, sensitivity, detection time, and conductivity variation enhancements. Furthermore, this review analyses future trends and challenges which need to be addressed in order to successfully commercialize these platforms resulting in an adequate social return of public-funded investments.

Cancer Research, Apr 4, 2023

Despite recent extraordinary clinical success of immune checkpoint inhibitors (ICIs) in treating ... more Despite recent extraordinary clinical success of immune checkpoint inhibitors (ICIs) in treating people affected by melanoma, a relevant number of patients still develops an adaptive resistance resulting in poor prognosis. To accelerate access to new therapies, there is a strong need for an in vitro human melanoma model mimicking the complexity of the tumor's cellular and physical microenvironment. Such model should recapitulate 3 critical features: (1) a reconstructed human melanoma-in-skin (Mel-RhS) to model melanoma cell invasion, (2) an endothelium to mimic the vascular system, and (3) circulation of, and ultimately, infiltration by, immune cells. Here, we present the development of these 3 individual biological features separately in dynamic conditions. These were constructed in standard multi-well plates (MW) by means of our microenviromentally controlled microphysiological system (MPS) (CubiX). This is a critical step towards the creation of a fully differentiated vascularized immunocompetent metastatic melanoma-on-chip model to recapitulate human pathophysiology, suitable for testing immunotherapies and studying the onset of possible resistance mechanisms. (1) Mel-RhS were constructed on transwells (8 μm pore size) and consisted of a human fibroblasts-populated collagen-fibrin dermal compartment, on top of which A375 melanoma cells and human keratinocytes were seeded. Mel-RhS were air-exposed for &gt; 14 days to form of a fully differentiated and stratified epidermis. Melanoma nests developed and expanded into the dermal compartment in the 3D model, mimicking the initial stages of invasive melanoma. Moreover, Mel-RhS were viable under flow conditions for up to 3 days and their histology was comparable to that of the static controls. (2) The endothelial layer consisted of a monolayer of CD31+ endothelial cells on the bottom side of the transwell membrane. The shear stress provided by medium perfusion was able to induce alignment (75-80%) of cells within 24 hours (3 times faster than published protocols) as well as Von Willebrand Factor production. Real-time pH, lactate, glucose, and oxygen consumption were measured by using in-line sensors during the culture time. (3) Circulation of immune cells (MUTZ-3 progenitor cells) was achieved up to 24 hours in the presence of a healthy reconstructed human skin (RhS) model in a proof-of-concept study. The specific design of the developed MPS allowed for both immune cell flow and collection for downstream phenotypic analysis. In conclusion, we have individually recapitulated these major biological features of melanoma in vitro, in standard MW under dynamic culture conditions. In the future, the integration of these features into a single model would provide a unique in vitro vascularized immunocompetent human melanoma-on-chip model as a novel tool to investigate and test new therapies targeting adaptive resistance to ICIs. Citation Format: Elisabetta Michielon, Tanja de GruIijl, Taco Waaijman, Matteo Boninsegna, Divyasree Prabhakaran, Hadhemi Mejri, Antoni Homs Corbera, Pierre Gaudriault, Susan Gibbs, Dario Fassini. Towards the development of an in vitro human vascularized immunocompetent metastatic melanoma-on-chip model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 155.

Cancer Research

Despite recent extraordinary clinical success of immune checkpoint inhibitors (ICIs) in treating ... more Despite recent extraordinary clinical success of immune checkpoint inhibitors (ICIs) in treating people affected by melanoma, a relevant number of patients still develops an adaptive resistance resulting in poor prognosis. To accelerate access to new therapies, there is a strong need for an in vitro human melanoma model mimicking the complexity of the tumor's cellular and physical microenvironment. Such model should recapitulate 3 critical features: (1) a reconstructed human melanoma-in-skin (Mel-RhS) to model melanoma cell invasion, (2) an endothelium to mimic the vascular system, and (3) circulation of, and ultimately, infiltration by, immune cells. Here, we present the development of these 3 individual biological features separately in dynamic conditions. These were constructed in standard multi-well plates (MW) by means of our microenviromentally controlled microphysiological system (MPS) (CubiX). This is a critical step towards the creation of a fully differentiated vascula...

Cancer Research

Recent advances in immuno-oncology have significantly increased the therapeutic arsenal available... more Recent advances in immuno-oncology have significantly increased the therapeutic arsenal available for clinicians. However, being able to identify the responder to a given treatment remains difficult and time consuming. This is due to the lack of translational preclinical models that recapitulate the complete cellular and physical tumor-immune micro-environment (TME). We report for the first time a high throughput vascularized immunocompetent breast tumoroids model in standard multiwell culture plate (MW). The model uses micro physiological system (MPS) and microfabrication to recapitulate and precisely control the TME. The tumor model includes fibroblasts, tumor cells (MDA-MB-231), immune cells (CD81+, CD64+), endothelial cells (CD31+), and a collagen extra cellular matrix. These are essential for the TME and are often lacking in preclinical models, potentially biasing the observed therapeutic response. The physical microenvironment was recapitulated using Cherry Biotech’s MPS, Cubi...

In this work, we report the detection of proteins by means of simultaneous fluorescence and imped... more In this work, we report the detection of proteins by means of simultaneous fluorescence and impedance measurements in a cyclo olefin polymer (COP) chip containing an ordered pillar array column, used for reversed-phase liquid chromatography, with integrated microband gold electrodes at the end of the channel.

Sensors and Actuators B: Chemical, 2019

Biosensor devices can constitute an advanced tool for monitoring and study complex dynamic biolog... more Biosensor devices can constitute an advanced tool for monitoring and study complex dynamic biolog ical processes, as for example cellular adhesion. Cellular adhesion is a multipart process with crucial implications in physiology (i.e. immune response, tissue nature, architecture maintenance, or behavior and expansion of tumor cells). This work focuses on offering a controlled methodology in order to fabricate a flexible plasmo-nanomechanical biosensor placed within a microfluidic channel as a new tool for future cell adhesion studies. We designed, fabricated, and optically and mechanically characterized this novel optical biosensor. As a proof-of-concept of its functionality, the biosensor was employed to observe fibroblasts adhesion in a cell culture. The device is configured by an hexagonal array of flexible rigid/soft polymeric nanopillars capped with plasmonic gold nanodisks integrated inside a microfluidic channel. The fabrication employs low-cost and large-scale replica molding techniques using two different polymers materials (EPOTECK OG142 and 310M). By using those materials the spring constant of the polymer nanopillars (k) can be fabricated from 1.19E-02 [N/m] to 5.35E +00 [N/m] indicating different mechanical sensitivities to shear stress. Therefore, the biosensor has the feasibility to mimic soft and rigid tissues important for the description of cellular nanoscale behaviours. The biosensor exhibits a suitable bulk sensitivity of 164 nm or 206 nm/refractive index unit respectively, depending on the base material. The range of calculated forces goes from ≈1.98 nN to ≈.942 µN. This supports that the plasmo-nanomechanical biosensors could be employed as novel tool to study living cells behavior.

Organ-on-a-chip

Abstract Heart diseases, such as myocardial infarction, hypertrophy, and atherosclerosis, are the... more Abstract Heart diseases, such as myocardial infarction, hypertrophy, and atherosclerosis, are the highest worldwide death cause, being an important focus for new treatments development. Furthermore, half of the drugs retracted from the market in the last 30 years induced heart electrophysiological disfunctions and muscular damage resulting from their side effects. This highlights the limitations of currently used drug testing methods to evaluate the effect of compounds on the heart functionality. Myocardium therapies and cardiotoxicity are currently studied using two-dimensional (2D) static cultures of cardiomyocytes or, alternatively, animal models. 2D cell cultures are oversimplified and fail to reproduce cell orientation as well as cardiac tissue physiology, whereas animal models have demonstrated to be not enough efficient in predicting human responses. Cardiovascular in vitro models are highly desirable due to their relative lower costs, due to their potential to better mimic human physiology by using human cells and due to the societal concerns on animal testing. However, the complex dynamics are a strong limiting factor when aiming to capture the heart main physiological functions in an in vitro model. The conventional 2D cardiovascular in vitro models cannot replicate physiological conditions, which are conditioned by physical stimulations, such as electrical signaling, mechanic strain, or shear stress, that are important factors in setting the alignment, structure, and phenotype of cardiac cells. Microfluidics, and by extension organ-on-chip devices, are highly versatile and potentially suitable to provide continuous media perfusion to cells, allowing to control shear stresses, and to architect specific spatial distributions of different cell types. Furthermore, they can be also easily integrated with other technologies to provide cells with stimulus of different natures such as mechanical or electrical ones.

Biosensors and Bioelectronics, 2016

L'aportacio mes important d'aquesta tesi doctoral es la proposta de noves tecniques de pr... more L'aportacio mes important d'aquesta tesi doctoral es la proposta de noves tecniques de processament del senyal per a l'analisi objectiu d'uns tipus de sons respiratoris, anomenats sibilancies, com a eina complementaria pel diagnostic medic i pel seguiment clinic de malalties pulmonars. Per a detectar les sibilancies, inicialment s'han proposat i validat dos algorismes basats en l'analisi de l'espectrograma del senyal: el Shabtai-Musih de Mitjana Local (SMML) i l'Algorisme de Deteccio de Sibilancies Adaptatiu Local (LAWDA). La validacio, realitzada a partir de 60 senyals de so amb l'ajut d'un metge especialista, ha mostrat una sensibilitat en la deteccio de sibilancies del 90.3% pel SMML i del 93.9% pel LAWDA en el tram de flux de l'espiracio forcada compres entre 1.2 i 0.2 l/s. Pel tram de flux de 0.2 a 0 l/s els valors han estat del 64.5% i del 71.0% respectivament. Per a l'estudi s'han fet servir senyals de so adquirits durant la...

Chip-based optical nanoscopy, relying on single molecule localization microscopy has recently bee... more Chip-based optical nanoscopy, relying on single molecule localization microscopy has recently been demonstrated to reach 70 nm lateral resolution over wide fields of view (500 µm x 500 µm). To make this technique more sustainable for live-cell imaging we embedded a photonic chip into a microfluidic support that is able to perfuse and thermalize the samples. In this way specimens are maintained under physiological conditions during the imaging which can be a timeconsuming process. The system consists of a multilayer chip with the size of a glass coverslip (60 mm × 24 mm). The sample is illuminated using waveguides that are fabricated from high refractive index material. The waveguide hosts a chamber (17.3 μl) where cells are seeded and perfused with medium. A thin layer (188 µm) of cyclic olefin polymer (COP) seals the chamber and allows optical image acquisition. A thermalizing solution is perfused from the bottom to accurately warm up/cool down the waveguide in a range of 5°C - 45°...

Resumen del trabajo presentado al VIII International Congress on Analytical Nanoscience and Nanot... more Resumen del trabajo presentado al VIII International Congress on Analytical Nanoscience and Nanotechnology, celebrado en Barcelona (Espana) del 3 al 5 de julio de 2017.

Constant evolution and improvements on areas such as tissue engineering, microfluidics and nanote... more Constant evolution and improvements on areas such as tissue engineering, microfluidics and nanotechnology have made it possible to partially close the gap between conventional in vitro cell cultures and animal model-based studies. A step forward in this field concerns organ-on-chip technologies, capable of reproducing the most relevant physiological features of an organ in a microfluidic platform. In this work we have exploited the capabilities of laminar co-flow inside our biomimetic platform, the splenon-on-a-chip, in order to enhance cell culture inside its channels to better mimic the spleen's environment.

Open Research Europe

It is difficult to model in vitro the intestine when seeking to include crosstalk with the gut mi... more It is difficult to model in vitro the intestine when seeking to include crosstalk with the gut microbiota, immune and neuroendocrine systems. Here we present a roadmap of the current models to facilitate the choice in preclinical and translational research with a focus on gut-on-chip. These micro physiological systems (MPS) are microfluidic devices that recapitulate in vitro the physiology of the intestine. We reviewed the gut-on-chips that had been developed in academia and industries as single chip and that have three main purpose: replicate the intestinal physiology, the intestinal pathological features, and for pharmacological tests.

Open Research Europe

Microphysiological systems describe the use of divergent technologies to recapitulate complex phy... more Microphysiological systems describe the use of divergent technologies to recapitulate complex physiology in vitro convergently in a cruelty and animal free manner. The technologies aim towards enabling researchers from academia and industry to conduct more ethical and cost-effective research and development, preclinical and translational, and to advance related fields such as precision medicine. However, projected markets appear relatively small compared to related markets, where regulatory implementation and reluctant end-user adoption creates uncertainty for the emerging technologies with associated technological maturity. Regardless of this, companies surpassed and expanded successfully beyond the predicted five-year survival rate through strategic technology- and business development through collaboration and partnerships. A hallmark of the companies is a core competency or unique intellectual property coupled with securing early investment and interest from industry role-player...

RSC Advances

The control of the morphology, as well as the physical and chemical properties, of nanopores is a... more The control of the morphology, as well as the physical and chemical properties, of nanopores is a key issue for many applications.

Sensors and Actuators A: Physical

Journal of Biophotonics

Ultrasmooth gold/silver/gold trilayer nanostructured plasmonic sensors were obtained using commer... more Ultrasmooth gold/silver/gold trilayer nanostructured plasmonic sensors were obtained using commercial Blu-ray optical discs as nanoslits-based flexible polymer substrates. A thin gold film was used as an adhesion and nucleation layer to improve the chemical stability and reduce the surface roughness of the overlying silver film, without increasing ohmic plasmon losses. The structures were physically and optically characterized and compared with nanostructures of single gold layer. Ultrasmooth and chemically stable trilayer nanostructures with a surface roughness <0.5 nm were obtained following a simple and reproducible fabrication process. They showed a Figure of Merit (FOM) value up to 69.2 RIU-1 which is significantly higher (more than 95%) than the gold monolayer counterpart. Their potential for biosensing was demonstrated by employing the trilayer sensor for the direct and label-free detection of CRP protein biomarker in undiluted urine achieving a LOD in the pM order.

Journal of Microelectromechanical Systems

Biosensors & bioelectronics, Jan 10, 2017

Nanostructure-based plasmonic biosensors have quickly positioned themselves as interesting candid... more Nanostructure-based plasmonic biosensors have quickly positioned themselves as interesting candidates for the design of portable optical biosensor platforms considering the potential benefits they can offer in integration, miniaturization, multiplexing, and real-time label-free detection. We have developed a simple integrated nanoplasmonic sensor taking advantage of the periodic nanostructured array of commercial Blu-ray discs. Sensors with two gold film thicknesses (50 and 100nm) were fabricated and optically characterized by varying the oblique-angle of the incident light in optical reflectance measurements. Contrary to the use normal light incidence previously reported with other optical discs, we observed an enhancement in sensitivity and a narrowing of the resonant linewidths as the light incidence angle was increased, which could be related to the generation of Fano resonant modes. The new sensors achieve a figure of merit (FOM) up to 35 RIU(-1) and a competitive bulk limit of...

Sensors, 2016

Bacteria concentration and detection is time-consuming in regular microbiology procedures aimed t... more Bacteria concentration and detection is time-consuming in regular microbiology procedures aimed to facilitate the detection and analysis of these cells at very low concentrations. Traditional methods are effective but often require several days to complete. This scenario results in low bioanalytical and diagnostic methodologies with associated increased costs and complexity. In recent years, the exploitation of the intrinsic electrical properties of cells has emerged as an appealing alternative approach for concentrating and detecting bacteria. The combination of dielectrophoresis (DEP) and impedance analysis (IA) in microfluidic on-chip platforms could be key to develop rapid, accurate, portable, simple-to-use and cost-effective microfluidic devices with a promising impact in medicine, public health, agricultural, food control and environmental areas. The present document reviews recent DEP and IA combined approaches and the latest relevant improvements focusing on bacteria concentration and detection, including selectivity, sensitivity, detection time, and conductivity variation enhancements. Furthermore, this review analyses future trends and challenges which need to be addressed in order to successfully commercialize these platforms resulting in an adequate social return of public-funded investments.