3-D polymeric microfluidic devices for BioMOEMS applications

11 páginas, 12 figuras.-- Trabajo presentado en la conferencia "Bioengineered and Bioinspired Systems II"; Sevilla (España); 09-Mayo-2005; Editores: Ricardo A. Carmona, Gustavo Linan-Cembrano.This paper describes the fabrication, packaging and characterization of novel multilayer polymer microfluidic systems fabricated by a CMOS compatible process. These microfluidic devices were specially designed for BioMOEMS applications. Embedded multilayer rectangular smooth and uniform microchannels, 50 to 150 mm wide and 18mm deep were studied. Steady-state flow rates and pressure driven flow control were measured in the laminar flow regime. Flow rates ranging from 1 to 100 µl/min, at pressure drop ranging from 10 to 600 kPa, were obtained. These flow rates yield Reynolds numbers (Re) up to 20. Results indicate that the experimental Re and the flow friction coefficient (f) are in good agreement with the laminar flow theory. These experimental results facilitate the future designs of different microfluidic devices designed by using classical fluidic theory. We also present two different methods developed for macro/microfluidic packaging in order to connect these microfluidic devices to the macroscopic world. The microsystem packaging can withstand pressure drops up from 500 to 2000 kPa with any liquid leakage.This research is sponsored by the Basque and Spanish Governments, under the Torres Quevedo Spanish Fellowship for industrial research and the strategic research program on micro and nanotechnologies (MICROGUNE).Peer reviewe

Severity dependent distribution of impairments in PSP and CBS: Interactive visualizations

BACKGROUND: Progressive supranuclear palsy (PSP) -Richardson's Syndrome and Corticobasal Syndrome (CBS) are the two classic clinical syndromes associated with underlying four repeat (4R) tau pathology. The PSP Rating Scale is a commonly used assessment in PSP clinical trials; there is an increasing interest in designing combined 4R tauopathy clinical trials involving both CBS and PSP. OBJECTIVES: To determine contributions of each domain of the PSP Rating Scale to overall severity and characterize the probable sequence of clinical progression of PSP as compared to CBS. METHODS: Multicenter clinical trial and natural history study data were analyzed from 545 patients with PSP and 49 with CBS. Proportional odds models were applied to model normalized cross-sectional PSP Rating Scale, estimating the probability that a patient would experience impairment in each domain using the PSP Rating Scale total score as the index of overall disease severity. RESULTS: The earliest symptom domain to demonstrate impairment in PSP patients was most likely to be Ocular Motor, followed jointly by Gait/Midline and Daily Activities, then Limb Motor and Mentation, and finally Bulbar. For CBS, Limb Motor manifested first and ocular showed less probability of impairment throughout the disease spectrum. An online tool to visualize predicted disease progression was developed to predict relative disability on each subscale per overall disease severity. CONCLUSION: The PSP Rating Scale captures disease severity in both PSP and CBS. Modelling how domains change in relation to one other at varying disease severities may facilitate detection of therapeutic effects in future clinical trials

3-D polymeric microfluidic devices for BioMOEMS applications

11 páginas, 12 figuras.-- Trabajo presentado en la conferencia "Bioengineered and Bioinspired Systems II"; Sevilla (España); 09-Mayo-2005; Editores: Ricardo A. Carmona, Gustavo Linan-Cembrano.This paper describes the fabrication, packaging and characterization of novel multilayer polymer microfluidic systems fabricated by a CMOS compatible process. These microfluidic devices were specially designed for BioMOEMS applications. Embedded multilayer rectangular smooth and uniform microchannels, 50 to 150 mm wide and 18mm deep were studied. Steady-state flow rates and pressure driven flow control were measured in the laminar flow regime. Flow rates ranging from 1 to 100 µl/min, at pressure drop ranging from 10 to 600 kPa, were obtained. These flow rates yield Reynolds numbers (Re) up to 20. Results indicate that the experimental Re and the flow friction coefficient (f) are in good agreement with the laminar flow theory. These experimental results facilitate the future designs of different microfluidic devices designed by using classical fluidic theory. We also present two different methods developed for macro/microfluidic packaging in order to connect these microfluidic devices to the macroscopic world. The microsystem packaging can withstand pressure drops up from 500 to 2000 kPa with any liquid leakage.This research is sponsored by the Basque and Spanish Governments, under the Torres Quevedo Spanish Fellowship for industrial research and the strategic research program on micro and nanotechnologies (MICROGUNE).Peer reviewe

Síntomas no motores y motores en la enfermedad de Parkinson y su relación con la calidad de vida y los distintos subgrupos clínicos

Resumen: Objetivos: El objetivo del presente trabajo es contrastar la influencia que presentan los síntomas motores y no motores en la calidad de vida de los pacientes con enfermedad de Parkinson (EP), y observar la asociación entre ambos tipos de síntomas. Material y métodos: Estudio transversal que incluye 103 pacientes con EP (55 hombres y 48 mujeres). La calidad de vida fue estudiada con la escala 39-Item Parkinson's Disease Questionnaire (PDQ-39). También se administró la escala Unified Parkinson's Disease Rating Scale (UPDRS I-IV), agrupando diferentes ítems para analizar la presencia de temblor, rigidez, bradicinesia y síntomas axiales para definir los subgrupos clínicos. Para valorar los síntomas no motores, administramos la non-motor symptoms scale (NMSS). Se hicieron estudios de correlación entre las diferentes escalas para ver la influencia sobre la calidad de vida de síntomas motores y no motores. Resultados: Se observaron correlaciones entre las puntuaciones en el PDQ-39 Summary Index (PDQ-39_SI) y la NMSS (cc: 0,56; p < 0,001), UPDRS III (cc: 0,44; p < 0,001) y con la UPDRS IV; (cc: 0,37; p < 0,001). La mayor relación correspondía a los síntomas cognitivos y del estado de ánimo. Existe relación directa entre la puntuación en la NMSS y los síntomas axiales (cc: 0,384; p < 0,01); bradicinesia (cc: 0,299; p < 0,01) y en menor medida rigidez (cc: 0,194; p < 0,05). No se observó ninguna relación entre la presencia de temblor y la puntuación en la NMSS. Conclusión: Hay un mayor peso de los síntomas cognitivos y del estado de ánimo sobre la calidad de vida de los pacientes con EP. Hay al menos 2 fenotipos claramente diferenciados uno con predominancia de síntomas axiales donde hay una gran afectación de síntomas no motores y un fenotipo tremórico con una significativa menor presencia de los mismos. Abstract: Introduction: The aim of the present study is to analyse the influence that motor and non-motor symptoms have on the quality of life (QoL) of patients with Parkinson's disease (PD), and to study the relationship between the two types of symptoms. Material and methods: This cross-sectional study included 103 patients with PD (55 men and 48 women). Quality of life was measured on the PDQ-39 scale. The UPDRS scale (I-IV) was also used, and different items were grouped to analyse the presence of tremor, rigidity, bradykinesia, and axial symptoms. The non-motor symptoms scale (NMSS) was administered to assess non-motor symptoms. We performed correlation analyses between different scales to analyse the influence of motor and non-motor symptoms on QoL. Results: Correlations were observed between the PDQ-39 summary index (PDQ39_SI) and the NMSS (correlation coefficient [cc], 0.56; p < .001), UPDRS III (cc, 0.44; p <  .001) and UPDRS IV (cc, 0.37; p < .001) scores. The strongest correlation was between cognitive symptoms and mood. The analysis pointed to a direct relationship between the NMSS score and axial symptoms (cc, 0.384; p < .01), bradykinesia (cc, 0.299; p < .01), and to a lesser extent, rigidity (cc, 0.194; p < .05). No relationship was observed between presence of tremor and the NMSS score. Conclusion: Cognitive symptoms and mood exert the most influence on QoL of patients with PD. We found at least two phenotypes; one with predominantly axial symptoms, with significant involvement of non-motor symptoms, and a tremor-associated phenotype in which these symptoms are less prevalent. Palabras clave: Enfermedad de Parkinson, Non-motor symptoms scale, Calidad de vida, Keywords: Parkinson's disease, NMSS scale, Quality of lif

Motor and non-motor symptoms of Parkinson's disease and their impact on quality of life and on different clinical subgroups

Introduction: The aim of the present study is to analyse the influence that motor and non-motor symptoms have on the quality of life (QoL) of patients with Parkinson's disease (PD), and to study the relationship between the two types of symptoms. Material and methods: This cross-sectional study included 103 patients with PD (55 men and 48 women). Quality of life was measured on the PDQ-39 scale. The UPDRS scale (I-IV) was also used, and different items were grouped to analyse the presence of tremor, rigidity, bradykinesia, and axial symptoms. The non-motor symptoms scale (NMSS) was administered to assess non-motor symptoms. We performed correlation analyses between different scales to analyse the influence of motor and non-motor symptoms on QoL. Results: Correlations were observed between the PDQ-39 summary index (PDQ39 SI) and the NMSS (correlation coefficient [cc], 0.56; P < .001), UPDRS III (cc, 0.44; P < .001) and UPDRS IV (cc, 0.37; P < .001) scores. The strongest correlation was between cognitive symptoms and mood. The analysis pointed to a direct relationship between the NMSS score and axial symptoms (cc, 0.384; P < .01), bradykinesia (cc, 0.299; P < .01), and to a lesser extent, rigidity (cc, 0.194; P < .05). No relationship was observed between presence of tremor and the NMSS score. Conclusion: Cognitive symptoms and mood exert the most influence on QoL of patients with PD. We found at least two phenotypes; one with predominantly axial symptoms, with significant involvement of non-motor symptoms, and a tremor-associated phenotype in which these symptoms are less prevalent. Resumen: Objetivos: El objetivo del presente trabajo es contrastar la influencia que presentan los síntomas motores y no motores en la calidad de vida de los pacientes con enfermedad de Parkinson (EP), y observar la asociación entre ambos tipos de síntomas. Material y métodos: Estudio transversal que incluye 103 pacientes con EP (55 hombres y 48 mujeres). La calidad de vida fue estudiada con la escala 39-Item Parkinson's Disease Questionnaire (PDQ-39). También se administró la escala Unified Parkinson's Disease Rating Scale (UPDRS I-IV), agrupando diferentes ítems para analizar la presencia de temblor, rigidez, bradicinesia y síntomas axiales para definir los subgrupos clínicos. Para valorar los síntomas no motores, administramos la non-motor symptoms scale (NMSS). Se hicieron estudios de correlación entre las diferentes escalas para ver la influencia sobre la calidad de vida de síntomas motores y no motores. Resultados: Se observaron correlaciones entre las puntuaciones en el PDQ-39 Summary Index (PDQ-39_SI) y la NMSS (cc: 0,56; p < 0,001), UPDRS III (cc: 0,44; p < 0,001) y con la UPDRS IV; (cc: 0,37; p < 0,001). La mayor relación correspondía a los síntomas cognitivos y del estado de ánimo. Existe relación directa entre la puntuación en la NMSS y los síntomas axiales (cc: 0,384; p < 0,01); bradicinesia (cc: 0,299; p < 0,01) y en menor medida rigidez (cc: 0,194; p < 0,05). No se observó ninguna relación entre la presencia de temblor y la puntuación en la NMSS. Conclusión: Hay un mayor peso de los síntomas cognitivos y del estado de ánimo sobre la calidad de vida de los pacientes con EP. Hay al menos 2 fenotipos claramente diferenciados, uno con predominancia de síntomas axiales donde hay una gran afectación de síntomas no motores y un fenotipo tremórico con una significativa menor presencia de los mismos. Keywords: Parkinson's disease, NMSS scale, Quality of life, Palabras clave: Enfermedad de Parkinson, Non-motor symptoms scale, Calidad de vid

Microfluidic-optical integrated CMOS compatible devices for label-free biochemical sensing

11 páginas, 17 figuras, 1 tabla.The fabrication, characterization and packaging of novel microfluidic-optical integrated biosensors for label-free biochemical detection is presented in this paper. The integrated device consists of a three-dimensional embedded microchannel network fabricated using enhanced CMOS compatible SU-8 multilevel polymer technology on top of a wafer containing Mach-Zehnder Interferometer (MZI) nanophotonic biosensor devices. PMMA housing provides connection to the macro-world and ensures robust leakage-free flow operation of the devices. This macro-microfluidic module can operate at pressure drops up to 1000 kPa. Fluid flow experiments have been performed in order to demonstrate the robustness of our microfluidic devices. The devices have been designed to operate under continuous flow. Steady-state flow rates ranging from 1 to 100 µl min−1 at pressure drops ranging from 10 to 500 kPa were measured in the laminar flow regime. Experimental results are in good agreement with laminar flow theory. The first interferometric sensing measurements are presented in order to demonstrate the functionality of these novel integrated devices for lab-on-a-chip and label-free biosensing applications. A bulk refractive index detection limit of 3.8 × 10−6 was obtained, close to the minimum detected up to now by label-free biosensor devices without microfluidic integration. As far as we know, this is the first time that a label-free biosensor device is integrated within a microfluidic network using a wafer-level CMOS compatible process technology.This research is sponsored by the Basque and Spanish Governments, under a Torres Quevedo Spanish Fellowship for industrial research and the programs of research and development ofmicro and biotechnologies MICROGUNE and BIOGUNE.Peer reviewe

Multiple system atrophy: Clinical, evolutive and histopathological characteristics of a series of cases

Background and objective: Multiple system atrophy is a rare and fatal neurodegenerative disorder, characterized by autonomic dysfunction in association with either parkinsonism or cerebellar signs. The pathologic hallmark is the presence of alpha-synuclein aggregates in oligodendrocytes, forming glial cytoplasmic inclusions. Clinically, it may be difficult to distinguish form other parkinsonisms or ataxias, particularly in the early stages of the disease. In this case series we aim to describe in detail the features of MSA patients. Material and methods: Unified MSA Rating Scale (UMSARS) score, structural and functional imaging and cardiovascular autonomic testing, are summarized since early stages of the disease. Results: UMSARS proved to be useful to perform a follow-up being longitudinal examination essential to stratify risk of poor outcome. Neuropathological diagnosis showed an overlap between parkinsonian and cerebellar subtypes, with some peculiarities that could help to distinguish from other subtypes. Conclusion: A better description of MSA features with standardized test confirmed by means of neuropathological studies could help to increase sensitivity. Resumen: Antecedentes y objetivo: La atrofia multisistémica es un trastorno neurodegenerativo raro y letal que se caracteriza por una disfunción autonómica en asociación con parkinsonismo o signos cerebelosos. La marca anatomopatológica es la presencia de agregados de α-sinucleína en los oligodendrocitos, que forman inclusiones citoplasmáticas gliales. Desde un punto de vista clínico, puede ser difícil de distinguir de otros parkinsonismos o ataxias, particularmente en las primeras etapas de la enfermedad. En esta serie de casos, nuestro objetivo es describir en detalle las características de los pacientes con atrofia multisistémica. Material y métodos: Se resumen los datos objetidos de la puntuación de la Escala de calificación unificada de la atrofia multisistémica (UMSARS), imágenes estructurales y funcionales y las pruebas autonómicas cardiovasculares realizadas desde las primeras etapas de la enfermedad. Resultados: La escala UMSAR demostró ser útil para hacer un seguimiento: el examen longitudinal esencial fue para estratificar el riesgo de peor evolución. El diagnóstico neuropatológico mostró un solapamiento entre los subtipos parkinsoniano y cerebeloso, con algunas peculiaridades que podrían ayudar a distinguir los subtipos. Conclusión: Una mejor descripción de las características de la atrofia multisistémica en casos confirmados mediante neuropatología podría ayudar a aumentar la sensibilidad del diagnóstico