Rapid prototyping of multi-scale biomedical microdevices by combining additive manufacturing technologies

The possibility of designing and manufacturing biomedical microdevices with multiple length-scale geometries can help to promote special interactions both with their environment and with surrounding biological systems. These interactions aim to enhance biocompatibility and overall performance by using biomimetic approaches. In this paper, we present a design and manufacturing procedure for obtaining multi-scale biomedical microsystems based on the combination of two additive manufacturing processes: a conventional laser writer to manufacture the overall device structure, and a direct-laser writer based on two-photon polymerization to yield finer details. The process excels for its versatility, accuracy and manufacturing speed and allows for the manufacture of microsystems and implants with overall sizes up to several millimeters and with details down to sub-micrometric structures. As an application example we have focused on manufacturing a biomedical microsystem to analyze the impact of microtextured surfaces on cell motility. This process yielded a relevant increase in precision and manufacturing speed when compared with more conventional rapid prototyping procedures

The Effect of Patterned Micro-Structure on the Apparent Contact Angle and Three-Dimensional Contact Line

The measurement of the apparent contact angle on structured surfaces is much more difficult to obtain than on smooth surfaces because the pinning of liquid to the roughness has a tremendous influence on the three phase contact line. The results presented here clearly show an apparent contact angle variation along the three phase contact line. Accordingly, not only one value for the apparent contact angle can be provided, but a contact angle distribution or an interval has to be given to characterize the wetting behavior. For measuring the apparent contact angle distribution on regularly structured surfaces, namely micrometric pillars and grooves, an experimental approach is presented and the results are provided. A short introduction into the manufacturing process of such structured surfaces, which is a combination of Direct LASER Writing (DLW) lithography, electroforming and hot embossing shows the high quality standard of the used surfaces

GWAS meta-analysis of over 29,000 people with epilepsy identifies 26 risk loci and subtype-specific genetic architecture

Epilepsy is a highly heritable disorder affecting over 50 million people worldwide, of which about one-third are resistant to current treatments. Here we report a multi-ancestry genome-wide association study including 29,944 cases, stratified into three broad categories and seven subtypes of epilepsy, and 52,538 controls. We identify 26 genome-wide significant loci, 19 of which are specific to genetic generalized epilepsy (GGE). We implicate 29 likely causal genes underlying these 26 loci. SNP-based heritability analyses show that common variants explain between 39.6% and 90% of genetic risk for GGE and its subtypes. Subtype analysis revealed markedly different genetic architectures between focal and generalized epilepsies. Gene-set analyses of GGE signals implicate synaptic processes in both excitatory and inhibitory neurons in the brain. Prioritized candidate genes overlap with monogenic epilepsy genes and with targets of current antiseizure medications. Finally, we leverage our results to identify alternate drugs with predicted efficacy if repurposed for epilepsy treatment

Genome-wide identification and phenotypic characterization of seizure-associated copy number variations in 741,075 individuals

Copy number variants (CNV) are established risk factors for neurodevelopmental disorders with seizures or epilepsy. With the hypothesis that seizure disorders share genetic risk factors, we pooled CNV data from 10,590 individuals with seizure disorders, 16,109 individuals with clinically validated epilepsy, and 492,324 population controls and identified 25 genome-wide significant loci, 22 of which are novel for seizure disorders, such as deletions at 1p36.33, 1q44, 2p21-p16.3, 3q29, 8p23.3-p23.2, 9p24.3, 10q26.3, 15q11.2, 15q12-q13.1, 16p12.2, 17q21.31, duplications at 2q13, 9q34.3, 16p13.3, 17q12, 19p13.3, 20q13.33, and reciprocal CNVs at 16p11.2, and 22q11.21. Using genetic data from additional 248,751 individuals with 23 neuropsychiatric phenotypes, we explored the pleiotropy of these 25 loci. Finally, in a subset of individuals with epilepsy and detailed clinical data available, we performed phenome-wide association analyses between individual CNVs and clinical annotations categorized through the Human Phenotype Ontology (HPO). For six CNVs, we identified 19 significant associations with specific HPO terms and generated, for all CNVs, phenotype signatures across 17 clinical categories relevant for epileptologists. This is the most comprehensive investigation of CNVs in epilepsy and related seizure disorders, with potential implications for clinical practice

The Effect of Patterned Micro-Structure on the Apparent Contact Angle and Three-Dimensional Contact Line

The measurement of the apparent contact angle on structured surfaces is much more difficult to obtain than on smooth surfaces because the pinning of liquid to the roughness has a tremendous influence on the three phase contact line. The results presented here clearly show an apparent contact angle variation along the three phase contact line. Accordingly, not only one value for the apparent contact angle can be provided, but a contact angle distribution or an interval has to be given to characterize the wetting behavior. For measuring the apparent contact angle distribution on regularly structured surfaces, namely micrometric pillars and grooves, an experimental approach is presented and the results are provided. A short introduction into the manufacturing process of such structured surfaces, which is a combination of Direct LASER Writing (DLW) lithography, electroforming and hot embossing shows the high quality standard of the used surfaces

3D micro-structures for rarefied gas flow applications manufactured via two-photon-polymerization

International audienceIn this work, the two-photon-polymerization (TPP) fabrication technique was employed for the first time to manufacture with success three-dimensional (3D) micro-structures suitable for confined rarefied gas flows. Four different micro-tubes of simple geometry have been tested in vacuum conditions. The geometry of the micro-tubes was characterized via a focus-variation 3D optical measurement microscope, a digital microscope and a X-ray µ-tomography. Mass flow rate measurements of pressure-driven rarefied gas flows of nitrogen in slip and transition regimes are were compared to theoretical values obtained via the kinetic theory of gases. The experimental measurements were realized via the constant volume technique. The good agreement obtained between experimental and numerical results proves the feasibility of using this fabrication technique to create well controlled 3D shaped microsystems for rarefied gas flows applications