3D-Printed electrochemical sensor-integrated transwell systems
MICROSYSTEMS & NANOENGINEERING
Authors: Rajasekaran, Pradeep Ramiah; Chapin, Ashley Augustiny; Quan, David N.; Herberholz, Jens; Bentley, William E.; Ghodssi, Reza
Abstract
This work presents a 3D-printed, modular, electrochemical sensor-integrated transwell system for monitoring cellular and molecular events in situ without sample extraction or microfluidics-assisted downstream omics. Simple additive manufacturing techniques such as 3D printing, shadow masking, and molding are used to fabricate this modular system, which is autoclavable, biocompatible, and designed to operate following standard operating protocols (SOPs) of cellular biology. Integral to the platform is a flexible porous membrane, which is used as a cell culture substrate similarly to a commercial transwell insert. Multimodal electrochemical sensors fabricated on the membrane allow direct access to cells and their products. A pair of gold electrodes on the top side of the membrane measures impedance over the course of cell attachment and growth, characterized by an exponential decrease (similar to 160% at 10Hz) due to an increase in the double layer capacitance from secreted extracellular matrix (ECM) proteins. Cyclic voltammetry (CV) sensor electrodes, fabricated on the bottom side of the membrane, enable sensing of molecular release at the site of cell culture without the need for downstream fluidics. Real-time detection of ferrocene dimethanol injection across the membrane showed a three order-of-magnitude higher signal at the membrane than in the bulk media after reaching equilibrium. This modular sensor-integrated transwell system allows unprecedented direct, real-time, and noninvasive access to physical and biochemical information, which cannot be obtained in a conventional transwell system. Sensors: Electrochemical measurements of cultured cellsResearchers in the United States have developed a novel system which can measure cellular and molecular events in cell cultures non-invasively and in real-time. The new approach builds on transwell system and is designed to be compatible with existing protocols and tools. The team, led by Reza Ghodssi of the University of Maryland, added electrochemical sensors to the porous membrane normally found in transwell systems, enabling them to measure characteristics of the cultures. An impedance sensor is used to measure cell attachment and growth, while cyclic voltammetry sensors at the bottom measure molecular concentration. The modular platform is 3D printed from autoclavable materials, making the system reusable. With this tool, researchers will have unprecedented access to study the cellular and molecular activity in cell cultures.
Neurodevelopmental effects of prenatal vitamin D in humans: systematic review and meta-analysis
MOLECULAR PSYCHIATRY
Authors: Garcia-Serna, Azahara M.; Morales, Eva
Abstract
Diverse studies have investigated the impact of prenatal exposure to vitamin D levels on brain development; however, evidence in humans has never been systematically reviewed. This article summarized evidence of the association between 25-hydroxyvitamin D [25(OH)D] levels in maternal blood in pregnancy or newborn blood at birth and neurodevelopmental outcomes, including cognition, psychomotor performance, language development, behavioral difficulties, attention deficit and hyperactivity disorder (ADHD), and autistic traits. PubMed, Web of Science and SCOPUS databases were systematically searched for epidemiologic studies published through May 2018 using keywords. Random-effects meta-analyses were conducted. Of 260 identified articles, 25 were included in the present review. Comparing the highest vs. the lowest category of prenatal 25(OH)D levels, the pooled beta coefficients were 0.95 (95% CI -0.03, 1.93;p = 0.05) for cognition, and 0.88 (95% CI -0.18, 1.93;p = 0.10) for psychomotor development. The pooled relative risk for ADHD was 0.72 (95% CI, 0.59, 0.89;p = 0.002), and the pooled odds ratio for autism-related traits was 0.42 (95% CI, 0.25, 0.71;p = 0.001). There was little evidence for protective effects of high prenatal 25(OH)D for language development and behavior difficulties. This meta-analysis provides supporting evidence that increased prenatal exposure to 25(OH)D levels is associated with improved cognitive development and reduced risk of ADHD and autism-related traits later in life. Associations represent a potentially high public health burden given the current prevalence of vitamin D deficiency and insufficiency among childbearing aging and pregnant women.