Spheroids-on-a-chip: Recent advances and design considerations in microfluidic platforms for spheroid formation and culture

© 2018 Elsevier B.V. A cell spheroid is a three-dimensional (3D) aggregation of cells. Synthetic, in-vitro spheroids provide similar metabolism, proliferation, and species concentration gradients to those found in-vivo. For instance, cancer cell spheroids have been demonstrated to mimic in-vivo tumor microenvironments, and are thus suitable for in-vitro drug screening. The first part of this paper discusses the latest microfluidic designs for spheroid formation and culture, comparing their strategies and efficacy. The most recent microfluidic techniques for spheroid formation utilize emulsion, microwells, U-shaped microstructures, or digital microfluidics. The engineering aspects underpinning spheroid formation in these microfluidic devices are therefore considered. In the second part of this paper, design considerations for microfluidic spheroid formation chips and microfluidic spheroid culture chips (μSFCs and μSCCs) are evaluated with regard to key parameters affecting spheroid formation, including shear stress, spheroid diameter, culture medium delivery and flow rate. This review is intended to benefit the microfluidics community by contributing to improved design and engineering of microfluidic chips capable of forming and/or culturing three-dimensional cell spheroids

Advances on Mechanics, Design Engineering and Manufacturing III

This open access book gathers contributions presented at the International Joint Conference on Mechanics, Design Engineering and Advanced Manufacturing (JCM 2020), held as a web conference on June 2–4, 2020. It reports on cutting-edge topics in product design and manufacturing, such as industrial methods for integrated product and process design; innovative design; and computer-aided design. Further topics covered include virtual simulation and reverse engineering; additive manufacturing; product manufacturing; engineering methods in medicine and education; representation techniques; and nautical, aeronautics and aerospace design and modeling. The book is organized into four main parts, reflecting the focus and primary themes of the conference. The contributions presented here not only provide researchers, engineers and experts in a range of industrial engineering subfields with extensive information to support their daily work; they are also intended to stimulate new research directions, advanced applications of the methods discussed and future interdisciplinary collaborations

Social shaping of digital publishing: exploring the interplay between culture and technology

The processes and forms of electronic publishing have been changing since the advent of the Web. In recent years, the open access movement has been a major driver of scholarly communication, and change is also evident in other fields such as e-government and e-learning. Whilst many changes are driven by technological advances, an altered social reality is also pushing the boundaries of digital publishing. With 23 articles and 10 posters, Elpub 2012 focuses on the social shaping of digital publishing and explores the interplay between culture and technology. This book contains the proceedings of the conference, consisting of 11 accepted full articles and 12 articles accepted as extended abstracts. The articles are presented in groups, and cover the topics: digital scholarship and publishing; special archives; libraries and repositories; digital texts and readings; and future solutions and innovations. Offering an overview of the current situation and exploring the trends of the future, this book will be of interest to all those whose work involves digital publishing

Prediction of drug-drug interaction potential using machine learning approaches

Drug discovery is a long, expensive, and complex, yet crucial process for the benefit of society. Selecting potential drug candidates requires an understanding of how well a compound will perform at its task, and more importantly, how safe the compound will act in patients. A key safety insight is understanding a molecule\u27s potential for drug-drug interactions. The metabolism of many drugs is mediated by members of the cytochrome P450 superfamily, notably, the CYP3A4 enzyme. Inhibition of these enzymes can alter the bioavailability of other drugs, potentially increasing their levels to toxic amounts. Four models were developed to predict CYP3A4 inhibition: logistic regression, random forests, support vector machine, and neural network. Two novel convolutional approaches were explored for data featurization: SMILES string auto-extraction and 2D structure auto-extraction. The logistic regression model achieved an accuracy of 83.2%, the random forests model, 83.4%, the support vector machine model, 81.9%, and the neural network model, 82.3%. Additionally, the model built with SMILE string auto-extraction had an accuracy of 82.3%, and the model with 2D structure auto-extraction, 76.4%. The advantages of the novel featurization methods are their ability to learn relevant features from compound SMILE strings, eliminating feature engineering. The developed methodologies can be extended towards predicting any structure-activity relationship and fitted for other areas of drug discovery and development

Genetic Analysis and Cell Manipulation on Microfluidic Surfaces

Personalized cancer medicine is a cancer care paradigm in which diagnostic and therapeutic strategies are customized for individual patients. Microsystems that are created by Micro-Electro-Mechanical Systems (MEMS) technology and integrate various diagnostic and therapeutic methods on a single chip hold great potential to enable personalized cancer medicine. Toward ultimate realization of such microsystems, this thesis focuses on developing critical functional building blocks that perform genetic variation identification (single-nucleotide polymorphism (SNP) genotyping) and specific, efficient and flexible cell manipulation on microfluidic surfaces. For the identification of genetic variations, we first present a bead-based approach to detect single-base mutations by performing single-base extension (SBE) of SNP specific primers on solid surfaces. Successful genotyping of the SNP on exon 1 of HBB gene demonstrates the potential of the device for simple, rapid, and accurate detection of SNPs. In addition, a multi-step solution-based approach, which integrates SBE with mass-tagged dideoxynucleotides and solid-phase purification of extension products, is also presented. Rapid, accurate and simultaneous detection of 4 loci on a synthetic template demonstrates the capability of multiplex genotyping with reduced consumption of samples and reagents. For cell manipulation, we first present a microfluidic device for cell purification with surface-immobilized aptamers, exploiting the strong temperature dependence of the affinity binding between aptamers and cells. Further, we demonstrate the feasibility of using aptamers to specifically separate target cells from a heterogeneous solution and employing environmental changes to retrieve purified cells. Moreover, spatially specific capture and selective temperature-mediated release of cells on design-specified areas is presented, which demonstrates the ability to establish cell arrays on pre-defined regions and to collect only specifically selected cell groups for downstream analysis. We also investigate tunable microfluidic trapping of cells by exploiting the large compliance of elastomers to create an array of cell-trapping microstructures, whose dimensions can be mechanically modulated by inducing uniform strain via the application of external force. Cell trapping under different strain modulations has been studied, and capture of a predetermined number of cells, from single cells to multiple cells, has been achieved. In addition, to address the lack of aptamers for targets of interest, which is a major hindrance to aptamer-based cell manipulation, we present a microfluidic device for synthetically isolating cell-targeting aptamers from a randomized single-strand DNA (ssDNA) library, integrating cell culturing with affinity selection and amplification of cell-binding ssDNA. Multi-round aptamer isolation on a single chip has also been realized by using pressure-driven flow. Finally, some perspectives on future work are presented, and strategies and notable issues are discussed for further development of MEMS/microfluidics-based devices for personalized cancer medicine