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All papers published in this volume have been reviewed through processes administered by the Editors. Reviews were conducted by expert referees to the professional and scientific standards expected of a proceedings journal published by IOP Publishing.• Type of peer review: Double Anonymous• Conference submission management system: ConfTool Pro• Number of submissions received: 24• Number of submissions sent for review: 23• Number of submissions accepted: 21• Acceptance Rate (Submissions Accepted / Submissions Received × 100): 87.5• Average number of reviews per paper: 2• Total number of reviewers involved: 29• Contact person for queries:Name: Manuel GriebEmail: manuel.grieb@tu-dortmund.deAffiliation: TU Dortmund University - Chair of Fluidics

Recent progress in the various lab-on-a-chip microtechnologies is reviewed and the clinical and research areas in which they have made the greatest impact are discussed. Lab-on-a-chip technologies in biomedical research and diagnostics Microfluidics exploits the properties of fluids trapped in submillimetre-scale spaces — the physics behind inkjet printing, DNA microarrays, lab-on-a-chip chemistry and much else — to useful practical effect. In the past decade microfluidic devices have shown considerable promise in diagnostics and primary research in the biological sciences. In this Review, Eric Sackmann, Anna Fulton and David Beebe analyse the progress seen in lab-on-a-chip microtechnologies in recent years and discuss the clinical and research areas in which they have made — and may make — the greatest impact. Microfluidics, a technology characterized by the engineered manipulation of fluids at the submillimetre scale, has shown considerable promise for improving diagnostics and biology research. Certain properties of microfluidic technologies, such as rapid sample processing and the precise control of fluids in an assay, have made them attractive candidates to replace traditional experimental approaches. Here we analyse the progress made by lab-on-a-chip microtechnologies in recent years, and discuss the clinical and research areas in which they have made the greatest impact. We also suggest directions that biologists, engineers and clinicians can take to help this technology live up to its potential.

All papers published in this volume have been reviewed through processes administered by the Editors. Reviews were conducted by expert referees to the professional and scientific standards expected of a proceedings journal published by IOP Publishing Publishing.• Type of peer review: Double Anonymous• Conference submission management system: ConfTool• Number of submissions received: 25• Number of submissions sent for review: 24• Number of submissions accepted: 23• Acceptance Rate (Submissions Accepted / Submissions Received × 100): 92• Average number of reviews per paper: 2• Total number of reviewers involved: 24• Contact person for queries:Name: Manuel GriebEmail: manuel.grieb@tu-dortmund.deAffiliation: TU Dortmund University, Chair of Fluidics

Microfluidic systems are rapidly becoming commonplace tools for high-precision materials synthesis, biochemical sample preparation, and biophysical analysis. Typically, microfluidic systems are constructed in monolithic form by means of microfabrication and, increasingly, by additive techniques. These methods restrict the design and assembly of truly complex systems by placing unnecessary emphasis on complete functional integration of operational elements in a planar environment. Here, we present a solution based on discrete elements that liberates designers to build large-scale microfluidic systems in three dimensions that are modular, diverse, and predictable by simple network analysis techniques. We develop a sample library of standardized components and connectors manufactured using stereolithography. We predict and validate the flow characteristics of these individual components to design and construct a tunable concentration gradient generator with a scalable number of parallel outputs. We show that these systems are rapidly reconfigurable by constructing three variations of a device for generating monodisperse microdroplets in two distinct size regimes and in a high-throughput mode by simple replacement of emulsifier subcircuits. Finally, we demonstrate the capability for active process monitoring by constructing an optical sensing element for detecting water droplets in a fluorocarbon stream and quantifying their size and frequency. By moving away from large-scale integration toward standardized discrete elements, we demonstrate the potential to reduce the practice of designing and assembling complex 3D microfluidic circuits to a methodology comparable to that found in the electronics industry. Significance Microfluidic systems promise to improve the analysis and synthesis of materials, biological or otherwise, by lowering the required volume of fluid samples, offering a tightly controlled fluid-handling environment, and simultaneously integrating various chemical processes. To build these systems, designers depend on microfabrication techniques that restrict them to arranging their designs in two dimensions and completely fabricating their design in a single step. This study introduces modular, reconfigurable components containing fluidic and sensor elements adaptable to many different microfluidic circuits. These elements can be assembled to allow for 3D routing of channels. This assembly approach allows for the application of network analysis techniques like those used in classical electronic circuit design, facilitating the straightforward design of predictable flow systems.

We present the integration of a sample chamber for advanced BioSAXS measurement on the P12 beamline of EMBL Hamburg. The sample chamber is designed to be installed in the beamline P12 at PETRA and BM29 at ESRF with minimal effort to swap the standard sample environment, allowing for a fast and efficient beamline configuration change. The new sample chamber is equipped with an on-axis microscope, including front and back illumination, for sample visualization; an XYZ piezo stage for fine alignment of sample into the beam; an optical port for in situ spectroscopy; and fluidics feedthroughs. This sample environment has been fully integrated on the P12 beamline and employed in users project for scanning SAXS and in vacuum microfluidics applications.

The natural world provides many examples of multiphase transport and reaction processes that have been optimized by evolution. These phenomena take place at multiple length and time scales and typically include gas–liquid–solid interfaces and capillary phenomena in porous media 1 , 2 . Many biological and living systems have evolved to optimize fluidic transport. However, living things are exceptionally complex and very difficult to replicate 3 – 5 , and human-made microfluidic devices (which are typically planar and enclosed) are highly limited for multiphase process engineering 6 – 8 . Here we introduce the concept of cellular fluidics: a platform of unit-cell-based, three-dimensional structures—enabled by emerging 3D printing methods 9 , 10 —for the deterministic control of multiphase flow, transport and reaction processes. We show that flow in these structures can be ‘programmed’ through architected design of cell type, size and relative density. We demonstrate gas–liquid transport processes such as transpiration and absorption, using evaporative cooling and CO 2 capture as examples. We design and demonstrate preferential liquid and gas transport pathways in three-dimensional cellular fluidic devices with capillary-driven and actively pumped liquid flow, and present examples of selective metallization of pre-programmed patterns. Our results show that the design and fabrication of architected cellular materials, coupled with analytical and numerical predictions of steady-state and dynamic behaviour of multiphase interfaces, provide deterministic control of fluidic transport in three dimensions. Cellular fluidics may transform the design space for spatial and temporal control of multiphase transport and reaction processes. Cellular fluidics provides a platform of unit-cell-based, three-dimensional structures for the deterministic control of multiphase flow, transport and reaction processes.

The successes and failures of past research in the development of microfluidic reactors for chemical synthesis are highlighted. Current roadblocks are assessed and a series of challenges for the future of this area are identified. The past two decades have seen far-reaching progress in the development of microfluidic systems for use in the chemical and biological sciences. Here we assess the utility of microfluidic reactor technology as a tool in chemical synthesis in both academic research and industrial applications. We highlight the successes and failures of past research in the field and provide a catalogue of chemistries performed in a microfluidic reactor. We then assess the current roadblocks hindering the widespread use of microfluidic reactors from the perspectives of both synthetic chemistry and industrial application. Finally, we set out seven challenges that we hope will inspire future research in this field.

Microfluidics is a relatively newly emerged field based on the combined principles of physics, chemistry, biology, fluid dynamics, microelectronics, and material science. Various materials can be processed into miniaturized chips containing channels and chambers in the microscale range. A diverse repertoire of methods can be chosen to manufacture such platforms of desired size, shape, and geometry. Whether they are used alone or in combination with other devices, microfluidic chips can be employed in nanoparticle preparation, drug encapsulation, delivery, and targeting, cell analysis, diagnosis, and cell culture. This paper presents microfluidic technology in terms of the available platform materials and fabrication techniques, also focusing on the biomedical applications of these remarkable devices.

The body naturally and continuously secretes sweat for thermoregulation during sedentary and routine activities at rates that can reflect underlying health conditions, including nerve damage, autonomic and metabolic disorders, and chronic stress. However, low secretion rates and evaporation pose challenges for collecting resting thermoregulatory sweat for non-invasive analysis of body physiology. Here we present wearable patches for continuous sweat monitoring at rest, using microfluidics to combat evaporation and enable selective monitoring of secretion rate. We integrate hydrophilic fillers for rapid sweat uptake into the sensing channel, reducing required sweat accumulation time towards real-time measurement. Along with sweat rate sensors, we integrate electrochemical sensors for pH, Cl − , and levodopa monitoring. We demonstrate patch functionality for dynamic sweat analysis related to routine activities, stress events, hypoglycemia-induced sweating, and Parkinson’s disease. By enabling sweat analysis compatible with sedentary, routine, and daily activities, these patches enable continuous, autonomous monitoring of body physiology at rest. Low secretion rates and evaporation pose challenges for collecting resting thermoregulatory sweat for non-invasive analysis of body physiology. Here the authors present wearable microfluidics-based patches for continuous sweat monitoring at rest that enable detection of pH, Cl − , and levodopa for dynamic sweat analysis related to routine activities, stress events, hypoglycemia-induced sweating, and Parkinson’s disease.

Circulating Tumor Cells (CTCs) in blood encompass DNA, RNA, and protein biomarkers, but clinical utility is limited by their rarity. To enable tumor epitope-agnostic interrogation of large blood volumes, we developed a high-throughput microfluidic device, depleting hematopoietic cells through high-flow channels and force-amplifying magnetic lenses. Here, we apply this technology to analyze patient-derived leukapheresis products, interrogating a mean blood volume of 5.83 liters from seven patients with metastatic cancer. High CTC yields (mean 10,057 CTCs per patient; range 100 to 58,125) reveal considerable intra-patient heterogeneity. CTC size varies within patients, with 67% overlapping in diameter with WBCs. Paired single-cell DNA and RNA sequencing identifies subclonal patterns of aneuploidy and distinct signaling pathways within CTCs. In prostate cancers, a subpopulation of small aneuploid cells lacking epithelial markers is enriched for neuroendocrine signatures. Pooling of CNV-confirmed CTCs enables whole exome sequencing with high mutant allele fractions. High-throughput CTC enrichment thus enables cell-based liquid biopsy for comprehensive monitoring of cancer. Circulating tumor cells (CTCs) are clinically useful for detecting and monitoring cancer, but they are rare in blood. Here, the authors use a highthroughput microfluidic device to massively enrich CTCs from leukapheresis products to uncover single cell molecular features in prostate and other cancers.