Filtration & fluid control
explains Di Carlo. Another benefit is that reactions can be performed on the particle surface itself, unlike other microfluidics approaches where another component with a surface has to be added to the system. Moreover, with lab-on-a-chip devices, as well as microfluidics more broadly, there is little room to innovate on top of an existing platform: each microfluidic single-cell analysis method has its specific assays and instrumentation. However, Di Carlo says, “In research, everyone is doing something slightly different and they want to do their assay a little bit differently.” Lab-on-a-particle approaches offer this flexibility – and they can usually be done using standard instrumentation found in life science research labs, Di Carlo adds.
Microfluidics enables precise analysis at the cellular level, which is driving advancements in research and the development of therapies.
combining them with the spatial information within the tissue is unbelievably powerful,” says Xavier. He adds that for cancer, it could expand our knowledge on how the disease develops and forms, the tumour microenvironment and metastasis. Researchers are integrating spatial indexing methods with droplet microfluidics to advance high- throughput spatial transcriptomics. This has the potential to uncover disease and developmental trajectories. Meanwhile, there are efforts to replicate this approach for other omics technologies, such as lipidomics or proteomics. Microfluidic channels and droplets can also be made small enough to trap subcellular components. “Now the field is looking into single exosomes and single extracellular vesicles,” says Xavier. As with single-cell analysis, this research aims to analyse small populations of these exosomes and extracellular vesicles, maybe even one at a time.
From lab-on-a-chip to particle-on-a-chip systems
Lab-on-a-chip systems are one of the most translated formats of microfluidics for the analysis of biological samples. Here, as the term suggests, the cells are isolated and analysed in the same device. Cells from a tissue are typically cultured together in what are known as organ-on-a-chip devices. These are highly multiplexable, allowing for rapid screening of a large number of drug candidates. Now, lab-on-a-chip systems are being adapted for single-cell omics analyses. This opens up a host of clinically relevant use cases. For example, hundreds or thousands of antibodies could be simultaneously screened and their impact on cellular processes assessed. Yet some scientists are turning their attention to even finer details. With the lab-on-a-particle approach, “The idea is using a particle, usually a hydrogel, that allows you to put cells or molecules onto it and compartmentalise a reaction so you can measure things very precisely,”
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Single-particle analysis can be achieved with droplet microfluidics or other approaches, as well. However, you would need to shrink the microfluidic channel size from, say, 20-by-20 micrometres to 2-by-2 micrometres. “The technology is there, but it needs to be adapted to the particles you are analysing,” says Xavier.
Manufacturing therapies Microfluidic single-cell analysis could translate into applications spanning oncology, immunology, regenerative medicine and more. It will yield high- throughput insights into disease mechanisms and new biomarkers, thereby accelerating therapy development. However, if they are to be a commercial success, they’ll need to be cheaper to make. Presently, microfluidic chips are made with expensive materials in precision manufacturing facilities. Researchers are investigating designs that use inexpensive materials and more standard manufacturing processes, like 3D printing. But the chip, or whichever microfluidic design traps the cells or particles, is only part of the picture. “People refer to a lab-on-a-chip but it’s more often a chip in the lab,” says Xavier. A range of specialised equipment, such as precision pumps and imaging systems, is required for microfluidic analysis. This makes operating microfluidic devices quite complicated and not very translatable for many labs. “What is missing, and people are working in that direction now, is standardising these devices so that they are compatible with common lab equipment,” says Xavier. Finally, microfluidics could address the growing need to manufacture custom cells. Cell therapies, for example, can treat a range of diseases but manufacturing or performing quality control on them is often exorbitantly expensive. Microfluidics could help scale these efforts. “There could be a nice merger between new medical devices and new microfluidic approaches to perform these analyses,” Di Carlo says. “And lower the costs for cell therapies.” ●
Medical Device Developments /
www.medicaldevice-developments.com
Love Employee/
Shutterstock.com
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