Micro-scale technologies propel biology and medicine

Abstract

Historically, technology has been central to new discoveries in biology and progress in medicine. Among various technologies, microtechnologies, in particular, have had a prominent role in the revolution experienced by the life sciences in the last few decades, which will surely continue in the years to come. In this Perspective, we illustrate how microtechnologies, with a focus on microfluidics, have evolved in trends/waves to tackle the boundary of knowledge in the life sciences. We provide illustrative examples of technology-enabled biological breakthroughs and their current and future use in clinics. Finally, we take a closer look at the translational process to understand why the incorporation of new micro-scale technologies in medicine has been comparatively slow so far.

FIG. 1.

Timeline of key life sciences and medical micro-scale technologies and associated milestones. Black: new technologies with arrows pointing to approximate year of first publication and/or release. Blue: important associated events or milestones.

FIG. 2.

Trends in technological development: evolution of publications per year on selected technologies in three application areas: DNA/RNA analysis, protein analysis, and cell analysis comprising organ-on-a-chip devices.

FIG. 3.

Selected technologies for the analysis of oligonucleotides, proteins, and cells: (a) Digital PCR, including droplet digital PCR, micro-well partitioning. and planar imaging of PCR products. Reproduced with permission from Liao and Huang, Micromachines 8(8), 1–7 (2017). Copyright 2017 MDPI. (b) Patterned flow cell molecular principle of next-generation sequencing with Illumina's dye sequencing method,. Adapted with permission from Goodwin et al., Nat. Rev. Genet. 17(6), 333–351 (2016). Copyright 2016 Springer Nature. (c) The zero-mode waveguide nanostructure of single-molecule real-time sequencing with nucleotides being incorporated into the DNA by the bottom-linked polymerase. Reproduced with permission from Eid et al., Science 323(5910), 133–138 (2009). Copyright 2009 The American Association for the Advancement of Science. (d) Protein microarray with 16 368 recombinant proteins and their cellular distribution. Reproduced with permission from Uzoma and Zhu, Genomics Proteomics Bioinforma. 11(1), 18–28 (2013). Copyright 2013 Elsevier. (e) Mass spectrometer with acoustic droplet ejection and electrospray ionization. Adapted with permission from Dirico et al., Med. Chem. Lett. 11, 1101–1110 (2020). Copyright 2020 American Chemical Society. (f) Device with a nanopore to measure resistive pulses from the translocation of individual proteins. Reproduced with permission from Yusko et al., Nat. Nanotechnol. 12(4), 360–367 (2017). Copyright 2017 Springer Nature. (g) The principle of fluorescence-activated cell sorting. (h) Initial steps of single-cell RNA-seq workflow with Drop-seq. Adapted with permission from Macosko et al., Cell 161(5), 1202–1214 (2015). Copyright 2015 Elsevier. (i) 3D-printed and multimaterial cardiac organ-on-a-chip device. Reproduced with permission from Lind et al., Nat. Mater. 16(3), 303–308 (2017). Copyright 2017 Springer Nature.

FIG. 4.

Focus on microfluidic applications: prominent application areas addressed by microfluidics in the life sciences (left) and in clinical research (right). Data are presented for 2020, 2010, and 2000. Node size indicates number of publications that year according to a PubMed search.

FIG. 5.

The translational bottleneck: laboratory-developed technologies must go through technical, regulatory, and commercial transitions before reaching the clinics. A thorough understanding and feedback from the following steps (black dashed line) and the end clinical application (blue dashed line) is critical for success.