Bio-inspired microfluidics: A review

Abstract

Biomicrofluidics, a subdomain of microfluidics, has been inspired by several ideas from nature. However, while the basic inspiration for the same may be drawn from the living world, the translation of all relevant essential functionalities to an artificially engineered framework does not remain trivial. Here, we review the recent progress in bio-inspired microfluidic systems via harnessing the integration of experimental and simulation tools delving into the interface of engineering and biology. Development of "on-chip" technologies as well as their multifarious applications is subsequently discussed, accompanying the relevant advancements in materials and fabrication technology. Pointers toward new directions in research, including an amalgamated fusion of data-driven modeling (such as artificial intelligence and machine learning) and physics-based paradigm, to come up with a human physiological replica on a synthetic bio-chip with due accounting of personalized features, are suggested. These are likely to facilitate physiologically replicating disease modeling on an artificially engineered biochip as well as advance drug development and screening in an expedited route with the minimization of animal and human trials.

FIG. 1.

An image of a lotus leaf. (a)-(i) Scanning Electron Microscopy (SEM) image of the micropapillae interspersed with nonacosanol tubules on the lotus leaf. Reprinted with permission from W. Barthlott and C. Neinhuis, Planta 202(1), 1–8 (1997). Copyright 1997 Springer Nature. (b) SEM image of a positive replica of a lotus leaf on PDMS. (c) An image of a rose. (c)-(i) SEM image of the microbumps on the rose petal interspersed with nanoscale ridge-like structures. Reprinted with permission from Feng et al., Langmuir 24(8), 4114–4119 (2008). Copyright 2008 Elsevier. (d) SEM image of a rose petal positive replica on PDMS. Reprinted with permission from Ghosh et al., Colloids Surf. A 561(10), 9–17 (2019). Copyright 2019 Elsevier. (e) An image of a pitcher of Nepenthes Alata plant. (e)-(i) SEM image of the pitcher depicting the arrangement of the flaky downward directed lunate cell structures and (e)-(ii) SEM image of the flaky microstructures on the pitcher’s surface. Reprinted with permission from Gaume et al., New Phytol. 156(3), 479–489 (2002). Copyright 2002 John Wiley and Sons.

FIG. 2.

Schematics of the different wetting state models, (a) Young’s model of wetting, (b) Wenzel state of wetting, and (c) Cassie–Baxter’s model of wetting. (d) Schematic of a liquid-infused slippery surface inspired by the pitcher’s surface.

FIG. 3.

(a) Analysis of micromixing through fluorescent microscopy after passing the dye in the stream. Copyright 2012 National Academy of Sciences. (b) Particle image velocimetry analysis of the flow around an air bubble within a microchannel, depicting the whole field velocity vector plot. Reproduced with permission from Wang et al., Exp. Fluids 51(1), 65–74 (2011). Copyright 2010 Springer-Verlag. (c) Deformation of the microchannel wall under flow observed using a confocal microscope. Reproduced with permission from Pang et al., Lab Chip 14(20), 4029–4034 (2014). Copyright 2014 Royal Society of Chemistry. (d) Elongation and the breakup of the droplet within a microchannel captured using a high-speed camera at 10000 frames per second. Reproduced with permission from Arratia et al., Chaos 17(4), 2006–2007 (2007). Copyright 2007 AIP Publishing LLC.

FIG. 4.

(a) Separation of RBCs and cancer cells using the inertial microfluidics and forces acting on them. Reproduced with permission from Hur et al., Lab Chip 11(5), 912 (2011). Copyright 2011 Royal Society of Chemistry. (b) Unique dynamics of RBCs within a microchannel for different shear rates. Reproduced with permission from Dupire et al., Proc. Natl. Acad. Sci. U.S.A. 109(51), 20808 (2012). Copyright 2012 National Academy of Sciences.

FIG. 5.

(a) Schematic showing the fabrication process of the leaf-inspired microreplication process from the natural leaf to fabricating materials. Reprinted with permission from He et al., Adv. Healthc. Mater. 2(8), 1108–1113 (2013). Copyright 2013 John Wiley and Sons. (b) Schematic showing fabrication steps for leaf-mimicking (Pinnate venation-“Hevea brasiliensis” leaf) and the leaf-inspired microfluidic device. Reprinted with permission from Fan et al., RSC Adv. 5(110), 90596–90601 (2015). Copyright 2015 the Royal Society of Chemistry. (c) Optical image of a fabricated microfluidic network within PDMS using palmate venation “Vitis vinifera” leaf as a template for soft lithography process. Reprinted with permission from Priyadarshani et al., in Proceedings of IEEE Sensors (Institute of Electrical and Electronics Engineers Inc., 2018), Vol. 2018, pp. 1–4. Copyright 2018 IEEE. (d) Leaf-inspired microvascular network for deciphering vascular transport process with endothelialized complex network. Reprinted with permission from Miali et al., ACS Appl. Mater. Interfaces 11(35), 31627–31637 (2019). Copyright 2019 the American Chemical Society. (e) Photo of assembled multilayer leaf-inspired microfluidic device (top) and microscopic image of microwell layer covered by leaf venation channel layer (bottom). Reprinted with permission from Mao et al., Biofabrication 10(2), 25008 (2018). Copyright 2018 IOP Publication.

FIG. 6.

Mathematical modeling of flows in biological structures (a) geometrical considerations (b) common mathematical modeling framework.

FIG. 7.

Examples of idealized geometry [(a) aneurysmal blood vessel mimic. (i) Reprinted with permission from Karan et al., Soft Matter 16(24), 5777–5786 (2020). Copyright 2020 the Royal Society of Chemistry. (ii) Reprinted with permission from Bauer et al., Exp. Fluids 60, 1–16 (2019). Copyright 2019 Springer Nature. (c) stenosed blood vessel mimic. (i) Reprinted with permission from Karan et al., Soft Matter 16(24), 5777–5786 (2020). Copyright 2020 the Royal Society of Chemistry. (ii) Reprinted with permission from Wu et al., Int. J. Eng. Sci. (Oxford, U. K.) 147, 103206 (2020). Copyright 2020 Elsevier. (e) Tortuous blood vessel. Reprinted with permission from Vorobtsova et al., Ann. Biomed. Eng. 44, 2228–2239 (2016). Copyright 2020 Springer Nature.] and patient-specific geometry obtained by imaging techniques [(b) aneurysmal blood vessel replica. Reprinted with permission from Taylor et al., Int. J. Num. Meth. Biomed. Eng. 27(7), 1000–1016 (2011). Copyright 2011 John Wiley and Sons. (d) Stenosed blood replica. Reprinted with permission from Azar et al., Comput. Biol. Med. 114, 103436 (2019). Copyright 2019 Elsevier. (f) Tortuous and branched blood vessel replica. Reprinted with permission from Vorobtsova et al., Ann. Biomed. Eng. 44, 2228–2239 (2016). Copyright 2020 Springer Nature.] for studies on flow in vasculature. Subfigures (e) and (f) are for studying the effect of blood vessel tortuosity on coronary hemodynamic [subfigure (f) is obtained using computed tomography angiograms]. In panel (d), the heatmap shows time-averaged wall shear stress.

FIG. 8.

Elements of AI-based modeling.

FIG. 9.

Personalized therapy plan using the convergence of physics and data from a biomimetic microfluidic perspective.