Controlled viscous fingering in volatile fluid towards spontaneous evolution of ordered 3D patterns.

Mimicking nature using artificial technologies has always been a quest/fascination of scientists and researchers of all eras. This paper characterizes viscous fingering instability-based, lithography-less, spontaneous, and scalable process towards fabrication of 3D patterns like nature-inspired honeycomb structures with ultra-high aspect ratio walls. Rich experimental characterization data on volatile polymer solution evolution in a uniport lifted Hele-Shaw cell (ULHSC) is represented on a non-dimensional phase plot. The plot with five orders of magnitude variation of non-dimensional numbers on each axis demarcates the regions of several newly observed phenomena: 'No retention', 'Bridge breaking', and 'Wall formation' with 'stable' and 'unstable' interface evolution. A new non-dimensional ratio of the velocity of evaporating static interface versus lifting velocity is proposed for the same. This phase plot along with physical insights into the phenomena observed, pave pathways for extending the method to multiport LHSC (MLHSC) to demonstrate multiwell honeycomb structures. The work thus establishes a solid foundation with valuable insights for scalable manufacturing of devices useful for application in biomedical and other domains.

Scalable large-area mesh-structured microfluidic gradient generator for drug testing applications.

Microfluidic concentration gradient generators are useful in drug testing, drug screening, and other cellular applications to avoid manual errors, save time, and labor. However, expensive fabrication techniques make such devices prohibitively costly. Here, in the present work, we developed a microfluidic concentration gradient generator (µCGG) using a recently proposed non-conventional photolithography-less method. In this method, ceramic suspension fluid was shaped into a square mesh by controlling Saffman Taylor instability in a multiport lifted Hele-Shaw cell (MLHSC). Using the shaped ceramic structure as the template, µCGG was prepared by soft lithography. The concentration gradient was characterized and effect of the flow rates was studied using COMSOL simulations. The simulation result was further validated by creating a fluorescein dye (fluorescein isothiocanate) gradient in the fabricated µCGG. To demonstrate the use of this device for drug testing, we created various concentrations of an anticancer drug-curcumin-using the device and determined its inhibitory concentration on cervical cancer cell-line HeLa. We found that the IC50 of curcumin for HeLa matched well with the conventional multi-well drug testing method. This method of µCGG fabrication has multiple advantages over conventional photolithography such as: (i) the channel layout and inlet-outlet arrangements can be changed by simply wiping the ceramic fluid before it solidifies, (ii) it is cost effective, (iii) large area patterning is easily achievable, and (iv) the method is scalable. This technique can be utilized to achieve a broad range of concentration gradient to be used for various biological and non-biological applications.

Bio-Mimicking Brain Vasculature to Investigate the Role of Heterogeneous Shear Stress in Regulating Barrier Integrity.

A continuous, sealed endothelial membrane is essential for the blood-brain barrier (BBB) to protect neurons from toxins present in systemic circulation. Endothelial cells are critical sensors of the capillary environment, where factors like fluid shear stress (FSS) and systemic signaling molecules activate intracellular pathways that either promote or disrupt the BBB. The brain vasculature exhibits complex heterogeneity across the bed, which is challenging to recapitulate in BBB microfluidic models with fixed dimensions and rectangular cross-section microchannels. Here, a Cayley-tree pattern, fabricated using lithography-less, fluid shaping technique in a modified Hele-Shaw cell is used to emulate the brain vasculature in a microfluidic chip. This geometry generates an inherent distribution of heterogeneous FSS, due to smooth variations in branch height and width. hCMEC/D3 endothelial cells cultured in the Cayley-tree designed chip generate a 3D monolayer of brain endothelium with branching hierarchy, enabling the study of the effect of heterogeneous FSS on the brain endothelium. The model is employed to study neuroinflammatory conditions by stimulating the brain endothelium with tumor necrosis factor-α under heterogeneous FSS conditions. The model has immense potential for studies involving drug transport across the BBB, which can be misrepresented in fixed dimension models.

Viscous Fingering in Multiport Hele Shaw Cell for Controlled Shaping of Fluids.

The pursuit of mimicking complex multiscale systems has been a tireless effort with many successes but a daunting task ahead. A new perspective to engineer complex cross-linked meshes and branched/tree-like structures at different scales is presented here. Control over Saffman-Taylor instability which otherwise randomly rearranges viscous fluid in a 'lifted Hele-Shaw cell' is proposed for the same. The proposed control employs multiple-ports or source-holes in this cell, to spontaneously shape a stretched fluid film into a network of well defined webs/meshes and ordered multiscale tree-like patterns. Use of multiple ports enables exercising strong control to fabricate such structures, in a robust and repeated fashion, which otherwise are completely non-characteristic to viscous fingering process. The proposed technique is capable of fabricating spontaneously families of wide variety of structures over micro and very large scale in a period of few seconds. Thus the proposed method forms a solid foundation to new pathways for engineering multiscale structures for several scientific applications including efficient gas exchange, heat transport, tissue engineering, organ-on-chip, and so on. Proposal of multi-port Hele-Shaw cell also opens new avenues for investigation of complex multiple finger interactions resulting in interesting fluid patterns.

Fabrication of Multscale Fractal-Like Structures by Controlling Fluid Interface Instability.

Nature, in quest for the best designs has shaped its vital systems into fractal geometries. Effectual way of spontaneous fabrication of scalable, ordered fractal-like structures by controlling Saffman-Taylor instability in a lifted Hele-Shaw cell is deployed here. In lifted Hele-Shaw cell uncontrolled penetration of low-viscosity fluid into its high-viscosity counterpart is known to develop irregular, non-repeatable, normally short-lived, branched patterns. We propose and characterize experimentally anisotropies in a form of spatially distributed pits on the cell plates to control initiation and further penetration of non-splitting fingers. The proposed control over shielding mechanism yields recipes for fabrication of families of ordered fractal-like patterns of multiple generations. As an example, we demonstrate and characterize fabrication of a Cayley tree fractal-like pattern. The patterns, in addition, are retained permanently by employing UV/thermally curable fluids. The proposed technique thus establishes solid foundation for bio-mimicking natural structures spanning multiple-scales for scientific and engineering use.