Prithviraj Mukherjee

Bio: Prithviraj Mukherjee is an academic researcher from University of Illinois at Chicago. The author has contributed to research in topics: Soft lithography & Microfluidics. The author has an hindex of 5, co-authored 6 publications receiving 107 citations. Previous affiliations of Prithviraj Mukherjee include University of Cincinnati.

Label-free microfluidic sorting of microparticles.

Abstract: Massive growth of the microfluidics field has triggered numerous advances in focusing, separating, ordering, concentrating, and mixing of microparticles. Microfluidic systems capable of performing these functions are rapidly finding applications in industrial, environmental, and biomedical fields. Passive and label-free methods are one of the major categories of such systems that have received enormous attention owing to device operational simplicity and low costs. With new platforms continuously being proposed, our aim here is to provide an updated overview of the state of the art for passive label-free microparticle separation, with emphasis on performance and operational conditions. In addition to the now common separation approaches using Newtonian flows, such as deterministic lateral displacement, pinched flow fractionation, cross-flow filtration, hydrodynamic filtration, and inertial microfluidics, we also discuss separation approaches using non-Newtonian, viscoelastic flow. We then highlight the newly emerging approach based on shear-induced diffusion, which enables direct processing of complex samples such as untreated whole blood. Finally, we hope that an improved understanding of label-free passive sorting approaches can lead to sophisticated and useful platforms toward automation in industrial, environmental, and biomedical fields.

Single stream inertial focusing in low aspect-ratio triangular microchannels

Abstract: A wide range of microfluidic devices for single stream focusing of cells and particles has emerged in recent years, based on both passive and active methods. Inertial microfluidics offers an attractive alternative to these methods, providing efficient and sheathless passive focusing of cells and beads. Nevertheless, in rectangular microchannels, the presence of multiple equilibrium positions necessitates complicated solutions involving manipulation of the 3D structure in order to achieve single stream flows. Here, we present a new approach to single-stream inertial focusing based on a triangular microchannel geometry. Changing the channel cross-sectional shape leads to asymmetry in the velocity profile, resulting in a size-dependent single stable equilibrium position near the channel apex. We demonstrate that soft lithography masters for such microchannels can be fabricated using PMMA through micromilling, and 15 μm diameter beads can be efficiently focused into a single stream. Confocal microscopy was used to confirm the focusing positions in the microchannel cross-section. We further integrated this device with a laser counting system to form a sheathless flow cytometer and demonstrated the counting of beads with an ∼326 s -1 throughput. The use of a triangular cross-section offers a number of benefits, including simplicity of the fundamental principle and geometry, control of design, a small footprint, and ease of integration, as well as high-precision single position focusing.

Rapid Prototyping of Soft Lithography Masters for Microfluidic Devices Using Dry Film Photoresist in a Non-Cleanroom Setting.

Abstract: Fabrication of microfluidic devices by soft lithography is by far the most popular approach due to simplicity and low cost. In this approach PDMS (polydimethylsiloxane) is cast on a photoresist master to generate replicas that are then sealed against glass slides using oxygen plasma. In this work, we demonstrated fabrication of soft photolithography masters using lamination of ADEX dry film as an alternative to the now classic SU-8 resist masters formed by spin coating. Advantages of using ADEX dry film include the easily-achievable uniform thickness without edge bead; simplicity of the process with significant time savings due to non-sticky nature of the film; and fewer health concerns due to less toxic developing solution and antimony-free composition. As we demonstrate, the process can be performed in a low-cost improvised fabrication room in ambient light, in place of a conventional yellow-light cleanroom environment. We believe this approach holds the promise of delivering state-of-the-art microfluidic techniques to the broad field of biomedical and pharmaceutical research.

Classification of Hydrogels Based on Their Source: A Review and Application in Stem Cell Regulation

Abstract: Stem cells are recognized by their self-renewal ability and can give rise to specialized progeny. Hydrogels are an established class of biomaterials with the ability to control stem cell fate via mechanotransduction. They can mimic various physiological conditions to influence the fate of stem cells and are an ideal platform to support stem cell regulation. This review article provides a summary of recent advances in the application of different classes of hydrogels based on their source (e.g., natural, synthetic, or hybrid). This classification is important because the chemistry of substrate affects stem cell differentiation and proliferation. Natural and synthetic hydrogels have been widely used in stem cell regulation. Nevertheless, they have limitations that necessitate a new class of material. Hybrid hydrogels obtained by manipulation of the natural and synthetic ones can potentially overcome these limitations and shape the future of research in application of hydrogels in stem cell regulation.

Microfluidic manufacture of rt-PA -loaded echogenic liposomes.

Abstract: Echogenic liposomes (ELIP), loaded with recombinant tissue-type plasminogen activator (rt-PA) and microbubbles that act as cavitation nuclei, are under development for ultrasound-mediated thrombolysis. Conventional manufacturing techniques produce a polydisperse rt-PA-loaded ELIP population with only a small percentage of particles containing microbubbles. Further, a polydisperse population of rt-PA-loaded ELIP has a broadband frequency response with complex bubble dynamics when exposed to pulsed ultrasound. In this work, a microfluidic flow-focusing device was used to generate monodisperse rt-PA-loaded ELIP (μtELIP) loaded with a perfluorocarbon gas. The rt-PA associated with the μtELIP was encapsulated within the lipid shell as well as intercalated within the lipid shell. The μtELIP had a mean diameter of 5 μm, a resonance frequency of 2.2 MHz, and were found to be stable for at least 30 min in 0.5 % bovine serum albumin. Additionally, 35 % of μtELIP particles were estimated to contain microbubbles, an order of magnitude higher than that reported previously for batch-produced rt-PA-loaded ELIP. These findings emphasize the advantages offered by microfluidic techniques for improving the encapsulation efficiency of both rt-PA and perflurocarbon microbubbles within echogenic liposomes.

Beyond pdms: : off-stochiometry thiol-ene based soft lithography for rapid prototyping of microfluidic devices

Abstract: We present an easy to use, rapid fabrication platform for microfluidic systems, based on micro-molding of novel thiolene based polymer formulations. The novel fabrication platform addresses major d ...

Continuous Separation of Microparticles in a Microfluidic Channel via the Elasto-inertial Effect of Non-Newtonian Fluid

Abstract: Pure separation and sorting of microparticles from complex fluids are essential for biochemical analyses and clinical diagnostics. However, conventional techniques require highly complex and expensive labeling processes for high purity separation. In this study, we present a simple and label-free method for separating microparticles with high purity using the elasto-inertial characteristic of a non-Newtonian fluid in microchannel flow. At the inlet, particle-containing sample flow was pushed toward the side walls by introducing sheath fluid from the center inlet. Particles of 1 μm and 5 μm in diameter, which were suspended in viscoelastic fluid, were successfully separated in the outlet channels: larger particles were notably focused on the centerline of the channel at the outlet, while smaller particles continued flowing along the side walls with minimal lateral migration towards the centerline. The same technique was further applied to separate platelets from diluted whole blood. Through cytometric analysis, we obtained a purity of collected platelets of close to 99.9%. Conclusively, our microparticle separation technique using elasto-inertial forces in non-Newtonian fluid is an effective method for separating and collecting microparticles on the basis of size differences with high purity.

3D Printing of Inertial Microfluidic Devices.

Abstract: Inertial microfluidics has been broadly investigated, resulting in the development of various applications, mainly for particle or cell separation. Lateral migrations of these particles within a microchannel strictly depend on the channel design and its cross-section. Nonetheless, the fabrication of these microchannels is a continuous challenging issue for the microfluidic community, where the most studied channel cross-sections are limited to only rectangular and more recently trapezoidal microchannels. As a result, a huge amount of potential remains intact for other geometries with cross-sections difficult to fabricate with standard microfabrication techniques. In this study, by leveraging on benefits of additive manufacturing, we have proposed a new method for the fabrication of inertial microfluidic devices. In our proposed workflow, parts are first printed via a high-resolution DLP/SLA 3D printer and then bonded to a transparent PMMA sheet using a double-coated pressure-sensitive adhesive tape. Using this method, we have fabricated and tested a plethora of existing inertial microfluidic devices, whether in a single or multiplexed manner, such as straight, spiral, serpentine, curvilinear, and contraction-expansion arrays. Our characterizations using both particles and cells revealed that the produced chips could withstand a pressure up to 150 psi with minimum interference of the tape to the total functionality of the device and viability of cells. As a showcase of the versatility of our method, we have proposed a new spiral microchannel with right-angled triangular cross-section which is technically impossible to fabricate using the standard lithography. We are of the opinion that the method proposed in this study will open the door for more complex geometries with the bespoke passive internal flow. Furthermore, the proposed fabrication workflow can be adopted at the production level, enabling large-scale manufacturing of inertial microfluidic devices.

Channel innovations for inertial microfluidics

Abstract: Inertial microfluidics has gained significant attention since first being proposed in 2007 owing to the advantages of simplicity, high throughput, precise manipulation, and freedom from an external field. Superior performance in particle focusing, filtering, concentrating, and separating has been demonstrated. As a passive technology, inertial microfluidics technology relies on the unconventional use of fluid inertia in an intermediate Reynolds number range to induce inertial migration and secondary flow, which depend directly on the channel structure, leading to particle migration to the lateral equilibrium position or trapping in a specific cavity. With the advances in micromachining technology, many channel structures have been designed and fabricated in the past decade to explore the fundamentals and applications of inertial microfluidics. However, the channel innovations for inertial microfluidics have not been discussed comprehensively. In this review, the inertial particle manipulations and underlying physics in conventional channels, including straight, spiral, sinusoidal, and expansion-contraction channels, are briefly described. Then, recent innovations in channel structure for inertial microfluidics, especially channel pattern modification and unconventional cross-sectional shape, are reviewed. Finally, the prospects for future channel innovations in inertial microfluidic chips are also discussed. The purpose of this review is to provide guidance for the continued study of innovative channel designs to improve further the accuracy and throughput of inertial microfluidics.

Viscoelastic microfluidics: progress and challenges.

Abstract: The manipulation of cells and particles suspended in viscoelastic fluids in microchannels has drawn increasing attention, in part due to the ability for single-stream three-dimensional focusing in simple channel geometries. Improvement in the understanding of non-Newtonian effects on particle dynamics has led to expanding exploration of focusing and sorting particles and cells using viscoelastic microfluidics. Multiple factors, such as the driving forces arising from fluid elasticity and inertia, the effect of fluid rheology, the physical properties of particles and cells, and channel geometry, actively interact and compete together to govern the intricate migration behavior of particles and cells in microchannels. Here, we review the viscoelastic fluid physics and the hydrodynamic forces in such flows and identify three pairs of competing forces/effects that collectively govern viscoelastic migration. We discuss migration dynamics, focusing positions, numerical simulations, and recent progress in viscoelastic microfluidic applications as well as the remaining challenges. Finally, we hope that an improved understanding of viscoelastic flows in microfluidics can lead to increased sophistication of microfluidic platforms in clinical diagnostics and biomedical research. Insights into the dynamic behavior of biological fluids on the microscale are enabling more efficient analysis of cells, bacteria, and other small biological particles for research and clinical diagnostics. Blood, saliva and other biofluids have viscoelastic properties, which means that they exhibit both viscous and elastic behaviors depending on the forces to which they are subjected. These properties shape the migration behaviors of suspended bioparticles in unique ways. Jian Zhou and Ian Papautsky of the University of Illinois at Chicago have reviewed current progress in understanding the migration behaviors in such fluids within microfluidic devices. The authors discuss design principles that have enabled the development of microfluidic systems capable of separating and purifying cells, bacteria, and small vesicles from highly heterogeneous biological specimens, and highlight future challenges that need to be addressed.