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Scalable Fabrication Of Bio Inspired 3 D Micro/Nanofludic Devices

Abstract: ABSTRACT A bio-inspired 3D-micro/nanofluidic device manufacture by a scalable fabrication process, wherein the device comprises either a thin micro/nanovascularized membrane matrices or Polydimethylsiloxane (PDMS) or dimethicone membranes interfaced with fractal microchannel networks in polymers mimicking secondary lamella of fishes or , fractal-shaped microchannel network connected to interconnected micro/nanoporous structure similar to the plant leaves for achieving enhanced fluid-flow and mass transfer capabilities. Thin micro/nanovascularized membrane matrices are made of Polydimethylsiloxane (PDMS) or dimethicone membranes. A method for fabricating a secondary lamella inspired 3D-micro/nanofluidic device for heat and mass transfer comprising the following method steps: fabricating the fractal mold; depositing random micro/nanofibers; pouring PDMS in a predetermined ratio; removing the mold with open fractal micro-channels connected with micro/nanofibers duly embedded in PDMS matrix; submerging the PDMS matrix in DMF solvent and allowing the fibers to be etched away; and closing thin PDMS matrix with open channels by bonding with PDMS membrane. The method of fabricating leaf inspired micropump comprises following steps: fabrication of fractal mold in HDDA, pouring PDMS in a predetermined ratio, removing the PDMS mold with fractal-shaped microchannels, bonding the open-end of fractal-shaped channels in PDMS with micro/nanoporous substrate by an intermediate partially cured thin PDMS membranes. Thus, invention describes two scalable manufacturing process for design and fabrication to types of bio-inspired 3D microfluidic device; 1) micro/nanovascularised membrane based microfluidic device for gas/solute separation b) passive micropump for fluid pumping. FIGURE 2 FIGURE 24

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Patent Information

Application #
Filing Date
28 April 2017
Publication Number
44/2018
Publication Type
INA
Invention Field
POLYMER TECHNOLOGY
Status
Email
patent@royzz.com
Parent Application

Applicants

IITB-Monash Research Academy
IIT Bombay Powai Mumbai

Inventors

1. Prasoon Kumar
Department : Mechanical IIT Bombay Powai Mumbai - 400076
2. Prasanna S.Gandhi
Department : Mechanical IIT Bombay Powai Mumbai - 400076
3. Mainak Majumder
Department : Mechanical and Aerospace Engineering Monash University Clayton

Specification

FORM-2 THE PATENTS ACT, 1970 (39 Of 1970) & THE PATENTS RULES, 2003 COMPLETE SPECIFICATION (See section 10 and rule 13) Title: SCALABLE FABRICATION OF BIO-INSPIRED 3D-MICRO/NANOFLUIDIC DEVICES Applicant: IITB Monash Research Academy NT Bombay Powai Mumbai 400 076 Inventors Prasoon Kumar Prasanna S. Gandhi Mainak Majumdar THE FOLLOWING SPECIFICATION PARTICULARLY DESCRIBES THE INVENTION AND THE MANNER IN WHICH IT IS TO BE PERFORMED. FIELD OF INVENTION The present invention relates to design and scalable fabrication of bio-inspired vasculature in polymer matrices to be used in micro/nanofluidic devices. In particular, the present invention relates to bio-inspired, 3D-micro/nanofluidic devices having such micro/nanovascularized polymer matrices to mimic natural vascular pattern of living organisms, where fractal micro-channels are connected to random network of nanochannels. More particularly, the present invention relates to leaf inspired micropumps made by using scalable micro-technologies, with fractal micro-channels are connected to microporous substrate. The invention also relates to the method of manufacturing micro/nanovascularized polymer membrane matrices with fractal micro-channels and bio-inspired 3D-micro/nanofluidic devices made therefrom as well as leaf inspired micropumps made by using scalable micro-technologies. BACKGROUND OF THE INVENTION Biomimicry is the approach to seek innovative and sustainable solutions to complex human problems by emulating nature's time-tested patterns and strategies. The object of the biomimicry is to develop products, processes, and strategies or new ways of living. This is because; all the Hiving organisms have evolved into well-adapted structures and materials on our planet over millions of years through the process of natural selection. The basic idea underlying biomimicry or biomimetics is to adapt the solutions to many problems which are already solved by nature. In fact, animals, plants, and microbes are the consummate engineers. So, fossils are the only failures after billions of years of research and development by nature. However, there is plenty of evidence surrounding us, which provides a glimpse into the secret to survival. PRIOR ART US 8951302 B2 entitled Biomimetic vascular network and devices using the same discloses a method of fabricating a scaffold comprising a fluidic network, including the steps of: (a) generating an initial vascular layer for enclosing the chamber and providing fluid to the cells, the initial vascular layer having a network of channels for fluid; (b) translating the initial vascular layer into a model for fluid dynamics analysis; (c) analyzing the initial vascular layer based on desired parameters selected from the group consisting of a characteristic of a specific fluid, an input pressure, an output pressure, an overall flow rate and combinations thereof to determine sheer stress and velocity within the network of channels; (d) measuring the sheer stress and the velocity and comparing the obtained values to predetermined values;; (e) determining if either of the shear stress or the velocity are greater than or less than the predetermined values, and (f) optionally modifying the initial vascular layer and repeating steps (b)-(e). The invention also provides compositions comprising a vascular layer for use in tissue lamina as well as medical devices having a vascular layer and kits. US 8409502 B2 entitled Methods, apparatuses, and applications for compliant membrane blood gas exchangers discloses a compliant blood gas exchanger including a housing having a first end cap, a second end cap, and an elastomeric sidewall or sleeve extending there between forming a chamber. A hollow fiber assembly is disposed in the chamber. The hollow fiber assembly has a first mounting collar, a second mounting collar and a plurality of hollow fibers disposed there between. The first end cap is disposed in communication with the first mounting collar and the second end cap is disposed in communication with the second mounting collar. The end caps are connected to a gas inlet and a gas outlet. The chamber is in communication with a blood inlet and a blood outlet. The elastomeric sidewall is responsive to internal and external pressures affecting the chamber. The first chamber can also be placed adjacent to a second chamber and both chambers placed within a rigid outer housing.; Thus, a dual-chamber pulsatile blood gas exchanger can be provided. That is, the second chamber may be in connection with a pump mechanism or vacuum mechanism such that the chamber creates a pulsatile flow within the first chamber. US 8252094 B2 entitled Gas exchange membrane in particular for use in an artificial lung and method for the production of a gas exchange membrane of this type discloses a gas exchange membrane is for use in an artificial lung. The membrane consists of a foamed, closed-cell material, in particular of silicone rubber. The membrane is produced by extruding a basic material containing a foaming agent. The extrudate is then foamed. This results in gas exchange membrane having increased gas exchange performance compared to known material due to high permeability of the surface. US 7763097 B2 entitled Devices, systems and methods for reducing the concentration of a chemical entity in fluids discloses a device for removal of at least a portion of carbon dioxide from an aqueous fluid includes at least one membrane through which carbon dioxide can pass to be removed from the fluid and immobilized carbonic anhydrase on or in the vicinity of a first surface of the membrane to be contacted with the fluid such that the immobilized carbonic anhydrase comes into contact with the fluid. The first surface exhibits carbonic anhydrase activity of at least 20% of maximum theoretical activity of the first surface of the membrane based on monolayer surface coverage of carbonic anhydrase if the carbonic anhydrase is immobilized on the first surface. US 6723132 B2 entitled Artificial lung device discloses an artificial lung for humans and other mammals inserted within the body or placed externally. The artificial lung comprises an electrically actuated three-way valve, a casing containing parallel loops of oxygenator tubes for oxygenation of blood by an atmosphere of circulating air, and an air circulation driving fan powered by an energizing system. As a safety factor in the event of leakage in the casing, a check valve is inserted in an effluent blood duct from the casing to the aerated effluent blood. Two artificial lungs can be utilized internally as left and right lungs. US 20110270412 A1 entitled Fabrication of a vascular system using sacrificial structures discloses a method of producing a vascular network preform (VNP). This method involves forming a network of elongate fibers and at least one elongate structure from a sacrificial material. The diameter of the elongate structure is greater than that of the elongate fibers. The network of elongate fibers is placed in contact with at least one elongate structure either following or during forming the network of elongate fibers or forming the at least one elongate structure. A matrix is applied around the network of elongate fibers, in contact with the at least one elongate structure. The network of elongate fibers and elongate structure, within the matrix is sacrificed to form a preform.; The resulting preform contains a vascular network of fine diameter tubes in contact with at least one elongate passage having a diameter greater than that of the fine diameter tubes. The resulting solid preform and methods of using it are also disclosed. NON-PATENT LITERATURE: NP1) Esser-Kahn A P, Thakre P R, Dong H, Patrick J F, Vlasko-Vlasov V K, Sottos N R, Moore J S and White S R 2011 Three-Dimensional Microvascular Fiber-Reinforced Composites. Advanced Materials. 23 3654-58. This article concerns a method for fabricating microvascular networks in fiber-reinforced composites is presented. The method relies on sacrificial fibers woven into fiber preforms that, when removed by depolymerization and volatilization, create 3D microvascular networks inside the composite material. By circulation of functional liquids in the resulting channels, a diverse set of new functionality is demonstrated. Simplicity, robustness, scalability, and reliance on readily available components make this method compatible with composite manufacturing methods. NP2) Huang J-H, Kim J, Agrawal N, Sudarsan A P, Maxim J E, Jayaraman A and Ugaz V M 2009 Rapid Fabrication of Bio-inspired 3D Microfluidic Vascular Networks. Advanced Materials. 21 3567-71. This article discusses a new method to embed branched 3D microvascular fluidic networks inside plastic substrates by harnessing electrostatic discharge phenomena is introduced. This nearly instantaneous process reproducibly generates highly branched tree-like microchannel architectures that bear remarkable similarity to naturally occurring vasculature. This method can be applied to a variety of polymers, and may help enable production of organ-sized tissue scaffolds containing embedded vasculature. NP3) Leon M. Bellan E A S, and Harold G. Craighead 2008 Nanochannels fabricated in poiydimethyisiloxane using sacrificial electrospun polyethylene oxide nanofibers. Journal of Vacuum Science & Technology. 26, 1728. Here, the authors have used electrospun polyethylene oxide nanofibers as sacrificial templates to form nanofluidic channels in poiydimethyisiloxane (PDMS). By depositing fibers on silicon templates incorporating larger structures, the authors demonstrate that these nanochannels can be integrated easily with microfluidics. Fluorescence microscopy was used to image channels filled with dye solution. The utility of the hybrid micro- and nanofluidic PDMS structures for single molecule observation and manipulation was demonstrated by introducing single molecules of A-DNAA-DNA into the channels. This nanofabrication technique allows only a simple construction of nanofluidic PDMS structures without lithographic nanofabrication techniques. NP4) Gualandi C, Zucchelli A, Fernandez Osorio M, Belcari J and Focarete M L 2013 Nanovascularization of Polymer Matrix: Generation of Nanochannels and Nanotubes by Sacrificial Electrospun fibers. Nano Letters. 13 5385-90. This article discusses several methods developed for creating vascular structures, made of either discrete or interconnected channels. The currently employed methods enable the formation of channels with diameters in the millimetric and micrometric scale. However, the formation of an interconnected three-dimensional (3D) vasculature by using a rapid and scalable process is a challenge and largely limits the fields of applicability of these innovative materials. Here, it is proposed to use electrospun nonwoven mats as sacrificial fibers to easily generate 3D macroscale vascularized composites containing interconnected networks with channels and tubes having submicrometric and nanometric diameters. The novel approach has the potentialities to give rise to a novel generation of composites potentially displaying new and enhanced functionalities thanks to the nanoscale features of the cavities. NP5) Bellan L M, Singh S P, Henderson P W, Porri T J, Craighead H G and Spector J A 2009 Fabrication of an artificial 3-dimensional vascular network using sacrificial sugar structures. Soft Matter. 5 13547. This paper discusses forming a 3D fluidic vascular network in a polymeric matrix by using sacrificial sugar structures. Melt-spun sugar fibers (cotton candy) were used to form channels with diameters and densities similar to those of capillaries. To interface to macroscopic fluidic systems, larger sacrificial sugar structures were used to form an artificial inlet and outlet. To verify that the channel network supported flow, they have used video fluorescence microscopy to image both 2 urn fluorescent polystyrene spheres in an aqueous solution and fluorescently labeled blood. This fabrication process may be applied to a wide range of polymeric materials and is rapid, inexpensive, and highly scalable. NP6) Bellan L M, Pearsall M, Cropek D and Langer R 2012 A 3D interconnected microchannel network formed in gelatin by sacrificial shellac microfibers. Advanced materials. (Deerfield Beach, Fla.) 24 5187-91. This paper discusses fabricating 3D microfluidic networks are fabricated in a gelatin hydrogel using sacrificial melt-spun microfibers made from a material with pH-dependent solubility. The fibers, after being embedded within the gel, can be removed by changing the gel pH to induce dissolution. This process is performed in an entirely aqueous environment, avoiding extreme temperatures, low pressures, and toxic organic solvents. NP7) Joseph A. Potkay The promise of microfluidic artificial lungs. Lab on chip. RSC 2014 14, 4122-38. This paper reviews recent research efforts in microfluidic artificial lungs targeted at achieving the advantages above, investigates the ultimate performance and scaling limits of these devices using a proven mathematical model, and discusses the future challenges that must be overcome in order for microfluidic artificial lungs to be applied in the clinic. If all of these promising advantages are realized and the remaining challenges are met, microfluidic artificial lungs could revolutionize the field of pulmonary rehabilitation. NP8) K. M. Kovach et al In vitro evaluation and in vivo demonstration of a biomimetic, hemocompatible, microfluidic artificial lung. Lab on chip. 2015,15, 1366- 1375. This article discusses the first microfluidic artificial lung featuring a hemocompatible surface coating and a biomimetic blood path. The polyethylene-glycol (PEG) coated microfluidic lung exhibited a significantly improved in vitro lifetime compared to uncoated controls as well as consistent and significantly improved gas exchange over the entire testing period. Enabled by their hemocompatible PEG coating, they additionally describe the first extended (3 h) in vivo demonstration of a microfluidic artificial lung. NP9) Kim S, Heller J, Iqbal Z, Kant R, Kim EJ, Durack J, Saeed M, Do L, Hetts S, Wilson M, Brakeman P, Fissell WH, Roy S. Preliminary Diffusive Clearance of Silicon Nanopore Membranes in a Parallel Plate Configuration for Renal Replacement Therapy. ASAIO J. 2016. Mar-Apr; 62(2):169-75. PMID: 26692401. This paper present an initial evaluation of the Silicon Nanopore Membranes (SNM)'s mechanical robustness, diffusive clearance, and hemocompatibility in a parallel plate configuration. The authors have conducted mechanical robustness of the SNM, performed diffusive clearance, evaluated the hemocompatibility, measured the pressure drop across the flow cell. The mechanical testing was done to check the capability of SNM to withstand the pressure without any fracture. Urea clearance was also carried out for measuring blood versus albumin solution. Extracorporeal studies have also shown blood was successfully driven via the arterial-venous pressure differential without thrombus formation. Bare silicon showed increased cell adhesion with a 4.1-fold increase and 1.8-fold increase over polyethylene glycol (PEG)-coated surfaces for tissue plasminogen factor (t-PA) and platelet adhesion (CD41), respectively. All these initial results can be used for further design and development of a full-scale SNM-based parallel plate dialyzerfor renal replacement therapy. NP10) Kensinger C, Karp S, Kant R, Chui BW, Goldman K, Yeager T, Gould ER, Buck A, Laneve DC, Groszek JJ.Roy S, Fissell WH. First Implantation of Silicon Nanopore Membrane Hemofilters. ASAIO J. 2016 Jul-Aug; 62(4):491-495. PMID: 26978710. This paper discusses an implantable hemofilter for the treatment of kidney failure depends critically on the transport characteristics of the membrane and the biocompatibility of the membrane, cartridge, and blood conduits. A novel membrane with slit-shaped pores optimizes the trade-off between permeability and selectivity, enabling implanted therapy. Sustained (3-8) day function of an implanted parallel-plate hemofilter with minimal anticoagulation was achieved by considering biocompatibility at the subnanometer scale of chemical interactions and the millimeter scale of blood fluid dynamics. Therefore, a detailed mechanistic and materials science attention to blood-material interactions allows implanted hemofilters to resist thrombosis. It suggests additional testing to determine optimal membrane characteristics and identify limiting factors in long-term implantation. NP11) Kim S, Feinberg B, Kant R, Chui B, Goldman K, Park J, Moses W, Blaha C, Iqbal Z, Chow C, Wright N, Fissell WH, Zydney A, Roy S. Diffusive Silicon Nanopore Membranes for Hemodialysis Applications. PLoS One. 2016; 11(7): e0159526. PMID: 27438878. This article proposes a fundamentally different approach using microelectromechanical systems (MEMS) fabrication techniques to create thin-flat sheets of silicon-based membranes for implantable or portable hemodialysis applications. The silicon nanopore membranes (SNM) have biomimetic slit-pore geometry and uniform pores size distribution that allow for exceptional permeability and selectivity. A quantitative diffusion model identified structural limits to diffusive solute transport and motivated a new microfabrication technique to create SNM with enhanced diffusive transport. In vitro testing and extracorporeal testing was performed in pigs on prototype membranes with an effective surface area of 2.52 cm2 and 2.02 cm2, respectively. The diffusive clearance was a two-fold improvement in with the new microfabrication technique and was consistent with our mathematical model. These results establish the feasibility of using SNM for hemodialysis applications with additional scale-up. NP12) Jing-min Li, Chong Liu, Zheng Xu, Kai-ping Zhang, Xue Ke, Chun-yu Li and Li-ding Wang, A bio-inspired micropump based on stomatal transpiration in plants. Lab Chip 2011, 11, 2785-89. This article discusses that stomatal transpiration is an efficient way to carry water from the roots up to the leaves, and is described by "diameter-law", which says: the flow rate induced by micropore transpiration far exceeded that induced by macroscale evaporation, and it can be controlled by opening (or closing) some micropores. Accordingly, a bio-inspired micropump based on stomatal transpiration is made. This micropump is composed of three layers: the top layer is a 93 urn-thick PVC (polyvinylchloride) film with a group of slit-like micropores; the second layer is a PMMA sheet with adhesives to join the other two layers together; the third layer is a microporous membrane. By using this pump, controllable flow rates can be obtained. This micropump features high and adjustable flow-rates, simple structure and low fabrication cost, thus it can be used as a "plug and play" fluid-driven unit without any external power sources and equipment. NP13) Li Jingmin, Liu Chong, Xu Zheng 1, Zhang Kaiping, Ke Xue, Wang Liding, A Microfluidic Pump/Valve Inspired by Xylem Embolism and Transpiration in Plants. PLOS ONE. Volume 7, Issue 11,e50320. This article present the design of a biomimetic microfluidic pump/valve based on water transpiration and xylem embolism. This micropump/valve is mainly composed of three parts: the first is a silicon sheet with an array of slit-like micropores to mimic the stomata in a plant leaf; the second is a piece of agarose gel to mimic the mesophyll cells in the sub-cavities of a stoma; the third is a micro-heater which is used to mimic the xylem embolism and its self-repairing. The solution in the microchannels of a microfluidic chip can be driven by the biomimetic "leaf" composed of the silicon sheet and the agarose gel. The halting and flowing of the solution is controlled by the micro-heater. This micropump/valve can also be used as a "plug and play" fluid-driven unit. NP14) Robert Crawford, Thomas E. Murphy, Alexandre K. da Silva, Halil Berberoglu, Experimental characterization of the effects of geometric parameters on evaporative pumping. Experimental Thermal and Fluid Science 51 (2013) 183-188. This paper presents a for determining the experimental relation between the suction pressure and evaporation rate from the upper surface of a flat, thin porous membrane, which naturally draws water from a reservoir, and its microchannel feeding system. The effects of three main design parameters of a water delivery system on the evaporation rate of the membrane are considered: which are (i) the diameter of the microchannels irrigating the membrane, (ii) the length of the irrigating microchannels, and (iii) the surface area of the membrane. Also, an evaluation about the effect of the pumping height on the evaporation rates for the three design parameters was done. While the maximum evaporation rate from the membrane is a function of the membrane's properties like permeability and porosity, as well as the ambient conditions like temperature, pressure and humidity; the geometric parameters of closed water-feeding microchannels that properly hydrate a porous membrane while not impeding evaporation were determined. The results confirm that the evaporation rate was mostly unaffected by the channel dimensions considered and the evaporation rates increased with increasing surface area but at decreasing rate of return. Finally, suction pressures achieved were inversely related to hydrodynamic pressure drop and thus unaffected by the membrane diameter. All above patent and non-patent literature encourages the present inventors to study the natural phenomenon of chemical species separation under convective diffusive flow present in fish gill, which facilitates a critical function in the respiratory and excretory functions of fish by using primary and secondary lamella therein. Since the secondary lamella of fish gills is aggregate of epithelial cells in an extracellular matrix having fractal capillaries and micro capillaries, the entire structure of secondary lamella could be compared to a vascularized polymer membrane matrices, which find applications in various domain like tissue engineering, drug delivery, self-healing and self-cooling materials and micro/nanofluidic devices used in artificial organs. For such applications, it was preferred by the researchers to design and fabricate vascularized polymer matrices by various methods like vaporization of sacrificial structures, sacrificial etching by solvents, electric discharge, ghost ink 3D printing etc. There were previous attempts at biomimicry of vascular network in polymer matrices through various micro-technologies; however, these did not result in a successful design of multi-scale vascular network until now. Moreover, previous lithography based micro-technologies suffer from non-scalability, high cost of operation and investment on equipment and material compatibility while non-lithography based techniques experienced challenges like interfacing of nanofluidic networks with microfluidic channels and fabrication of bio-inspired, 3D, multi-scale nature of channel networks . To achieve the above object and for establishing an efficient connection of nanovascularized polymer matrices, there is a need for designing, fabricating and characterizing micro/nanovascularized polymer matrices, which have fractal micro-channels connected to random network of nanochannels and utilizing them for developing 3D micro/nanofluidic devices that can be used for separation of small molecules useful in chemical and biomedical industries. Further, there is a requirement of design, fabrication, characterization and application thereof of a system where fractal micro-channels can also be integrated with micro/nanoporous substrates to generate leaf inspired micropumps that exhibit enhanced volumetric pumping of water and pressure head sustenance, desirable in applications like passive fluid pumping in lab-on-chip devices, development of solar distillation plants, designing ways for microelectronic circuit cooling, advanced drug delivery etc. DISADVANTAGES WITH THE PRIOR ART However, the problem with the conventional devices and methods proposed in the prior art is either not scalable or limited by fine control over the dimensions of vascular channels. In addition, there is a limited control over the volume of fluid dispensed through the matrices. The direct connection of vascularized polymer matrices or porous substrate with tubing, connected to an external fluidic port leads to low volume of fluid dispensed through vascularized polymer matrices or porous substrate. Moreover, if the dimensions of vascular channels or pores in the polymer matrices are reduced further to a nanometer dimension, the above method of tubing would lead to an even lower volume of fluid through nanovascularized polymer matrices. This would also lead to an underutilization of available surface area of nano/microvascularized polymer matrices for any applications. Therefore, it is the object of the invention to design and develop vascularized polymer matrices membranes or micro/nanoporous substrates interfaced with the fractal pattern of micro-channels mimicking natural vascular pattern of living organisms. This would facilitate an efficient delivery of fluid through fractal channels connected to random network of micro/nanochannels or micro/nanoporous substrates and thus a better exchange of gases/solute across the membrane matrices through nanovascularized regions and pumping of fluid by micro/nanoporous substrate experiencing transpiration. OBJECTS OF THE INVENTION Some of the objects of the present invention - satisfied by at least one embodiment of the present invention - are as follows: An object of the present invention is to develop and manufacture bio-inspired 3D-micro/nanofluidic devices having the fractal pattern of microchannels to mimic natural vascular pattern of living organisms, e.g. inspired from the structural parameters of fish gills and their role in gas/solute exchange or leaves of plants. Another object of the present invention is to develop and manufacture bio-inspired 3D-micro/nanofluidic devices by means of scalable fabrication process and useful for applications demanding heat and mass transfer under convective flow process. Still another object of the present invention is to develop and manufacture thin micro/nanovascularized PDMS matrices based 3D devices which have enhanced fluid-flow and mass-transfer capabilities. Yet another object of the present invention is to develop and manufacture leaf inspired micropumps, which demonstrate enhanced passive pumping and sustaining pressure head and achieve high volume of fluid pumping with external power source. Another object of the present invention is to develop a scalable method for integration of micro/nanoporous, fibrous/non-fibrous substrate with fractal-shaped 3D microchannels for efficient delivery of fluid to micro/nanoporous substrate. Yet another object of the present invention is to develop a manufacturing method for interfacing of micro/nanoporous, fibrous/non-fibrous substrate with fractal-shaped 3D microchannels for effective utilization of available surface area of micro/nanoporous substrate during transpiration assisted capillary pumping of fluid. A further object of the present invention is to develop and fabricate micro/nanovascularized polymer membrane matrices, which facilitate an efficient delivery of fluid through fractal channels connected random network of micro/-nanochannels and enable a better exchange of gases/solute across the membrane matrices through nanovascularized regions. A still further object of the present invention is to design, fabricate and characterize micro/nanovascularized polymer membrane matrices having fractal micro-channels connected to random network of nanochannels for establishing an efficient connection of nanovascularized polymer membrane matrices. An additional object of the present invention is to develop and manufacture bio-inspired 3D-micro/nanofluidic devices useful for applications in tissue engineering, advance drug delivery, self-healing, self-cooling materials, gas/solute exchange processes, diagnostics, solar distillation units and artificial organs in chemical and biomedical industries. These and other objects and advantages of the present invention will become more apparent from the following description, when read with the accompanying figures of drawing, which are however not intended to limit the scope of the present invention in anyway. DESCRIPTION OF THE INVENTION For achieving abovementioned objects, scalable micro/nanotechnologies like electrospinning and Saffman-Taylor instability in Hele-shaw cells are used to generate fractal microstructures in polymers integrated with random network of polymeric nanofibers (Fig. 2). These structures are embedded in an elastomeric polymer membrane matrix and then subjected to solvent etching, which removes the sacrificial micro/nanostructures to leave a polymer membrane matrix with fractal micro-channels integrated with the nanochannel network. Accordingly, the inventors devised method and device for biomimicry of secondary lamella of fish gills through various micro-technologies. This is achieved by designing and developing vascularized polymer matrices membranes having the fractal pattern of micro-channels to mimic the natural vascular pattern of living organisms. This facilitates an efficient delivery of fluid through fractal channels connected random network of micro/nano channels and better exchange of gases/solute across the membrane matrices through nanovascularized regions. So, an efficient connection of nanovascularized polymer membrane matrices is made by designing, fabricating and characterizing micro/nanovascularized polymer membrane matrices, which have fractal micro-channels connected to random network of nanochannels. On connecting these micro/nanovascularized polymer matrix to the fractal micro-channels, they possess enhanced volumetric fluid flow during the capillary action. These vascularized polymer membrane matrices were characterized for the fluid flow and solute exchange process. They also show improved mass transfer across the membrane as compared to micro/nanovascularized polymer matrices connected to external fluidic circuit via rectangular reservoirs. These matrices mimic the secondary lamella of fish gills, and therefore can be used for gas and solute exchange processes in biomedical and chemical industries. In accordance with the present invention, such designs were adopted, in which fractal microchannels were connected to interconnected microporous structure that exists in the leaves of plants. This is because leaves are planner structures having fractal microchannel network connected to microporous spongy mesophyll cells and stomata, which play an active role in passive pumping of water in trees. Thus, leaf inspired micropumps are designed, fabricated and characterized by using scalable micro-technologies, where fractal microchannels (mimicking veins of leaf) are connected to microporous substrate (mimicking spongy mesophyll cells and stomata). The enhanced micro-pumping capabilities and pressure head sustenance have also been demonstrated and the parameters affecting its performance were also characterized by experimental and theoretical methods. Such passive pumping of fluid has the great potential for application in cooling microelectronic circuits, microfluidic circuits, solar distillation etc. The present invention is described with reference to a Polydimethylsiloxane (PDMS) or dimethicone membrane, which is a polymer widely used for the fabrication and prototyping of microfluidic chips. It is a mineral-organic polymer (a structure containing carbon and silicon) of the siloxane family (word derived from silicon, oxygen and alkane). Accordingly, the micro/nanovascularized polymer membrane matrices are primarily made by following two methods: FIRST METHOD: Scalable micro/nanotechnologies (like electrospinning, controlled Hele-shaw cells, solvent etching of sacrificial structures and micro-molding) is used to generate integrated micro-nanostructures. The steps of fabrication process are as follows: a) Preparing a 30% (wt./vol.) solution of polystyrene (196KDa) in Tetrahydrofuran (THF) solvent and homogenizing it by stirring on magnetic stirrer for 3-4 hours. b) Generating fractal structures by taking a drop of above solution and squeezing the drops of above solution between the glass slides and lifting the slides (as in Helle-Shaw cells) to generate fractal structures. The fractal dimension of the fractal pattern depends on the force of squeezing, speed of lifting slides, pattern of lifting, and viscosity of solution. c) Since fractal structures appear like wings of insects or a transparent film with fractal-like patterns, two approaches were used to apply the above pattern for obtaining the fractal channel in PDMS. (i) The first approach involves etching away the film between the fractal pattern obtained in step b) by a quick washing (10 sec) with N,N Dimethyformamide (DMF) and water. This generates fractal patterns in polystyrene without a connecting film between the fingers. These fractal pattern are transferred onto glass-slides coated with semi-baked PDMS by spin coating and used as substrate for deposition of micro/nanofibers by electrospinning. (ii) The second approach involves using the fractal pattern on a glass slide, generated by step b), as substrate for deposition of micro/nanofibers by electrospinning. d) Preparing a 15% (wt./vol.) of polystyrene (PS) (196KDa) in N,N Dimethyformamide (DMF) solvent and homogenizing it by stirring on magnetic stirrer for 3-4 hours. e) Electrospinning of the above solution to obtain micro/nanofibers and depositing on the glass slide with fractal pattern obtained after steps c)(i) and c)(ii) such that fibers are deposited in an area to get physically bonded to the terminal fingers of the fractal structures. Optimizing the electrospinning parameters to enable generation of wet fibers with diameter of 1±0.3um. These wet polystyrene fibers enable it to get fused with polystyrene fractal-structure after releasing the solvent. The electrospinning parameters are (Voltage: 10kV, flow rate: 0.5ml/h, Needle gauge: 24, Electrode distance: 12cm, Temperature: 24°C, Solution: 15% PS (wt./vol.) in DMF). f) Pouring PDMS (10:1) over the glass slides with polystyrene structure obtained after step (e), until the structure gets submerged and thereafter cured over hot plate at 70°C for 3-4 hours. This process generates two types of structures: (I) The fractal structure integrated with micro/nanofiber mesh embedded in PDMS membrane matrix (1-2 mm thickness) (II) An imprint of fractal structure integrated with micro/nanofiber mesh obtained in PDMS (1-2 mm thickness). g) Taking PDMS matrix obtained by step (f) (I) and immersing in DMF solvent to etch away sacrificial structures (fractal structure integrated with micro/nanofiber mesh) of polystyrene. The etching process takes several days (~ 1m) depending on the size of sacrificial structure and during this period, a periodic stirring and sonication is continued to accelerate the etching process with fresh DMF solvent. Taking the PDMS matrix obtained after step (f) (II) and plasma bonding (1 mbar, 20 sec) it with PDMS membrane obtained by spin coating to close the open end of fractal microchannels and nanochannels. h) Obtaining PDMS membrane matrix by the above steps ready to be used for the fluid-flow and solute-exchange study. The aforementioned method yields thin micro/nanovascularized PDMS matrices to be used as 3D micro/nanofluidic devices, The volumetric flow of dye (Figs. 7a-7d) is studied through these micro/nanovascularized polymer matrix having connected to fractal microchannels by capillary action. The presence of dye reflects the continuity of channel network and the connectivity between the fractal microchannels with the nanochannel network. Further, time lapse microscopy and image processing also demonstrated enhanced volumetric fluid-flow during capillary action through these micro/nanovascularized polymer matrix having connected to the fractal microchannels as well as improved mass transfer across these membranes in comparison to the micro/nanovascularized polymer matrices connected to external fluidic circuit via rectangular reservoirs. These fractal micro-reservoirs proved to be a better candidate for connecting micro/nanochannel networks in micro/nanofluidic devices and the mass transfer efficiency of the vascular membranes is found to be 10""ml/min. SECOND METHOD: Scalable micro/nanotechnologies (electrospinning, 3D printing, solvent etching of sacrificial structures and micro-molding) are used to generate integrated micro-nanostructures. The steps of fabrication processes are as follows: A) Designing and fabricating the fractal mold with 3D printer in Acrylonitrile butadiene styrene (ABS) and depositing random micro/nanofibers (polystyrene) as sacrificial structure in between fractal structures to generate the pattern resembling natural vasculature. B) Pouring PDMS (10:1) in the mold obtained after step (A) and curing it over hot plate at 70°C for 3-4 hours. Gently removing the mold (2mm thick) with open fractal micro-channels connected with micro/nanofibers embedded in PDMS matrix. C) Submerging the above PDMS matrix obtained after step (B) in DMF solvent and allowing the fibers to be etched away. The etching process is accelerated by stirring over magnetic stirrer, which requires several days. D) Closing thin PDMS matrix with open channels by bonding with PDMS membrane (~20|jm) coated on paraffin wax paper, by plasma bonding (1 mbar, 20 sec). This method yields thin 3D micro/nanofluidic devices with fractal micro-channels for fluid flow and random microvascular section as a site for gas exchange. These devices are structurally characterized for presence of channels and their connectivity, but no fluid-flow and mass transfer operations are carried out. FABRICATION PROCESS OF MICROPUMPS INSPIRED FROM LEAVES The method for designing, fabricating and characterizing leaf inspired micropumps with fractal micro-channels connected to microporous substrate is used by combining the microfabrication processes like controlled Hele-Shaw cells, micro-molding, and spin coating. The method steps are as follows: (1) Preparing an alumina based ceramic solution in HDDA and homogenizing by stirring on magnetic stirrer for 3-4 hours. (2) Generating fractal structures by taking a drop of the above solution. Generating fractal structures in a controlled way, by squeezing these drops between the glass plate and then lifting the slides (as in Hele-Shaw cells). Here, the fractal dimension of fractal pattern depends on the squeezing force, speed of lifting slides, pattern of lifting, and solution viscosity. Heat curing the fractal shaped pattern at 120°C on a hot plate for 7-8 hours and sticking the fractal structure to the glass plate, thereby to facilitate in its use as a mold. (3) Pouring PDMS (10:1) over the glass plate having fractal ceramic mold, until the structure is submerged up to 5 mm thickness and thereafter heat curing it over hot plate at 70°C for 3-4 hours. Ensuring the gradient in PDMS thickness by placing a ceramic mold in tilted position (-20°) to make polymer matrices near the parent generation of the channels thicker than the polymer matrices near the terminal channels to enable easy fluidic connections with external reservoir to mimic the architecture of leaves. Obtaining PDMS matrix with open fractal micro-channel net, after careful removal from the mold. (4) Preparing PDMS (10:1) and spin coating at 800rpm for 2 min on a paraffin wax paper and allowing the coated film to be partially cured at room temp for 24hrs. Thereafter, sticking it to microporous filter paper for occupying less area than the filter paper area. Removing the paraffin wax paper carefully for adhering one side of partially cured PDMS membrane to filter paper, while other side remains sticky and ready for bonding with microchannel network in PDMS matrix obtained in step (3). (5) Thoroughly washing PDMS matrix obtained in step (3) and then bonding to the partially cured PDMS membrane adhering to microporous filter paper for closing the open channels of PDMS matrices and to enable terminal branches touching the microporous substrate. This configuration mimics the leaves, in which microporous substrate acts as spongy epithelial cells matrix with stomata, fractal microchannel net represents the venation system and PDMS matrix assumes the role of dense palisade cells and waxy cuticle layer. (6) Connecting the device obtained by above process via a tube to pump water from the reservoirs. This leaf inspired micropump demonstrates enhanced fluid pumping rate and is able to sustain the pressure head. This method also yields a micro/nanofluidic based leaf inspired micropumps., which exhibit an enhanced volumetric pumping of water and pressure head sustenance is as compared to the prior art. The parameters affecting its performance are also characterized by experimental and theoretical methods. SUMMARY OF THE INVENTION In accordance with the present invention, there is provided a bio-inspired 3D-micro/nanofluidic device manufacture by a scalable fabrication process, wherein the device comprises a thin micro/nanovascularized membrane matrices with fractal microstructures in polymers, such as microchannels and nanochannels connected to interconnected microporous structure similar to the secondary lamella of fish gills for achieving enhanced fluid-flow and mass transfer capabilities. Typically, the microstructures structures are embedded in an elastomeric polymer membrane matrix and the sacrificial micro/nanostructures is removed by subjecting them to solvent etching for producing a polymer membrane matrix with fractal microchannels integrated with the nanochannel network interconnected microporous structures. Typically, the thin micro/nanovascularized membrane matrices are made of Polydimethylsiloxane (PDMS) or dimethicone membranes. In accordance with the present invention, there is provided a method for fabricating a bio-inspired 3D-micro/nanofluidic device; the method comprises the following method steps: • Filling the syringe with polymer solution and electrospinning a continuous polymer fiber for depositing a nanofiber mat on a collector and making random sacrificial micro/nanofiber mesh thereof; • Obtaining an embedded PDMS matrix by embedding the above random sacrificial micro/nanofiber mesh in thin PDMS matrices; • Subjecting the above embedded PDMS matrix with micro/-nanofibers for solvent etching, preferably in N,N Dimethyformamide (DMF) by putting in a container resting on a magnetic stirrer to obtain a thin micro/nanovascularized PDMS matrix; and • Plasma bonding the above thin micro/nanovascularized PDMS matrix to a glass slide and punching rectangular Source reservoir and Sink reservoir are punched in to obtain a 3D micro-nanofluidic device. In still another embodiment of the invention, the method comprises the following method steps: (a) Preparing a solution, preferably a 30% (wt./vol.) solution of polystyrene in Tetrahydrofuran solvent and homogenizing it by stirring on magnetic stirrer for 3-4 hours; (b) Generating fractal structures by taking a drop of above solution and squeezing the drops of above solution between glass slides, e.g. in a Hele-Shaw cell; (c) Etching away the film between the fractal structures obtained in step b) by a quick washing, preferably for 10 seconds with a 15% (wt./vol.) solution having N,N Dimethyformamide (DMF) and water and transferring these fractal structures onto a glass-slide coated with semi-baked PDMS by spin coating and using them as a substrate for depositing the micro/nanofibers by electrospinning; or Using the fractal structures generated in step b) on a glass slide as a substrate for depositing the micro/nanofibers by electrospinning and using them as a substrate for depositing the micro/nanofibers by electrospinning; d) Preparing a solution, preferably a 15% (wt./vol.) solution of polystyrene in N,N Dimethyformamide (DMF) solvent and homogenizing it by stirring on magnetic stirrer, preferably for 3-4 hours; e) Electrospinning of the above solution to obtain micro/nanofibers and depositing on the glass slide with fractal pattern obtained after either of the method step under step c, in an area for physical bonding with the terminal fingers of the fractal structures; f) Optimizing the electrospinning parameters to enable generation of wet fibers of a predetermined diameter, preferably a diameter of 1±0.3pm for enabling their fusion with polystyrene fractal-structure after releasing the solvent; g) Pouring Polydimethylsiloxane (PDMS) in a predetermined ratio, preferably in a ratio of 10:1 over the glass slides with polystyrene fractal-structure obtained after step (e) until the structure is submerged and thereafter curing over a hot plate, preferably at 70°C for 3-4 hours to obtain the fractal structure integrated with micro/nanofiber mesh embedded in PDMS membrane matrix, preferably of 1-2 mm thickness; h) Obtaining an imprint of above fractal structure integrated with micro/nanofiber mesh embedded in PDMS membrane matrix, preferably of 1-2 mm thickness; i) Immersing the above imprint of embedded PDMS matrix in DMF solvent to etch away sacrificial structures (fractal structure integrated with micro/nanofiber mesh) of polystyrene over long period, preferably over several days; more preferably over one month depending on the size of sacrificial structure and continuing a periodic stirring and sonication during this period to accelerate the etching process with fresh DMF solvent; j) Taking the PDMS matrix obtained after step (i) and plasma bonding thereof, preferably at 1 mbar for 20 seconds with the PDMS membrane obtained by spin coating to close the open end of fractal microchannels and nanochannels; and k) Obtaining the PDMS membrane matrix ready to be used for the fabricating the bio-inspired 3D-micro/nanofluidic device. In another embodiment of the invention, the method comprises the following method steps: (I) Fabricating the fractal mold, preferably of 2mm thick, by using a 3D printer and from Acrylonitrile butadiene styrene

Documents

Application Documents

# Name Date
1 Power of Attorney [28-04-2017(online)].pdf 2017-04-28
2 Form 3 [28-04-2017(online)].pdf 2017-04-28
3 Form 1 [28-04-2017(online)].pdf 2017-04-28
4 Drawing [28-04-2017(online)].pdf 2017-04-28
5 Description(Complete) [28-04-2017(online)].pdf_198.pdf 2017-04-28
6 Description(Complete) [28-04-2017(online)].pdf 2017-04-28
7 Assignment [28-04-2017(online)].pdf 2017-04-28
8 Abstract1.jpg 2018-08-11
9 201721015210-OTHERS [30-12-2021(online)].pdf 2021-12-30
10 201721015210-EDUCATIONAL INSTITUTION(S) [30-12-2021(online)].pdf 2021-12-30
11 201721015210-FORM 18 [31-12-2021(online)].pdf 2021-12-31
12 201721015210-RELEVANT DOCUMENTS [14-01-2022(online)].pdf 2022-01-14
13 201721015210-POA [14-01-2022(online)].pdf 2022-01-14
14 201721015210-FORM 13 [14-01-2022(online)].pdf 2022-01-14
15 201721015210-FORM-8 [24-02-2022(online)].pdf 2022-02-24