Microfluidics: Escalating Chapter in Biomedical Research.
How marvelous the thing is! An organ is developed, functions of the organ are observed, specific disease-related drugs are discovered, even the most prodigious fact is that the cancerous cells are separated from the normal cells within a chip in real-time, still again micro-scale range. Yes, Progressive research and evolvement of ‘Microfluidic Devices’ makes it possible. It’s a challenging field with the combination of engineering knowledge, mathematics, chemistry, physics along with biological knowledge in the case of biomedical applications.
Microfluidic Devices
Microfluidic devices are analytical device which deals with any kind of fluids or biological sample within a microliter range. This field adds a neoteric dimension in biomedical research. Microfluidics is the science of manipulating and controlling fluid of microliter ranged consisting of micro-channels which are either etched or molded into a material forming the microfluidic chips to get desired output (mix, pump, separate, etc.)
Types of Microfluidic Devices
Though there are several classifications of microfluidic devices according to its applications, most commonly used category is continuous-flow microfluidics and the digital microfluidics (DMF). According to the power supply, microfluidic chips can be active (when the power supply source is present) or passive (when there is no power source). Microfluidics can also be worked as micromixer and micropump.
The above figure represents a simple active micromixer, which was my primary work on microfluidics. The objective was to mix the single-phase fluids of two different concentrations under the laminar flow, diffusion through convection and the effects of electric field. The simulation was done by COMSOL Multiphysics software.
To mix and separate are the vital part between the sample used for microfluidics applications are under the continuous-flow mixing. This constant mixing process interacts with external energy sources and complex geometry configurations. The current range of continuous separation method includes magnetofluidic separation, inertial microfluidics, acoustofluidic separation, dielectrophoretic separation, optofluidic separation.
Digital microfluidics (DMF) deals with droplets based applications, usually in the microliter scale or smaller. It also involves with dielectrophoretic technique, electrowetting -on-dielectric (EWOD) technique, magnetic particle-based technique, liquid-marble-based DMF, etc.
Modeling Methods of Microfluidics
Numerous methods are used to model microfluidic chips. Among them, Finite Element Method or FEM is widely used as it has high accuracy over the other methods like Finite Difference Method (FDM), Finite Volume Method (FVM) and Boundary Element Method. FEM deals with the differential equation of every node under several boundary conditions are multiplied by a weight function before being integrated over the domain to extract the boundary information.
Materials Used for Microfluidics
Selecting materials for microfluidics is a concerning matter. Materials should be applications friendly and biocompatible in the case of biomedical applications. Most commonly silicon, glass, and polymer is widely used for creating microfluidic devices.
Silicon is used as microfluidic material because of its resistance to organic solvent, the ease in metal deposition, it’s superior thermal conductivity, surface stability. But silicon microfluidic chips are difficult to maintain for optofluidic because of its significant optical opacity. Glass is the most widely used microfluidics material as being an insulating, amorphous material glass is chemically inert, biocompatible, has optical transparency and excellent high-pressure resistance. Polymer plays a spacious role as a material to build microfluidic chips. Especially, Polydimethylsiloxane (PDMS) is used for its permeability property, optical transparency, elastomeric properties, robustness, non-toxicity, biocompatibility, relatively low cost.
Fabrication Processes of Microfluidics
Patterning and fabricating microfluidic devices are the intellectual task because the efficiency of the device depends on the way it will be patterned. So perfect design pattern of the devices before the fabrication process is a must. For the fabrication of microfluidic devices, different ways exist including wet and dry etching, thermoforming, polymer ablation, polymer casting, 3D printing, etc.
In the case of wet and dry etching, it is the process of creating the template for the functioning area and for this, some region of a chip material is protected and the materials of functional part are removed to put samples. It is the primary process of lithography. During the thermoforming process, a material is heated to it soft to put it in a particular form by injection molding or heat embossing and commonly used in case of plastic material. Polymer ablation is also a fabrication process where microstructures are used as direct writing processes. In polymer casting method a mold is created and polymer is used in the molded part to replicate for fabricating a microfluidic chip. 3D printing is the most commonly used technique in microfluidics fabrication and in this process, a ledge of a material is added on the top of the previous ledge of the same or different material and can be easily used in prototyping.
Applications of Microfluidics
In biomedical research, microfluidics has spacious applications and this field leads the research in a new direction. As being a multidisciplinary field, it has a great paradigm in MEMS-based devices. In Genomics, microfluidics lead to a potential dimension in Next Generation Sequencing (NGS), DNA Sequencing and Mutation Detection, DNA Purification, etc. In the case of Cell Sorting, an electrokinetic microfluidic device has been developed to separate abnormal cells (cancerous cells) from the normal cells, to separate different types of blood cells using electrophoresis. The most exciting application is Organ-on-a-chip in this field which deals with the physiological mimicry of an organ, culture of tissues and the development of stem cells for the mimicry of an organ on a single chip to observe its working mechanisms, the root of its origin, to culture organ’s tissues, etc.
After that, the most prominent application of microfluidics is Drug discovery. The foreword of microfluidics is inexpressible in this field. To select a target is the first step in this case and the target can be Gene, DNA, Protein or any organ and this type of microfluidic device can express, separate, label and quantify target to discover and deliver the drugs and ‘SlipChip’ is this kind of microfluidic device which is developed for crystallization of protein-membrane, to discover the most efficient drug better than ‘Insulin’ for diabetes through testing on the mimic of Beta-cell, which is cultured within a microfluidic chip. In Diagnostic, point-of-care devices have been created and it is a paper-based microfluidic device which is called ‘Micro pad’ that provides prompt diagnosis at the patient’s care site. Besides those, microfluidics diffuse its footprints in the different field of life science.
Advantages of Microfluidic devices
The advantages of microfluidics are colossal. As the name regards, this field deals with the samples of micro-scale range so that a small sample volume is needed, and moreover, the use of expensive reagents, the production of waste becomes reduced. As the fabrication methods and materials of microfluidics are application-based, it can be easily determined which materials and methods are needed to apply for the specific application. Having micro-channels is the most common feature of microfluidics and this feature enables it to integrate other systems with the device. The same device can be used to perform several functions at a time which makes it low time consuming and relatively low-cost device.
Working Challenges with Microfluidic Devices
As microfluidic devices deal with a small volume of samples, the sensitivity and accuracy are the vital issues to consider. Besides, being a multidisciplinary field, it deals with multiphysics terms like pressure, force, velocity, fluid mechanics. So modeling should be computationally efficient so that the desired device performance can be achieved by keeping pace with the change of physical characteristics of the sample. Material selection is another vital issue for microfluidic devices, especially, in case of organ-on-a-chip, as it deals with the physiological and anatomical mimic of an organ or a part of an organ so creating the optimized environment of Stem cell division and cell culture is a challenge.
Future Directions
Microfluidics has some limitations but it’s advantages outweigh those. It is a cost-effective, portable and small-scale chip and it is easily affordable in the laboratory which leads to an increase in the applications field of microfluidic through efficient research and analysis. Moreover, being an integrated system, several analyses can be done within the same chip, at the same time and this advantage focuses the light on using the microfluidic chips as a universal molecular diagnosis platform. Finally, microfluidics can be the potential tool in the biomedical research field through rapid development and with robust applicable ideas.
