Microfluidic Technology Advances: “Fabrication and Applications of Microfluidic Devices: A comprehensive Review

Microfluidics is "the science and technology of systems that process or manipulate small (10–9 to 10–18 L) amounts of fluids, using channels with dimensions of tens to hundreds of micro meters," according to George Whitesides, one of the most significant figures in this field. These tiny microscale devices are practical tools for performing tasks like separations, reactions, and chemical detection . In the literature, microfluidic devices are sometimes referred to as microreactors , lab-on-a-chip , or organ-on-a-chip  depending on their use and functional characteristics. Microfluidic chips can be produced using a variety of fabrication techniques and a wide range of materials, depending on their intended function. The potential for advancements in the field of microfluidics develops suddenly, offering new views to both the academic and industrial sectors, since many production approaches have already been published in the literature and applied in practice. Additionally, as a number of commercially available instruments are already used for pregnancy at-home testing, this technique shows promise for everyday applications; virus (e.g., human). Since flow in microfluidic devices is nearly always laminar rather than turbulent , mixing often happens by molecular diffusion. The tiny distances inside microfluidic channels allow for full mixing in a matter of seconds or minutes, whereas mixing based on diffusion could take days in traditional flask-based systems. Another benefit of such small dimensions is the huge reduction in sample and reagent volumes, which lowers reagent costs and waste production. A platform with a tiny footprint can be created by integrating several parts and procedures on a single device. The "micro–Total Analysis System" (micro TAS, mTAS) concept is driven by this integration potential, which allows for "sample in-answer out" capabilities with brief analysis by allowing all components of an analysis process—from sampling to detection—to be completed on a single device.

Advantages of Microfluidic Device:

• Utilizing extremely small quantities of samples and reagents in the laboratory
• Cost savings as a result of using fewer costly reagents
• High sensitivity and resolution for molecular separation and detection
• smaller footprint of analytical and diagnostic equipment in comparison to large laboratory equipment’s
• Faster results and shorter analysis times
• More flow control is possible when fluids flow laminarly, or smoothly, via small channels.
• More microscale control over sample concentration and experimental conditions.

Disadvantages of Microfluidic Device:

• In microfluidic device, drug absorption may be affected by PDMS.

Results are design dependent.

• There is no high throughput.
• They can be expensive.
• Challenges in manufacturing high production modes.
• Challenges in mixing, interface to macro and nano size.
• Detection and quality control are more difficult.

Application Of Microfluidic Devices:

1. Glioblastoma study: current status and future directions:

One of the most dangerous primary brain tumours is glioblastoma (GBM). This tumour has a poor prognosis and is the most difficult to treat. A successful cure for the disease is improbable due to its traits of genetic variability and frequent recurrence. GBM stem cell-like cells (GSCs) and the microenvironment are important factors in GBM recurrence and treatment failure, according to mounting data. Appropriate methodologies, techniques, and model systems that closely resemble actual GBM situations are needed to better understand the mechanisms behind this disease and to generate more effective therapeutic strategies for treatment. Microfluidic devices, which simulate the in vivo brain milieu, offer a highly helpful tool for analysing the activity of GBM cells, their relationship to tumor malignancy, and the effectiveness of various medications.

2. Experimental Investigation of Microfluidic Device for Platelet Activation: The purpose of this study was to increase platelets without the use of pharmacological stimulants.

Method: This study has suggested two different kinds of mechanical platelet activation techniques. A microfluidic chip created using the shear-induced platelet activation technique is the first. The second is a piezo-based ultrasound-assisted device that uses an ultrasonic pulse (0.55 and 1.1 MHz) to stimulate platelets and activate them. To find the ideal shear stress characteristics, three distinct microfluidic chip designs were developed: pillar-shaped (1030 μs, 1656 shear pulses, and 48.1 dyne/cm2), 40-nodes (2765 μs, 1440 shear pulses, and 95.5 dyne/cm2), and 8-nodes (2789 μs, 288 shear pulses, and 98.3 dyne/cm2).

3. Microfluidic device for multiplexed detection of fungal infection biomarkers in grape cultivars: A proper treatment of the plant by preventing the pathogen's growth without overusing fungicides depends on early detection of fungal infections, which have increased as a result of various environmental variables. In order to identify contaminated grape cultivars, we provide in this work a microfluidic-based method for a multiplexed, point-of-need detection device. With a total assay time of less than seven minutes and LODs of 15 μM, 10 μM, and 4.4 nM, respectively, the system is based on the simultaneous detection of three plant hormones: salicylic, azelaic, and jasmonic acids. The microfluidic technology was used to examine the grapes in addition to standard methods including enzyme-linked immunosorbent assay and high-performance liquid chromatography. The microfluidic technology was able to differentiate between several infection types in addition to differentiating between healthy and infected samples.

4. Development of paper-based microfluidic device for the determination of nitrite in meat: The content of nitrite in pork was measured in this work using a microfluidic paper-based analytical device (µPAD), and the coffee-ring effect was examined to improve the limit of detection. By printing and heat-treating the cellulose-based filter paper to enable wax penetration, wax channels were created and embedded into the paper to create the µPAD. By tracking the colorimetric reaction between nitrite and the additional Griess reagent, the quantity of nitrite was ascertained. By examining the inner-chamber reaction, the device's limit of detection for nitrite in pork was found to be 19.2 mg kg-1; however, if the coffee-ring region was examined, it might be as low as 1.1 mg kg-1. Within fifteen minutes, the entire analysis might be finished.

5. A microfluidic device for digital manipulation of gaseous samples: In the present study, we introduce a novel method that uses a digital microfluidic platform (DMFP) to manipulate gaseous samples, including alkanes from n-hexane to n-nonane. To capture and release the samples based on their controlled temperature, the DMFP primarily uses interconnected micropreconcentrators (μPCs). We demonstrate that the DMFP can carry out all fundamental tasks in digital microfluidics, including adding, releasing, and moving samples as well as sorting and trapping samples. We measured the breakthrough volume of alkanes on a Tenax TA adsorbent as a preliminary illustration of a more intricate programmable application of our DMFP. The findings aligned with values tabulated using common laboratory equipment. More sophisticated programmable gas microfluidics digital devices could be made possible by this DMFP, and the Sensing.

Components Of Microfluidic Device:

1. Channels: channels are a crucial component of microfluidic devices, playing a vital role in fluid manipulation and control. Functions of channels in microfluidic device are,

Fluid transport

Fluid mixing

Separation

Reaction

2. Chambers; One particular kind of microfluidic device that regulates fluid movement on the chip is a microfluidic chamber. Despite being relatively new, this technology is crucial for uses like as drug detection and cell culture.

Five Typical Microfluidic Chamber Types:

1. Chambers of Reaction
   Microfluidics reaction chambers, often referred to as interaction chambers, use their microchannels to enable minute reactions between various substances.
2. The Organ-on-a-Chip

A specialized microfluidic chamber system that replicates the microenvironments seen in the human body is called an organ-on-a-chip. For instance, a microfluidic chip could be used to replicate a liver or  kidney.

3.  Chambers of Electro kinetics

Researchers can examine how particular liquids move in response to different electric fields (e-fields) using this kind of chamber. With a number of microchannels tailored for every use, electrokinetic chambers are usually constructed from sturdy materials like glass and polymers.

4.  Chambers for Immunoassay
    The detection of particular biological disease indicators, such as proteins, antigens, and antibodies, is made possible using microfluidics technology. Microfluidics is an effective option for use cases such as these because, in contrast to conventional immunoassay procedures, it may produce findings quickly without using the full sample.

Food toxicity testing:

Point-of-care (POC) testing

Environmental testing

e)  Generators of Concentration Gradients (CGGs)

For precise research into how particular biological systems react to particular gradients of a substance—a process with numerous applications in the life sciences and pharmaceuticals—stable concentration gradients are necessary.

3. Microfluidic Valves:

A microvalve is a tiny valve that finds extensive application in numerous domains. It can function as a         closing switch, control the flow rate, and regulate the flow between two fluid ports. The capacity to control fluid flow through valves is crucial in many microfluidic applications.

A] Microfluidic valves that are active
 Active valves typically rely on external systems to supply power and regulate the actuators.

B] Microfluidic passive valves
The fluid being controlled determines the operational condition of passive microvalves.

4. Pumps: pumps are essential components of microfluidic devices, enabling precise fluid control and manipulation.

5. Actuators:

Actuators play a crucial role in microfluidic devices; enabling precise control over fluid flow, pressure, and temperature.

6.Mixers:
A fundamental procedure needed for many biological applications is mixing. Laminar flow conditions at the microscale restrict mixing to diffusion.

anufacturing Methods:

The current techniques used for fabricating micro?uidic devices include micro-Machining, soft lithography, embossing, in situ construction, injection moulding, and laser ablation.

Micromachining:
Silicon micromachining was one of the first methods used in microfluidics and is frequently utilized in microelectromechanical systems (MEMS). Silicon may be used to create complex systems.

2.Soft Lithography: Lithography quicker, less costly, and less specialized technique of device manufacture was required to encourage the broad usage of microfluidic devices in biology. Bell Labs pioneered elastomeric micromolding in 1974 when scientists created a method for shaping a soft substance from a lithographic master.
Generally speaking, soft lithography is the process of molding polydimethylsiloxane (PDMS), a two-part polymer consisting of an elastomer and a curing agent, using photoresist masters.

3.In Situ Construction

Microfluidic tectonics is a recently developed technique for building microfluidic devices in situ utilizing photo definable polymers. The idea creates microfluidic devices using lithography, laminar flow, and liquid phase photopolymerizable materials. A shallow chamber is filled with the liquid prepolymer, and it is exposed to UV radiation using a mask.
Despite offering a comparatively inexpensive substitute, the device's size is constrained by the mask's resolution and the polymer's polymerization effects.

A particularly promising method for producing microfluidic devices at a reasonable cost is injection moulding. To make thermoplastic polymer materials malleable and soft, they are heated above their glass transition temperature. A cavity containing the master is filled with molten plastic. However, from a cost standpoint, injection molding is the favored technique for high-volume manufacturing because it is far faster than hot embossing. Injection molding's limitations for microfluidics include material selection and resolution.

5. Other Method

Laser ablation of polymer surfaces followed by bonding to create channels is another technique for creating microfluidic devices. Multi-layer channel networks can be easily created by adapting the technique. Fabrication of Microfluidic Device.

Microfluidic Device Materials

Choosing the best material for device fabrication is one of the essential processes in microfluidic applications. Durability, ease of fabrication, transparency, biocompatibility, chemical compatibility with the suggested reagents, meeting the reaction's temperature and pressure requirements, and the possibility of surface functionalization are additional crucial characteristics that must be taken into account when selecting the material.
 Since silicon is readily available, chemically compatible, and thermostable, it is frequently used in the construction of microfluidic systems.

5. Chip Fabrication Methods:

Due to a number of technological developments from other domains that have attracted attention from researchers and been modified for chip manufacturing, microfluidics has advanced significantly in a comparatively short period of time.

6. Chemical Processes:

Glass and silicon microfluidic channels have long been made using a variety of chemical production techniques. Electrochemical discharge machining and wet and dry etching are the most often used chemical processes.

7. Mechanical Processes

One of the earliest techniques for creating microfluidic devices was micromachining, which was taken from the already-established field of semiconductors. While maintaining acceptable dimensional accuracy and surface roughness, mechanical procedures must enable the creation of surfaces devoid of cracks. These methods work well for processing silicon and glass, but they can also be applied to the replication master generation of polymer-based devices. Low costs, great degrees of flexibility, and the ability to be combined with other processes are the advantages of techniques like mechanical cutting, abrasive jet machining, and ultrasonic machining for the creation of intricate 3D structures. However, the primary drawback of mechanical fabrication techniques is their lower productivity and accuracy when compared to lithographic techniques.

6. Laser-Based Processes

Although lasers are generally costly equipment, they are thought to be a more accessible fabrication method when compared to the expense of cleanroom facilities. Furthermore, without the risks connected with chemical production techniques, laser ablation facilitates the quick and flexible creation of microfluidic patterns on a variety of materials. In principle, lasers use the stimulated emission of electromagnetic radiation to optically enhance light. The impact of thermal deterioration produces a microstructure that engraves the surface of the working material.
A traditional method for creating 3D polymer structures, stereolithography falls under the category of laser-based fabrication procedures. This technique is perfect for quickly producing extremely delicate details.