Scientists initiated research into the potential applications of these devices for various objectives, establishing the groundwork for Lab on a Chip technology. At Stanford University, the first true lab-on-a-chip was developed using these fabrication techniques in 1979 for gas chromatography on a silicon (Si) wafer [3]. The miniaturization of traditional laboratory processes onto microscale devices is a central aspect of this technology, which offers substantial benefits over conventional laboratory techniques.

Lab-on-a-chip (LOC) is a device that combines one or more laboratory functions onto an integrated circuit (sometimes referred to as a "chip") that measures only a few square millimeters to a few square centimeters. The goal of the device is to achieve high-quality screening and automation [4]. These platforms offer miniaturized, automated, integrated, and parallelized chemical and/or biological analyses. They provide a cost-effective, efficient, manageable, and high-performing solution for bio-chemical assays on a significantly smaller scale compared to traditional laboratory tests. LOC devices have the capability to manage fluid volumes that are incredibly small, even reaching less than pico-litres [5]. They have the capacity to examine a small number of micro-droplets of whole blood, plasma, saliva, tears, urine, or sweat for medical diagnostic purposes. They use microfluidics, the science that deals with manipulating extremely small amounts of liquid. LOC devices, also termed micro total analysis systems (TAS), are a specific category within the realm of microelectromechanical systems (MEMS) devices [6]. Typically, these devices are constructed from silicon, glass, or polymer (Table 1) and are designed with small channels, valves, and pumps that are capable of moving, blending, and examining proteins, DNA, hormones, pathogens, and various other substances found in bodily fluids to achieve a specific testing result. The minute liquid streams, resembling hair-thin strands, are created by the fluid droplets. These streams can be moved around with the aid of air pressure, mechanical forces, electricity, or even sound, allowing for precise transportation to their intended location. They can then interact with other chemicals, providing valuable insights into the existence of chronic illnesses or invisible pathogens. LOC devices have the capability to integrate a range of detection components, such as optical sensors, electrodes, or biosensors. This integration allows for the continuous monitoring and analysis of samples [7]. This review article comprehensively explains how Lab-on-a-Chip (LOC) technology utilizes microfluidics, manufacturing materials, and microfabrication techniques.

LOC devices are useful for a variety of diagnostic tasks, such as tracking chronic illnesses, looking for genetic problems, and identifying infectious diseases. The objective of our review is to present a detailed note on how LOC devices are being used to diagnose various chronic infectious diseases to date. The names of key diseases are illustrated in Figure 1. But our question is, can LOC technology be used for diagnosing all other diseases in the future as well? However, the potential of LOC technology extends beyond medical diagnostics, as LOC devices offer exciting applications in diverse domains, including clinical diagnostics, point-of-care testing, pharmaceuticals, and personalized medicine [8]. But what are the ethical and societal implications of the widespread use of LOC devices in healthcare and other fields? An emerging trend in Lab-on-a-Chip (LOC) technology is Organ-on-a-Chip, which is discussed in detail in Table 2. By examining recent advancements, broader applications, challenges, developments, and future trends in LOC technology, this article aims to illustrate how these miniature laboratories could become an essential tool in our defensive measures against evolving pathogens and significantly enhance our response to infectious diseases by providing faster, cheaper, and more precise diagnostics, potentially reshaping the landscape of medical technology, biomedical engineering, molecular biology, and public health.

Microfluidics-Basic Principle Behind LOC

The core technology behind lab-on-a-chip is microfluidics, which manipulates less than picoliters of fluid. A microfluidic chip is composed of a series of grooves or microchannels that are etched onto diverse materials such as glass, silicon, and polymers like polydimethylsiloxane (PDMS) or polymethylmethacrylate (PMMA) [18]. The width and height of microfluidic channels usually fall within the range of 1 to 1000 mm. The engraved grooves or microchannels found on silicon or polymer layers are intentionally created to facilitate effective mixing. A single chip that can fit in your hand has the capability to incorporate millions of microchannels, with each channel measuring in mere micrometers. A typical microfluidic structure needs reagents and a sample in the range of 100 nl to 10 ml. This procedure facilitates the effective management of limited quantities of liquids (for example, reagents used in biochemical reactions). A wide range of diverse techniques for driving fluids in microfluidics have been documented. However, the two most commonly used fluid driving modes are electroosmosis [19] and hydraulic pressure [20]. On applying an electric field, the charged fluid engages with the surface of the chip, resulting in a pumping action that drives small amounts of liquid forward; this is called electroosmosis. In hydraulic pressure, external pressure forces fluids through microchannels in a controlled and precise manner.

The development of lab-on-a-chip is closely intertwined with the history of microfluidics. Delving into the past, the initial microfluidic technology emerged during the early 1950s, as scientists endeavored to administer minute quantities of fluids in the nanoliter and sub-nanoliter range [21]. Microelectronics and microfluidics have similar origin stories. During the early 1950s, scientists adapted the photolithography technique, utilizing light to produce more intricate micro-sized transistors in silicon, as shown in Figure 2. During the late 1980s and early 1990s, silicon micromachining enabled the creation of various microfluidic structures, including microvalves and micropumps. These advancements laid the foundation for integrating microfluidics into complex liquid handling protocols, thus enabling automation [22]. Over the past twenty years, numerous researchers have dedicated a significant amount of time to the advancement of micropumps, microvalves, micromixers, and other microfluidic liquid handling devices. This marked the beginning of the rapidly developing field of "micro total analysis systems," or "lab-on-a-chip" (µTAS).

Microfabrication is essential for the existence of microfluidics. Huang [23] investigated that CAD (Computer-Aided Design) software is frequently employed to visualize and enhance the microfluidic design prior to fabrication. The design must consider variables like flow rates, pressure drops, and channel dimensions in order to guarantee optimal fluid flow and enhance device functionality. Microfabrication plays a crucial role in generating geometrically defined patterns for microfluidics applications, which involve controlling fluids through devices like Lab-on-Chips and Organ-on-Chips on a sub-millimeter scale. This review answers the question of D. Mark et al., “Will microfluidics remain a toy for academic and industrial research or will it finally make the transition to an end-user product?” [24], as the first commercial microfluidic lab-on-a-chip-based systems were presented in 1999 in the domain of life sciences [25]. Microfluidic devices provide distinct benefits in the manipulation of samples, mixing of reagents, isolation, and detection. Rey Gomez [26] studied that this cutting-edge technology is particularly well-suited for the efficient handling of valuable and hard-to-acquire samples and reagents.

MANUFACTURING MATERIALS

LOC devices are hybrids that are typically made of materials such as silicon, glass, paper, and polymers like polydimethylsiloxane (PDMS), acrylic, polyester, or polymethylmethacrylate (PMMA) [27-29]. The manufacturing procedure of LOC devices involves a diverse array of circumstances, encompassing exposure to elevated temperatures, corrosive substances, and water. These devices comprise a range of elements, such as microfluidic channels, valves, pumps, mixers, separation modules, and detection components. Cowley [30] revealed that silicon, glass, or polymers are appropriate materials for fabricating the microfluidic parts of the chips, while metals such as gold, platinum, or titanium are employed for the conducting components [30]; silicon dioxide, silicon nitride, and titanium nitride are for insulation and passivation [31,32]. The substrate, known as the base material, is used for fabricating microfluidic channels, chambers, and components. Now let's review all these substrate materials one by one. Each material has its own benefits and drawbacks, as shown in Table 1.

Silicon

Based on silicon, the first lab-on-a-chip was formed [33], which is highly compatible with integrated electronic components. Silicon was first selected due to its monocrystalline structure, resistance to organic solvents, simplicity of use in metal deposition, resistance to a broad range of chemicals, excellent mechanical properties, and high thermo-conductivity. It possesses exceptional mechanical characteristics, providing high durability and stiffness that allow for the creation of complex microarchitectures. Kuryliuk [34] demonstrated that silicon's remarkable thermal conductivity allows for rapid temperature changes, making it well-suited for tasks that demand accurate heating and cooling. However, despite all these benefits, it also has some limitations as a substrate for Lab-on-a-Chip devices, including its high cost and lack of optical transparent (except for IR) compared to glass and polymers. A hygienic room and a deep understanding of microfabrication are essential for this process. Team [35] highlighted that despite silicon being considered outdated by some, it remains a viable option for the innovation of certain complex lab-on-a-chip applications in industry and continues to be utilized in research settings.

Glass

Glass and then polymers quickly took the place of silicon. Most high-end labs on chips are made of glass. Glass is optically transparent, chemically inert, has surface flatness, thermal shock resistance, and high mechanical stability, is compatible with biological samples, and has low non-specific adsorption. These characteristics make it a popular material for life science and pharmaceutical applications. Borosilicate glass and fused silica are the two most commonly utilized forms of glass [36,37]. Glass is an excellent choice for the advancement of various lab-on-a-chip applications, making it a highly appropriate candidate for industrialization. Nevertheless, the formation of a glass lab-on-a-chip necessitates the utilization of clean rooms and the expertise of researchers well-versed in microfabrication techniques. Glass lab-on-a-chip may not be the most ideal choice for research laboratories. Conversely, when structures with high aspect ratios are needed, such as very deep and narrow channels, silicon proves to be a more appropriate substrate material [38].

Polymer

Polymer is the material of choice for lab on a chip consumable due to its cost-effectiveness and suitability for high volume production of disposables. Silicon and glass possess precise mechanical and chemical characteristics; however, they come with elevated production expenses and intricate processing procedures, especially when it comes to disposable devices. Polymers, on the other hand, can be conveniently produced using soft lithography or hot embossing techniques. In this process, a single mold can be used as a pattern for multiple devices [39]. It is better to use these procedures on high-volume disposable devices. However, surface modification is an essential step for trustworthy device performance because polymer mechanical and chemical properties are not as reliable. Recent advancements in surface treatments have primarily concentrated on polymeric materials. Despite the continued use of costly silicon or glass chips by some researchers, a significant effort is being made to develop reliable polymeric devices.

The most commonly used polymers are PDMA (polydimethylsiloxane), acrylic, polyester, polycarbonate, polystyrene, COC (cyclic olefin copolymer) and PMMA (polymethylmethacrylate) [40,41]. The polymers exhibit optical transparency, chemical inertness, resistance to various chemicals, high biocompatibility, flexibility, elastomeric properties, gas permeability, ease of molding and patterning, affordability, and widespread availability. However, PDMS shows severe limitations for industrial production, such as being incompatible with high-throughput chip fabrication procedures such as hot embossing or injection molding, also discussed in microfabrication methods. Paoli [42] emphasized that despite being slightly more challenging and costlier to utilize compared to PDMS, PMMAs present themselves as excellent options for creating lab-on-a-chip devices due to their strong mechanical properties, ease of machining, laser-cutting, or molding, decent thermal stability, and higher chemical inertness when compared to PDMS.

Paper

1. Whiteside, a renowned microfluidic researcher, provides support for the development of lab-on-a-chip devices using paper technologies, which yield significant advantages in applications that demand minimal expenses [43]. Paper is a substance composed of cellulose that has recently got attention as a potential substrate for the creation of inexpensive, biocompatible, flexible, and disposable microfluidic systems. Pranjal Chandra, from the Indian Institute of Technology, highlights the distinct characteristics of paper and plastic substrates, which include their durability, flexibility, mobility, cost-effectiveness, and straightforward manufacturing process [44]. Paper-based microfluidic systems have primarily been designed for diagnostic applications due to their properties, as the white background offers a suitable distinction for color-based finding procedures [45]. An increasing number of research studies are dedicated to the advancement of innovative paper-based lab-on-a-chip platforms. For instance, the combination of a paper-based lab-on-a-chip device with immunoassay techniques enables the identification of medically relevant levels of metabolites in urine samples [46].

MICROFABRICATION TECHNOLOGY

Franssila [47] explained that microfabrication encompasses a range of methodologies employed to fabricate miniature structures on the micro- and nanoscale, typically spanning from a few nanometers to several hundred micrometers. Microfabrication is of utmost importance in the advancement of Lab-on-a-Chip (LOC) devices, as it enables the creation of intricate microfluidic channels that are responsible for the manipulation and analysis of fluids. The design and manufacture of these tiny devices, which necessitate careful consideration of numerous elements, including biomaterials, microfluidics, and fabrication processes, is a crucial component of LOC technology. Lab-on-chip fabrication methods bear resemblance to those employed in microelectronics, as they both rely on closely associated microfabrication and integration techniques [48]. Microfluidics engineers have devised a range of approaches for fabricating submillimeter channels., including photolithography [49], soft lithography [50], stereolithography [51], laser micromachining [52], injection molding [53], hot embossing [54], 3D printing [55] and wet and dry etching [56]. The microelectronics sector is the source of numerous microfabrication processes. In this article, we reviewed the most common fabrication methods due to their versatility, precision, and suitability for creating the detailed and precise microstructures required in LOC devices. Micropatterning in microfluidics refers to the specialized methods utilized in the production of most devices. This process involves the integration of photolithography and soft-lithography, two lithography techniques, for creating substrate materials.

Photolithography

One important procedure for making microfluidic channels is photolithography, sometimes referred to as optical lithography. It used light to shift a pattern onto a substrate, usually a silicon wafer. Nishimura [57] detailed that the procedure commences with the application of a photosensitive material, known as a photoresist, onto the substrate through a technique called spin coating. A photoresist is a crucial material that is sensitive to light. It is applied as a coating on a substrate and plays a vital role in defining complex microstructures, including microfluidic channels, wells, and various other components on the substrate. Zhang [58] described that the photoresist is then covered with a photomask that holds the intended pattern. UV light is utilized in the most commonly employed photolithography technique to transfer a particular pattern from a photomask onto a rigid substrate covered with UV light-sensitive photoresist [59]. UV light is directed through the photomask in order to illuminate specific regions of the photoresist, thereby activating it in a selective manner. The uncovered regions experience a chemical transformation, causing them to become either soluble or insoluble in a developer solution. Following the development process, the design is then shifted onto the substrate using wet and dry etching techniques. The patterned substrate, which now functions as the master mold, is obtained by removing the remaining photoresist. The classification of this process depends on the type of light utilized, namely UV lithography and X-ray lithography [60]. This microfabrication technique is widely utilized due to its ability to generate highly detailed patterns, reaching sizes as small as a few nanometers. It offers accurate manipulation of object shapes and sizes. Moreover, it can produce patterns across a whole wafer in a swift and cost-effective manner. It is also applicable to a diverse range of substrates, such as silicon, glass, and polymers, and is compatible with an extensive array of materials utilized in microfabrication. Photolithography is limited in its ability to create masks on non-flat surfaces, despite its high-resolution capabilities. Qin [61] noted that this method necessitates the use of specialized equipment and cleanroom facilities, unlike soft lithography.

Soft lithography

Soft lithography, also referred to as replica molding, encompasses a series of methods employed for generating micro- and nanoscale patterns and structures on a substrate through the utilization of elastomeric stamps, molds, or masks. The term "soft" is attributed to the use of elastomer materials, with polydimethylsiloxane being a prominent example [62]. During this process, the patterned substrate (master mold) produced through photolithography is positioned within a mold casting arrangement. A liquid elastomer, usually polydimethylsiloxane (PDMS), is poured onto the master mold. The PDMS is solidified through the application of heat, enabling it to harden while preserving the precise features of the original mold's design. After being cured, the PDMS layer is carefully isolated from the master mold. Shao [63] observed that this PDMS layer serves as a negative replica of the pattern on the master mold. The PDMS replica, now bearing the imprinted microstructures, can serve as a functional element in diverse applications, including microfluidic channels within lab-on-a-chip devices. Numerous benefits of this patterning technique include low prices, fast throughput, simplicity of setup, and superb pattern precision. Although it is a flexible and popular method, especially for LOC devices, it is not as precise as more sophisticated photolithographic methods. Elastomeric stamps, particularly those fabricated from PDMS, may deteriorate with frequent utilization [64]. Conversely, in order to attain patterns of superior quality, soft lithography procedures require execution within cleanroom settings to mitigate the risk of contamination arising from dust and other particles. This requirement contributes to the overall expenses and intricacy associated with the process (Figure 3).

APPLICATIONS

Lab-on-a-Chip (LOC) technology allows lab procedures to be miniaturized on a microfluidic chip, which has transformed biomedical research and diagnostics. Lab-on-a-chip (LoC) technology has the ability to greatly enhance biomedical applications by providing low-cost, high-throughput, simple processes, and evaluation due to its miniaturization. This technology has been used for diagnosing various lethal diseases, including Chronic Respiratory Diseases (CRD), diabetes, Chronic Obstructive Pulmonary Disease (COPD) [65], neurological disorders [66], cardiovascular diseases [67], sickle cell anemia [68], cancer [69] and point-of-care diagnostics [70]. Finding techniques for the early stage diagnosis of fatal and chronic diseases is made easier with the use of LOCs. These devices provide numerous benefits, including decreased sample size requirements, accelerated analysis duration, and heightened sensitivity. A recent review published in the esteemed journal Nature highlights the transformative potential of LOC technology in revolutionizing healthcare [71]. By facilitating affordable and easily accessible diagnostics, this technology holds great promise in the field of chronic disease diagnosis.

Over 500 million people worldwide suffer from chronic respiratory disorders (CRDs), comprising asthma and chronic obstructive pulmonary disease (COPD) [72]. Traditional methods for diagnosing CRDs include spirometry, chest radiography, and biomarker analysis, such as eosinophil count and exhaled nitric oxide measurement. These techniques do, however, have drawbacks, such as low sensitivity and specificity and the frequent need for invasive operations. Lab-on-a-Chip (LOC) technology presents a hopeful resolution for diagnosing CRDs by facilitating the swift and precise identification of biomarkers, including inflammatory cytokines and lung function parameters. Cytokines, proteins, DNA, RNA, and volatile organic compounds (VOCs) are among the biomarkers that can be found in breath, blood, or sputum samples [73,74]. LOC devices have the capability to identify genetic predispositions to CRDs by analyzing patient DNA and utilizing techniques such as Polymerase Chain Reaction (PCR) and microarrays for rapid genetic analysis. The Nano Artificial Nose (NA-NOSE) is a lab-on-a-chip device designed to identify volatile organic chemicals (VOCs) present in exhaled air, serving as indicators for lung cancer [75].

Ferlay [76] reported that cancer is a leading factor in global mortality, resulting in around 10 million deaths associated with it in the year 2020. Traditional methods for cancer diagnosis typically involve techniques like biopsies, blood work, imaging tests (such as CT and MRI scans), and tumor marker analysis [77]. Imaging tests have the capability to detect small lesions or early-stage malignancies, but they are unable to provide the anatomical specifics of tumors. Lab-on-a-Chip (LOC) technology presents a potential option for cancer diagnosis by facilitating the identification of biomarkers like circulating tumor cells, DNA, microRNA, cancer-related proteins (such as PSA for prostate cancer), and genetic mutations (such as EGFR mutations in lung cancer) quickly and with high sensitivity [78]. High sensitivity, quick analysis times, little sample volume processing, early cancer identification, and treatment response tracking, are some benefits of LOC systems. The "CTC-Chip," a Lab-on-a-Chip (LOC) device, was made to identify circulating tumor cells (CTCs) in the blood of cancer patients [79].

Worldwide, diabetes affects more than 463 million individuals as a chronic illness, requiring timely diagnosis and monitoring to prevent complications [80]. The conventional approach to diagnosing diabetes requires multiple visits to the lab for processing and conducting fasting glucose tests and HbA1c readings. However, Lab-on-a-Chip (LOC) technology has transformed this process by enabling rapid on-site testing of small samples for glucose, insulin, HbA1c, and ketones [81]. Real-time data from LOC devices allows for immediate therapeutic changes. They increase portability and reduce costs, which enhances diabetes management's accessibility and effectiveness, particularly in rural areas. Lab-on-a-Chip (LOC) technology presents an optimistic resolution for the diagnosis of diabetes by facilitating the swift, sensitive, and minimally invasive detection of glucose, HbA1c, and other biomarkers.

Traditional techniques used to diagnose heart diseases encompass electrocardiograms (ECGs), echocardiograms, stress tests, and blood tests like troponin assays. However, these methods have certain drawbacks, including limited sensitivity and specificity, and frequently necessitate invasive procedures. Nazir and Iqbal [82] highlighted that with the ability to quickly and sensitively identify biomarkers like cardiac troponin, creatine kinase-MB, and brain natriuretic peptide, lab-on-a-chip (LOC) technology presents a promising option for the diagnosis of heart disorders. The field of neurological disorders is experiencing a transformation in the way neurological illnesses are diagnosed, thanks to Lab-on-a-Chip (LOC) technology. This innovative technology allows for the rapid and accurate detection of biomarkers. Cerebrospinal fluid (CSF) and blood samples can be examined using microfluidic-based devices to detect disease-specific biomarkers, such as proteins (e.g., amyloid-beta in Alzheimer's disease), genetic markers (e.g., mutations in Parkinson's disease), and neurotransmitters [83]. LOC systems offer precise and highly sensitive measurements that are crucial for monitoring disease progression and facilitating early detection.

Tebbi [84] reported that over 300,000 babies worldwide are born with sickle cell anemia, a hereditary condition that results in anemia, organ damage, and sickling of red blood cells. Conventional techniques used to diagnose sickle cell anemia consist of hemoglobin electrophoresis, high-performance liquid chromatography (HPLC), and polymerase chain reaction (PCR) tests. These ways are frequently invasive, time-consuming, and demand specialized equipment. Akther [89] discussed that LOC devices can be used for rapid blood analysis, potentially including tests to identify genetic abnormalities like those causing sickle cell disease. These miniaturized devices have the ability to expedite and increase the convenience of screening for the condition, especially in settings with limited resources.

EMERGING TRENDS

Pattanayak [18] described that Organ-on-a-Chip is a 3D in vitro tissue model that is micro-engineered, featuring interconnected micro-compartments through various microfluidic channels, devised to mimic the environment of the human body. OoCs refer to systems that consist of engineered or natural miniature tissues cultivated within microfluidic chips. These systems apply microfluidics and cells to replicate the physiological and mechanical conditions encountered within the human body. Lee [86] noted that hydrogels composed of natural substances like collagen have been employed in organ-on-a-chip systems to ease cellular organization. Soft lithography and BioMEMS (BioMicroElectroMechanical Systems) are used in the device's manufacturing process to enable the correct production of the microscale details. Ma [87] highlighted that the objective of organ-on-a-chip technology is to produce human tissue models that can be employed for disease modeling and drug testing objectives [9-17,87]. Table 2 provides an in-depth look at the applications, key considerations and recent advancements in Organ-on-a-Chip technology.

CHALLENGES

The majority of lab-on-a-chip technologies are still not prepared for industrial-scale production [88]. Schoenitz [89] observed that tiny channels are susceptible to blockages from impurities or air bubbles, hindering fluid flow and experiment results. Mixing fluids efficiently within microchannels can be challenging, affecting reaction rates and assay accuracy. Manufacturing scalable lab on chip devices at a reasonable cost is a technical challenge. Not all materials are suitable for microfabrication or function well at the microscale. The complex processes involved in microfabrication can make LOC devices expensive to produce, limiting their widespread use. Miniaturization can lead to an amplified signal/noise ratio in certain applications, causing lab-on-a-chip to yield inferior outcomes compared to traditional methods [90]. Without regulations, the extensive accessibility of lab-on-a-chip may cause fears about its use as a diagnostic tool by the untrained public at home. Despite their small size and impressive capabilities, lab-on-a-chip devices require the use of specialized equipment like electronics or flow control systems in order to function effectively [91]. While OoC devices can mimic certain aspects of human organs, they cannot fully replicate the complexity of human physiology. What strategies can be employed to overcome the limitations and enhance the robustness of LOC systems?

FUTURE DIRECTIONS

Numerous studies are currently underway to enhance the usability of lab-on-a-chip devices. Microfluidics will increasingly integrate with digital platforms for real-time data analysis and remote monitoring, enhancing usability and functionality. Lab-on-a-chip integrating smartphones for cholesterol testing, anemia diagnosis, cardiovascular disease monitoring, or Elisa assays [92,93]. Combining LOCs with microarrays, biosensors, and other miniaturized tools will create powerful lab analysis platforms. The integration of nanofabrication techniques will allow for the creation of features at the nanoscale, leading to enhanced sensitivity and functionality in LOC devices [94]. LOCs can be used to analyze individual patient samples for personalized treatment strategies [95]. The demand for lab-on-a-chip testing in clinical diagnosis is on the rise, and numerous devices have been made available for important applications like glucose monitoring, HIV detection, and heart attack diagnostics [96]. By integrating advancements in tissue engineering and microfabrication, Organ-on-a-Chip (OoC) systems have gained attention as a cutting-edge experimental tool for studying human pathophysiology and evaluating the impact of therapeutic involvements within the body [97]. AI-powered analysis of data generated by LOC devices will enable faster and more accurate diagnoses. Disc-shaped LOC platforms offer potential advantages in terms of scalability and functionality compared to conventional chip designs [98].

CONCLUSION

In conclusion, Lab-on-a-Chip (LOC) technology has emerged as a groundbreaking innovation in the realm of microfluidics, offering immense potential across various fields such as clinical diagnostics and biochemical analysis. The fundamental principles of microfluidics enable the precise manipulation of fluids at a microscale, leveraging materials such as silicon, glass, and polymers like PDMS for diverse applications. Advanced microfabrication techniques, including photolithography and soft lithography, have paved the way for the creation of intricate LOC devices with high precision and reproducibility. Lab-on-a-Chip (LOC) technology offers transformative potential for diagnosing chronic diseases by enabling rapid, accurate, and minimally invasive testing. Continued advancements in LOC technology promise to enhance early detection and personalized treatment, ultimately improving patient outcomes and reducing healthcare costs. Despite these promising applications, LOC technology faces several challenges that hinder its widespread adoption. These include issues related to the scalability of manufacturing processes, material limitations, and the integration of complex functionalities within a single chip. Furthermore, the commercialization of LOC devices is often constrained by regulatory hurdles and the need for standardization. Looking ahead, emerging trends such as the incorporation of nanomaterials, OoC, disc-shaped LOC, and the development of biocompatible materials hold promise for overcoming current limitations. Continued research and innovation will undoubtedly drive the evolution of this technology, making it an integral part of future scientific advancements.

AUTHOR CONTRIBUTION STATEMENT

MA: Conceptualization, writing original draft, Draw Figures. SAI and MM: Writing, Review and Editing. MM and SA:  Data collection & curation, making Tables.

CONFLICT OF INTEREST

The authors declare no conflict of interest.

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  Table 1
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  Table 2