Meeting all of these requirements can be a challenge. Detecting low concentration targets in small sample volumes is particularly tricky, as is managing specific versus non-specific binding in complex sample environments. Even surface coatings and receptor alignments, designed to keep things orderly, are vulnerable to changes in temperature, pH, and other environmental conditions. As a result, developing reliable, miniaturized diagnostics often remains just out of reach.1 Microfluidics could be a way forward.
An Overview of Microfluidics
Microfluidics is the science of manipulating tiny fluid volumes (10-9 to 10-18 liters) within micro-scale channels, enabling accurate control over molecular concentrations in space and time. Microfluidic systems are cheap to run, require vanishingly small volumes of reagents, and allow exquisite control over reaction conditions.
When designing systems, poly-dimethylsiloxane (PDMS) is the most commonly used fabrication material because of its optical transparency and compatibility with microfluidic components like pneumatic valves. Recently, paper- and cloth-based microfluidics gained attention for their low cost, lightweight, and ease of fabrication, which makes them suitable for point-of-care (POC) applications. Major features include minimal liquid consumption and compact structure size.1
Introduction to Microfluidic Biosensors
When biosensing is combined with microfluidics, the result is the so-called "lab-on-a-chip" devices. These devices merge fluid handling, detection, and signal processing in a super-compact form. Within their microchannels, fluids flow smoothly in predictable patterns, reagents are used sparingly, and heat disperses efficiently.2,3
Looking further into the biosensing side, advances in chemistry, optics, and electronics mean that biological interactions can be translated into electrical, acoustic, magnetic, or even optical signals with increasing sensitivity. Many biosensors enable label-free detection, amplifying weak signals while simplifying processes and reducing interference, making them crucial for compact, efficient diagnostic systems.2,3
Together, these technologies create a compact system capable of executing the entire diagnostic workflow, sample preparation, separation, reaction, and cleaning on a single chip. Microfluidic biosensors capture and process biological signals in real time, translating them into quantifiable results. This integration allows a seamless sample-to-result diagnostic platform, supporting the efficient and cost effective analysis required in biomedical and clinical applications.2-4
Advantages of Microfluidic Biosensors
Microfluidic biosensors integrate sensing elements into microfluidic chips, automating sample handling and analysis. These systems combine the advantages of both technologies into a single, compact format.
The microfluidic "lab-on-a-chip" devices miniaturize laboratory processes, guiding tiny fluid volumes through channels where laminar flow dominates. This setup reduces reagent consumption, lowers costs, and improves efficiency. The biosensing aspect converts these labflows to signals, measured with high sensitivity. Many microfluidic biosensing systems are label-free, amplify weak signals while reducing interference, and simplify workflows.1
By tightly controlling flow rates, channel dimensions, and reaction times, these sensors accelerate assays, shorten diffusion distances, and ensure an even distribution of target molecules.
Automation is another major advantage, allowing integration of sample handling, sensing, surface modification, and environmental control. Although achieving complete automation remains challenging due to the complexity of biological samples, there are emerging studies that hope to evade these issues. For instance, lateral flow immunosensors for enzyme immunoassays (EIA) offer automated, step-free detection using delayed-release chemiluminescent substrates controlled by asymmetric polysulfone membranes.1
Microfluidic devices also reduce the sensing area, which both minimizes sample requirements and increases sensitivity; in some cases, they've been reported to improve sensitivity by up to 100-fold. Their closed, stable environments shield samples from external interference, improving reliability in portable or on-site testing. These qualities make them especially attractive for POC diagnostics.1
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Applications of Microfluidic Biosensors
Microfluidic biosensors are used in a diverse range of applications.2
Point of Care Testing
With rising rates of infectious, inflammatory, and chronic diseases, POCT has become a priority in healthcare. Microfluidic biosensors provide high sensitivity, low reagent consumption, and portability. However, challenges remain in ensuring accuracy, ease of use, and applicability in low-resource settings. These sensors are widely applied in diagnosing inflammation, infections, and chronic conditions.2
Researchers have developed a multitude of diagnostic tools for the rapid and sensitive detection of various clinical conditions. One study revealed the successful design of an aggregation-induced luminescent nanobead (AIENB)-based dual-readout lateral flow immunoassay (LFA) for detecting C-reactive protein (CRP). This AIENB-LFA, fabricated using an emulsification-solvent evaporation technique, achieved a visual detection limit of 8.0 mg/L and a fluorescence-based limit of detection (LOD) of 0.16 mg/L for high-sensitivity CRP (hs-CRP), performing comparably to immunoturbidimetric assays.2
Another group developed a portable micro-imaging system for at-home detection of vaginal inflammation. Using a self-absorbing microfluidic chip and a smartphone-adaptable optical system (37× magnification, four to six millimeter focus range), paired with a mobile app for cocci identification, the system showed high resolution, accuracy, and rapid detection in both simulated and clinical samples.2
Similarly, a portable microchip liquid chromatography (LC) system was developed for rapid glycated hemoglobin (HbA1c) detection. Integrating a micromixer, injector, packed column, and detection unit, the sensor accurately separated four HbA1c levels in under two minutes, with <3.2 % inaccuracy and a correlation coefficient of 0.993. It shows a successful, rapid, and reliable tool for diabetes diagnosis.2
Cancer Liquid Biopsy
Microfluidic platforms have transformed liquid biopsy, a minimally invasive tool for cancer diagnosis and monitoring. Advances include bilayer chips equipped with antibody-coupled magnetic nano/microgels for capturing circulating tumor cells with high efficiency, and surface-enhanced Raman spectroscopy chips capable of detecting circulating tumor DNA at attomolar sensitivity in 13 minutes.2
Pathogenic Bacteria Assessment
They have also been transformative in pathogenic bacteria detection. Using biorecognition strategies, like antibody-antigen interactions, nucleic acid aptamer binding, phage-based recognition, and antimicrobial peptide targeting. They offer superior selectivity and accuracy compared to conventional methods, allowing for the specific identification of pathogens even within complex biological samples. Additionally, these biosensors enable efficient purification and detection of viable bacterial cells.2
One approach involved using immunomagnetic beads (IMBs) combined with antibody-functionalized europium fluorescent-labeled particles to detect Vibrio parahaemolyticus. This method successfully trapped the bacteria via antibody-antigen binding and provided quantifiable fluorescence signals, enabling precise detection at the single-cell level in just 0.1 mL of broth culture.
Another technique used an optically induced dielectric electrophoresis (ODEP)-based microfluidic device to isolate live bacteria directly from blood. Initially, blood cells are removed using IMB-based separation. Then, ODEP technology, guided by a dynamic photoimage array, directs blood cells away while collecting bacteria. This method achieved bacterial purity levels between 90.5 % and 99.2 % in studies, with no detrimental effects on the function of surrounding cells.2
Conclusion
Microfluidics is an incredibly influential technology in biosensing. Combining sensitivity and specificity with automation and low sample requirements makes them powerful tools in healthcare.
With further development, microfluidic biosensors could become indispensable for rapid and reliable diagnostic care.
References and Further Reading
- Wang, J., Ren, Y., Zhang, B. (2020). Application of microfluidics in biosensors. IntechOpen. DOI:10.5772/intechopen.91929, https://www.intechopen.com/chapters/71835
- Wang, S., Guan, X., Sun, S. (2025). Microfluidic Biosensors: Enabling Advanced Disease Detection. Sensors, 25(6), 1936. DOI:10.3390/s25061936, https://www.mdpi.com/1424-8220/25/6/1936
- Kulkarni, M. B., Ayachit, N. H., & Aminabhavi, T. M. (2022). Biosensors and Microfluidic Biosensors: From Fabrication to Application. Biosensors, 12(7), 543. DOI:10.3390/bios12070543, https://www.mdpi.com/2079-6374/12/7/543
- Siavashy, S., Soltani, M., Rahimi, S., Hosseinali, M., Guilandokht, Z., Raahemifar, K. (2024). Recent advancements in microfluidic-based biosensors for detection of genes and proteins: Applications and techniques. Biosensors and Bioelectronics: X, 19, 100489. DOI: 10.1016/j.biosx.2024.100489, https://www.sciencedirect.com/science/article/pii/S2590137024000530
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