Coffee-ring effect presents in many natural phenomena, and the ubiquitous nature of this physical impact makes it difficult to circumvent. Depending on the application, coffee-ring can be a detrimental or beneficial effect. This research is aimed at scrutinizing a multidisciplinary study on the underlying physics behind this effect for controlling or taking advantage of it. To be more specific, understanding the reasons causing this phenomenon, I theoretically and experimentally investigate the non-invasive ways to suppress ring-like particles’ deposition, applicable for ultrasensitive platforms, such as electrochemical sensors. On the other hand, I use the coffee-ring effect to increase the sensitivity of nano-biosensors, expedite detection, and enhance the diagnosis and prognosis of diseases.In the first part of this thesis, a non-intrusive meniscus-free and coffee-ring-free method, inspired by nature, is developed to form uniform particle films. When a saline lake evaporates, a uniform layer of salt deposits on the lake-bed due to a meniscus-free air-water interface. The deposition nature of the salt layer is emulated on a small scale by placing a particle-laden sessile droplet on an accurately designed shadow mold over a substrate, eliminating the radial particle migration. This method demonstrated forming of highly ordered monolayers and fabrication of self-organized multilayer constructs, customized patterns, nanoscale continuously variablesize filters, and highly reproducible functionalized electrodes for nano-biosensing. A theoretical model is also developed to simulate the effects of geometrical and physicochemical parameters involved in particle deposition. Enabling the repeatable generation of highly uniform layers makes this method a versatile approach for applications spanning from genotyping to molecular diagnosis.In the next part of the thesis, I incorporate the coffee-ring approach with the molecular pendulum (MP) electrochemical sensing method to develop a reagentless SARS-CoV-2 sensor with improved response time and sensitivity. To achieve this, the natural capillary flow, offered by the coffee ring effect, provides enhanced sensitivity without external manipulation, developing the first coffee ring-enabled reagentless sensor. Sensors are fabricated from preexisting screen-printed electrodes through laser removal of the electrode interior, resulting in uniform ring-shaped electrodes; electrode ring thickness and gold nanoneedles are carefully optimized to ensure maximum sensitivity. By incorporating the coffee ring effect with MPbased sensing, we achieve significantly enhanced sensitivity towards detecting both antigens and body of the target viruses, demonstrated with clinical SARS-CoV-2 samples. In addition to experimental results, a comprehensive theoretical study is conducted to verify and support the robustness of this coffee-ring preconcentration approach.Finally, in the last step of my thesis, I use a microfluidic-based electrochemical sensing approach to not only eliminate the coffee-ring effect by avoiding evaporation during fluid manipulation but also assist scalability and robustness of functionalizing sensors. In the absence of reliable methods for large-scale production of reproducible and repeatable nanomaterial morphologies on the electrodes, they are fabricated individually in batch production. This has become a significant challenge in the practical implementation of electrochemical nano-biosensors. To address this challenge, an automated microfluidic-based platform (NanoChip) is designed for the semi-scale production of reproducible complex nanomaterial structures with a defined order of nanocomposites and biomaterials to fabricate ultrasensitive nano-biosensors. In this regard, using an automated liquid handling system, the desired reagent is delivered to electrodes integrated temporarily into the chip for amending their surfaces by depositing different nanomaterials. The NanoChip platform is utilized to form a multilayer nanocomposite structure on the electrode surface. These reproducible nanobiosensors are then applied to detect breast cancer cells in the blood. The Performance of nanobiosensors produced by NanoChip demonstrates similar dynamic range and selectivity along with enhanced sensitivity and reproducibility compared to the sensors created utilizing the batch process. These factors make the designed NanoChip platform a versatile and reliable tool for fabricating ultrasensitive nano-sensors to monitor different markers in clinical, medical, and environmental applications.