Chip-based electrochemical platforms typically use planar interdigitated microelectrode ("P-IDμE"). However, P-IDμE suffers from a limited electric field penetration, limiting its sensitivity and selectivity for sensor usage. Hence researchers have devised novel methods to increase the field penetration for P-IDμE, including (i) inclusion of nanomaterials to increase the active electrode surface area or (ii) design elaborated device structure. A simple yet elegant method to fabricate a microfluidic electrochemical sensor based on the P-IDμE architecture for ultrasensitive detection remains a challenge.Our lab has devised a novel three-dimensional (3D) electrode architecture, as shown in Figure 1. Our method to fabricate this 3D electrode is simple and convenient. Our 3D electrode architecture consists of three layers: the top and bottom glass layers decorated with platinum (Pt) or gold (Au) μEs, and a middle microfluidic channel layer of double-sided polypropylene tape. The tape layer with desired channel pattern is sandwiched by nonplanar interdigitated microelectrodes ("NP-IDμE"). The use of polypropylene tape allows NP-IDμE to have a 3D electrode structure without extensive and costly fabrication steps. Further, the polypropylene middle layer provides the advantages of (i) A reasonably wide operating temperature window (−40°C to 120°C). (ii) Fast and easy electrode assembly. (iii) Excellent reagent-resist properties.Interestingly the 3D electrode architecture of NP-IDμE leads to some sustained electrochemical advantages over conventional P-IDμE besides the improved electric field penetration. A finite element analysis (FEA) simulation using COMSOL Multiphysics was undertaken to observe the enhanced field penetration in NP-IDμE, as demonstrated in Figure 1. Further, in P-IDμE’s, the electrode process is predominated by radial diffusion process, while in NP-IDμE, the diffusion is linear semi-infinite process. This change in the diffusion allows NP-IDμE to extract more significant insight into the analyte's electron transfer mechanism.Moreover, as the μE arrays are nonplanar, it allows us to observe the effect of the inderdigitization of the electrodes. It is observed experimentally that only when the electrodes in NP-IDμE are interdigitated, one observes a well-defined cyclic voltammetry (CV) and differential pulse voltammetry (DPV) profiles. We attribute this to the weakening of the electromigration term from the increased separation between the μE pairs. This was validated by electrochemical impedance spectroscopy (EIS). In EIS, we see a substantial increase in the charge transfer resistance as the μE arrays are further and further apart. As the electrodes are not modified, and the electrolyte conductivity is unchanged, this phenomenon is driven by the decrease in the electromigration term between the electrodes.NP-IDμE was further evolved to make a quasi 4D electrode. Room temperature, operator-independent, instrumentation less fabrication protocol for NP-IDμE allows us to pack NP-IDμE with different dielectric materials like metal organic framework (MOF) materials or conducting materials like carbon nanotubes (CNTs). This allows us to change the electrode response of NP-IDμE substantially. One example of such response is from packing MOFs in the channel. Nanoporous MOFs are loaded into the fluid channel and sandwiched between μE layers. This MOFs-based-NP-IDμE configuration adapted in this work provides the following sensor advantages. (i) Shear force enhanced: For our flow-based NP-IDμE microfluidic device, the introduction of nanoporous MOFs allows us to tremendously increase the shear force in the device, improving the selectivity and hence reducing false positives. (ii) Convective transport: The packing of the channel leads to a substantial increase in the convective transport in the NP-IDμE device. This enhances mixing, allowing more collisions between the capture sites in the MOF and the target analyte, leading to increased sensitivity. Further, the convective transport removes any diffusional limitations, which pushes the double layer relaxation time to high frequency. This allows us to measure the charge transfer resistance at high frequency, allowing for increased signal to noise and high sensitivity, thus lowering false negatives. Figure 1