Microfluidics is a flourishing field, enabling a wide range of biochemical and clinical applications such as cancer screening, micro-physiological system engineering, high-throughput drug testing, and point-of-care diagnostics. However, fabrication of microfluidic devices is often complicated, time consuming, and requires expensive equipment and sophisticated cleanroom facilities. Three-dimensional (3D) printing presents a promising alternative to traditional techniques such as lithography and PDMS-glass bonding, not only by enabling rapid design iterations in the development stage, but also by reducing the costs associated with institutional infrastructure, equipment installation, maintenance, and physical space. With the recent advancements in 3D printing technologies, highly complex microfluidic devices can be fabricated via single-step, rapid, and cost-effective protocols, making microfluidics more accessible to users. In this review, we discuss a broad range of approaches for the application of 3D printing technology to fabrication of micro-scale lab-on-a-chip devices.

A transformation of the healthcare industry is necessary and imminent: hospital-centered, reactive care will soon give way to proactive, person-centered care which focuses on individuals' well-being. However, this transition will only be made possible through scientific innovation. Next-generation technologies will be the key to developing affordable and accessible care, while also lowering the costs of healthcare. A promising solution to this challenge is low-cost continuous health monitoring; this approach allows for effective screening, analysis, and diagnosis and facilitates proactive medical intervention. Urine has great promise for being a key resource for health monitoring; unlike blood, it can be collected effortlessly on a daily basis without pain or the need for special equipment. Unfortunately, the commercial rapid urine analysis tests that exist today can only go so far-this is where the promise of microfluidic devices lies. Microfluidic devices have a proven record of being effective analytical devices, capable of controlling the flow of fluid samples, containing reaction and detection zones, and displaying results, all within a compact footprint. Moving past traditional glass- and polymer-based microfluidics, paper-based microfluidic devices possess the same diagnostic ability, with the added benefits of facile manufacturing, low-cost implementation, and disposability. Hence, we review the recent progress in the application of paper-based microfluidics to urine analysis as a solution to providing continuous health monitoring for proactive care. First, we present important considerations for point-of-care diagnostic devices. We then discuss what urine is and how paper functions as the substrate for urine analysis. Next, we cover the current commercial rapid tests that exist and thereby demonstrate where paper-based microfluidic urine analysis devices may fit into the commercial market in the future. Afterward, we discuss various fabrication techniques that have been recently developed for paper-based microfluidic devices. Transitioning from fabrication to implementation, we present some of the clinically implemented urine assays and their importance in healthcare and clinical diagnosis, with a focus on paper-based microfluidic assays. We then conclude by providing an overview of select biomarker research tailored towards urine diagnostics. This review will demonstrate the applicability of paper-based assays for urine analysis and where they may fit into the commercial healthcare market.

Paper-based micro analytical devices offer significant advantages compared to the conventional microfluidic chips including cost-effectiveness, ease of fabrication, and ease of use while preserving critical features including strong capillary action and biological compatibility. In this work, we demonstrate an inexpensive, rapid method for high-throughput fabrication of paper-based microfluidics by patterning hydrophobic barriers using a desktop pen plotter integrated with a custom-made, low-cost paper feeder. We tested various types of commercial permanent markers and compared their water-resistant capabilities for creating hydrophobic barriers. Additionally, we studied the performance of markers with different types of paper, plotting speeds, and pattern dimensions. To verify the effectiveness of the presented fabrication method, colorimetric analysis was performed on the results of a glucose assay.

There is an unmet need for high-throughput fabrication techniques for paper-based microanalytical devices, especially in limited resource areas. Fabrication of these devices requires precise and repeatable deposition of hydrophobic materials in a defined pattern to delineate the hydrophilic reaction zones. In this study, we demonstrated a cost- and time-effective method for high-throughput, easily accessible fabrication of paper-based microfluidics using a desktop pen plotter integrated with a custom-designed multipen holder. This approach enabled simultaneous printing with multiple printing heads and, thus, multiplexed fabrication. Moreover, we proposed an ink supply system connected to commercial technical pens to allow continuous flow of the ink, thereby increasing the printing capacity of the system. We tested the use of either hot- or cold-laminating layers to improve (i) the durability, stability, and mechanical strength of the paper-based devices and (ii) the seal on the back face of the chromatography paper to prevent wetting of the sample beyond the hydrophilic testing region. To demonstrate a potential application of the paper-based microfluidic devices fabricated by the proposed method, colorimetric urine assays were implemented and tested: nitrite, urobilinogen, protein, blood, and pH.

No abstract