(638f) Democratizing Microfluidic Innovation and Commercialization Using Microfluidic Pressure in Paper (µPiP) for Scalable Ultra-Low Cost Manufacturing

Microfluidic engineering has received widespread attention due to the great promise for miniaturizing robust and portable micro total analysis systems (μTAS, or lab-on-a-chip) across a wide range of industries and applications, including point-of-care diagnostics, environmental and public health monitoring, and the detection of biowarfare agents. However, despite significant engineering innovations over the last two decades, market penetration and commercial adoption of microfluidic devices in our daily life remains very low. We believe one reason for this is a lack in a low-cost manufacturing method for producing microfluidic chips. While techniques such as injection molding and laser ablation are capable of scalable production, they can require a six-figure financial investment for both the development and the production phases of commercialization. Such a lack of rapid, scalable fabrication techniques at low-cost is therefore a major bottleneck for enabling innovation and market penetration for researchers who lack access to these expensive methods. Therefore, a low-cost, scalable, robust and reproducible microfluidic device manufacturing method will have significant impact in democratizing innovation, and for allowing stakeholders in both academia and industry to rapidly translate and commercialize microfluidic systems without requiring significant financial investment.

Here, we report a novel low-cost method for scalable manufacturing of microfluidic devices using a combination of precision cut paper and thin PDMS membranes. We call this technique “Microfluidic Pressure in Paper” (µPiP). In µPiP, we utilize a CO₂ laser to rapidly cut hundreds of paper fluidic channels at microscale resolution. We then confine these paper channels between two thin PDMS sheets. Using a combination of corona plasma treatment and high pressure (~5.5 MPa) thermal press, we confine and chemically seal these paper channels within the PDMS membranes. Using this novel workflow, the final µPiP devices are tightly sealed within the PDMS and are void of any air bubbles or structural deformation. We then use a low-cost pressure system to drive fluid through the paper channels in the same way that flows are driven within conventional commercial injection molded chips. Our method, however, can produce hundred-thousands of devices per day for less than a $25,000 USD initial investment and does not require a clean-room. We investigate the fluidic characteristics of these devices using a combination of porous-flow mathematical models for pressure driven fluid flow through polymer-confined paper channels and microfluidic experiments. We demonstrate that, unlike conventional paper-based devices, the hydraulic characteristics of these µPiP devices are not influenced by evaporation or the surrounding relative humidity. We then demonstrate the applicability of µPiP with a range of aqueous buffers and biological samples, including human whole blood. In addition, we demonstrate a wide variety of successful µPiP use cases, including a paper-based microfluidic gradient generator, an H-filter, and a red blood cell deformability assay. We also demonstrate sample preparation operations using µPiP. Finally, we show how to use µPiP to produce conventional PDMS channels using water soluble paper as a sacrificial channel structure. To the best of our knowledge, this is the first time an external flow system has been used to actively drive microfluidic flow through paper-based channels. Our novel fabrication technique democratizes microfluidic innovation by significantly reducing fabrication costs and enables the manufacturing robust microfluidic devices at scale using a workflow that any researcher, regardless of funding, can successfully utilize.