Polydimethylsiloxane (PDMS) is a silicone-based synthetic material used in various biomedical applications due to its properties, including transparency, flexibility, permeability to gases, and ease of use. Though PDMS facilitates and assists the fabrication of complicated geometries at micro- and nano-scales, it does not optimally interact with cells for adherence and proliferation. Various strategies have been proposed to render PDMS to enhance cell attachment. The majority of these surface modification techniques have been offered for a static cell culture system. However, dynamic cell culture systems such as organ-on-a-chip devices are demanding platforms that recapitulate a living tissue microenvironment’s complexity. In organ-on-a-chip platforms, PDMS surfaces are usually coated by extracellular matrix (ECM) proteins, which occur as a result of a physical and weak bonding between PDMS and ECM proteins, and this binding can be degraded when it is exposed to shear stresses. This work reports static and dynamic coating methods to covalently bind collagen within a PDMS-based microfluidic device using polydopamine (PDA). These coating methods were evaluated using water contact angle measurement and atomic force microscopy (AFM) to optimize coating conditions. The biocompatibility of collagen-coated PDMS devices was assessed by culturing primary human bronchial epithelial cells (HBECs) in microfluidic devices. It was shown that both PDA coating methods could be used to bind collagen, thereby improving cell adhesion (approximately three times higher) without showing any discernible difference in cell attachment between these two methods. These results suggested that such a surface modification can help coat extracellular matrix protein onto PDMS-based microfluidic devices.

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Polydimethylsiloxane (PDMS) is a silicone-based synthetic material that is used in various biomedical applications due to its properties, including transparency, flexibility, permeability to gases, and ease of use. Though PDMS facilitates and realizes the fabrication of complicated geometries at the micro and nano scales, it does not optimally interact with cells for adherence and proliferation. Different strategies have been proposed to render PDMS to enhance cell attachment. The majority of these surface modification techniques have been offered for a static cell culture system. However, dynamic cell culture systems such as organ-on-a-chip devices are demanding platforms that recapitulate the complexity of a living tissue microenvironment. For organ-on-a-chip platforms, PDMS surfaces are usually coated by ECM proteins, which occur as a result of physical, weak bonding between PDMS and ECM proteins, and this binding can be degraded when it is exposed to shear stresses. This work reports static and dynamic coating methods to covalently bind collagen within a PDMS-based microfluidic device using polydopamine (PDA). These coating methods were evaluated using water contact angle measurement and atomic force microscopy (AFM) to find the optimum coating conditions. The biocompatibility of collagen-coated PDMS devices was assessed by culturing primary human bronchial epithelial cells (HBECs) in microfluidic devices. It was shown that both PDA coating methods could be used to bind collagen, thereby improving cell adhesion (around three times higher) without showing any discernible difference. These results suggested that such a surface modification can be used to coat an extracellular matrix protein onto PDMS-based microfluidic devices.

Hydrogels are a critical component of many microfluidic devices. They have been used in cell culture applications, biosensors, gradient generators, separation microdevices, micro-actuators, and microvalves. Various techniques have been utilized to integrate hydrogels into microfluidic devices such as flow confinement and gel photopolymerization. However, in these methods, hydrogels are typically introduced in post processing steps which add complexity, cost, and extensive fabrication steps to the integration process and can be prone to user induced variations. Here, we introduce an inexpensive method to locally integrate hydrogels into microfluidic devices during the fabrication process without the need for post-processing. In this method, porous and fibrous membranes such as electrospun membranes are used as scaffolds to hold gels and they are patterned using xurography. Hydrogels in various shapes as small as 200  μm can be patterned using this method in a scalable manner. The electrospun scaffold facilitates drying and reconstitution of these gels without loss of shape or leakage that is beneficial in a number of applications. Such reconstitution is not feasible using other hydrogel integration techniques. Therefore, this method is suitable for long time storage of hydrogels in devices which is useful in point-of-care (POC) devices. This hydrogel integration method was used to demonstrate gel electrophoretic concentration and quantification of short DNA (150 bp) with different concentrations in rehydrated agarose embedded in electrospun polycaprolactone (PCL) membrane. This can be developed further to create a POC device to quantify cell-free DNA, which is a prognostic biomarker for severe sepsis patients.

Microfluidic devices have been conventionally fabricated using traditional photolithography or through the use of soft lithography both of which require multiple complicated steps and a clean room setup. Xurography is an alternative rapid prototyping method which has been used to fabricate microfluidic devices in less than 20-30 minutes. The method is used to pattern two-dimensional pressure-sensitive adhesives, polymer sheets, and metal films using a cutting plotter and these layers are bonded together using methods including adhesive, thermal, and solvent bonding. This review discusses the working principle of xurography along with a critical analysis of parameters affecting the patterning process, various materials patterned using xurography, and their applications. Xurography can be used in the fabrication of microfluidic devices using four main approaches: making multiple layered devices, fabrication of micromolds, making masks, and integration of electrodes into microfluidic devices. We have also briefly discuss the bonding methods for assembling the two-dimensional patterned layers. Due to its simplicity and the ability to easily integrate multiple materials, Xurography is likely to grow in prominence as a method for fabrication of microfluidic devices.

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