Via-Holes for Integrated Microfluidics

High-throughput operation is one of the major objectives of microfluidics technology for biomedical applications [1]. Miniaturizing fluidic devices from microliters to picoliters in a multiplexed format has the potential to enable the parallel analysis of hundreds to thousands of biological samples while reducing reagent consumption. Microfluidic part fabrication based on soft lithography enables complicated and extremely compact device designs. In the fabrication process, the photolithography for mold fabrication and replica molding of polydimethylsiloxane (PDMS) using soft lithography is a standardized process for any arbitrary microfluidic channel network as a planar structure [2]. Building stacked layers through multilayer soft lithography principally relies on simple bonding of the molded layers, rather than the geometry of channel structures. Furthermore, the relative manufacturing efforts on a microfluidic chip line unit can be greatly reduced if a microfluidic chip is designed with a “unit” architecture, in which channel networks or valves can be operated in different configurations. Having flexible device architecture is particularly important for cell-based assays [3], which have relatively large undetermined variations and require multiple repeated experiments to statistically validate experimental hypotheses. With a well-designed channel layout, many of the solution inlets/outlets and valve control ports can be shared among multiple device elements. Through design optimization, the number of required fluidic connections can be minimized, reducing off-chip work that includes solution preparation and connecting input (flow and control) lines into the devices. The risk of chip failure increases with the number of inputs, providing a strong motivation to put additional effort into channel routing and multiplexing strategies instead of making chips by a brute force, trial and error approach. However, routing of microchannel networks, particularly for high density co-planar designs [3], is non-trivial and limits the arrangements of microfluidic elements (e.g. pumps and mixers [4]) within the same device. Considering the analogy between the channels in microfluidic devices and wires in electronics, the concept of routing using electrical via-holes in printed circuit boards (PCBs) [5] is a traditional but still interesting strategy that can potentially solve some of the layout problems encountered in planar microfluidic networks. Electrical via-holes are placed between two layers of circuit patterns in electrical printed circuit boards. In this work, we adopt a similar strategy to establish a fabrication process compatible with the multilayer soft lithography Received: December 16, 2019


Short Communication
High-throughput operation is one of the major objectives of microfluidics technology for biomedical applications [1].
Miniaturizing fluidic devices from microliters to picoliters in a multiplexed format has the potential to enable the parallel analysis of hundreds to thousands of biological samples while reducing reagent consumption. Microfluidic part fabrication based on soft lithography enables complicated and extremely compact device designs. In the fabrication process, the photolithography for mold fabrication and replica molding of polydimethylsiloxane (PDMS) using soft lithography is a standardized process for any arbitrary microfluidic channel network as a planar structure [2]. Building stacked layers through multilayer soft lithography principally relies on simple bonding of the molded layers, rather than the geometry of channel structures. Furthermore, the relative manufacturing efforts on a microfluidic chip line unit can be greatly reduced if a microfluidic chip is designed with a "unit" architecture, in which channel networks or valves can be operated in different configurations. Having flexible device architecture is particularly important for cell-based assays [3], which have relatively large undetermined variations and require multiple repeated experiments to statistically validate experimental hypotheses.
With a well-designed channel layout, many of the solution inlets/outlets and valve control ports can be shared among multiple device elements. Through design optimization, the number of required fluidic connections can be minimized, reducing off-chip work that includes solution preparation and connecting input (flow and control) lines into the devices. The risk of chip failure increases with the number of inputs, providing a strong motivation to put additional effort into channel routing and multiplexing strategies instead of making chips by a brute force, trial and error approach. However, routing of microchannel networks, particularly for high density co-planar designs [3], is non-trivial and limits the arrangements of microfluidic elements (e.g. pumps and mixers [4]) within the same device. Considering the analogy between the channels in microfluidic devices and wires in electronics, the concept of routing using electrical via-holes in printed circuit boards (PCBs) [5] is a traditional but still interesting strategy that can potentially solve some of the layout problems encountered in planar microfluidic networks. Electrical via-holes are placed between two layers of circuit patterns in electrical printed circuit boards. In this work, we adopt a similar strategy to establish a fabrication process compatible with the multilayer soft lithography

ARTICLE INFO Abstract
Integrated microfluidics has been well demonstrated as an irreplaceable advanced technology with abundant biomedical applications. Nevertheless, layout design of the microfluidic device can be challenging; and sometimes it can have limitations on connections among different microfluidic elements (e.g. pumps, chambers and mixers), especially for the highly integrated designs. Here, we present the design and fabrication of microfluidic via-holes, which offer fluidic connections between different microchannel layers. Analogous to the electrical via-holes in the printed circuit board design, these liquid via-holes can implement routing of the microchannels linking up different microfluidic elements within the same device. We implement the parallel mixing operation using a via-hole integrated microfluidic device. This work exhibits the application opportunities in the more general integrated bio-microfluidic devices.
to generate liquid via-holes between two flow layers of flow channels to provide fluidic connection in microfluidic devices.  (Figure 1b). Afterwards, the PDMS substrate containing via-holes was peeled off from the mold and bonded to the remaining part of the device to finish the fabrication process.

Results and Discussion
A microfluidic device including the via-hole structures was developed for the testing of a parallel mixing operation. The design was optimized as a parallel channel network, enabling the combination of a matrix of different solutions. The device layout ( Figure   2a) contained an array of 4×4 chambers (diameter: 600μm), whose fluid flow was driven simultaneously by a shared peristaltic micro-pump [2]. Each chamber was connected to a "row" solution inlet and a "column" inlet, determined by its corresponding row (i)-col- mixing [6]. Notably, the characteristic length of diffusion was half of the channel height (5μm) that the mixing can be achieved along T-junction microchannels indicated in Figure 2b. d) The mixing performance was indicated by flow color dyes from the solution inlets.
As a demonstration, we applied color dyes to different solution inlets of the device in order to examine the parallel mixing operation Overall, the work demonstrated the microfluidic via-hole designs can realize integrated microfluidic functions, such as parallel mixing. This microfluidic via-hole technique can be further applied to general microfluidic designs for biomedical and applications [7].