Micro-macro hybrid soft-lithography master (MMHSM) fabrication for lab-on-a-chip applications

Abstract

We present a novel micro-macro hybrid soft-lithography master (MMHSM) fabrication technique where microdevices having both microscale and macroscale features can be replicated with a single soft-lithography step. A poly(methyl methacrylate) (PMMA) master having macroscale structures was first created by a bench-top milling machine. An imprinting master mold having microscale structures was then imprinted on the PMMA surface through a hot-embossing process to obtain a PMMA master mold. A poly(dimethylsiloxane) (PDMS) master was then replicated from this PMMA master through a standard soft-lithography process. This process allowed both microscale (height: 3-20 microm, width: 20-500 microm) and macroscale (height: 3.5 mm, width: 1.2-7 mm) structures to co-exist on the PDMS master mold, from which final PDMS devices could be easily stamped out in large quantities. Microfluidic structures requiring macroscale dimensions in height, such as reservoirs or fluidic tubing interconnects, could be directly built into PDMS microfluidic devices without the typically used manual punching process. This significantly reduced alignment errors and time required for such manual fabrication steps. In this paper, we successfully demonstrated the utility of this novel hybrid fabrication method by fabricating a PDMS microfluidic device with 40 built-in fluidic interfaces and a PDMS multi-compartment neuron co-culture platform, where millimeter-scale compartments are connected via arrays of 20 microm wide and 200 microm long microfluidic channels. The resulting structures were characterized for the integrity of the transferred pattern sizes and the surface roughness using scanning electron microscopy and optical profilometry.

Keywords: Cast molding; Fluidic interface; PDMS; Soft-lithography.

Fig. 1

Schematic illustrations of PDMS microdevices fabricated by the MMHSM fabrication process. (a) A PDMS microfluidic device with 40 integrated fluidic interfaces and two reservoirs. (b) A PDMS multi-compartment microfluidic neuron co-culture platform. (Inset 1: Illustration showing the isolation of axonal layer inside the axon/glia compartment from neuronal soma and dendrites by the microfluidic channels, Inset 2: Cross-sectional view showing truncated cone shaped soma compartment)

Fig. 2

Fabrication and assembly steps to create a PDMS microdevice having two integrated macroscale reservoirs and 40 fluidic interfaces

Fig. 3

SEM images of (a) PMMA master, (b) PDMS master, and (c) PDMS device showing microchannels connected to millimeter-scale fluidic interfaces (Insets: Enlarged view of 500 μm wide channels). Scale bars, 200 μm. (d) Bottom-side of the PDMS multi-compartment neuron co-culture device showing arrays of 3 μm deep and 20 μm wide microfluidic channels connecting the soma compartment and the axon compartment. Scale bar: 50 μm

Fig. 4

Average height and width of the microchannels in the PMMA master, PDMS master and final PDMS device fabricated through the MMHSM process

Fig. 5

(a) A photographic image of a 3.5 mm thick PDMS microfluidic device (50×50 mm²) with 40 Teflon tubings connected to the integrated fluidic interfaces. Four different color dyes were used for visualization. (b) Schematic illustration showing the pressure threshold experimental setup