Abstract
We present a new, robust three dimensional microfabrication method for highly parallel microfluidics, to improve the throughput of on-chip material synthesis by allowing parallel and simultaneous operation of many replicate devices on a single chip. Recently, parallelized microfluidic chips fabricated in Silicon and glass have been developed to increase the throughput of microfluidic materials synthesis to an industrially relevant scale. These parallelized microfluidic chips require large arrays (>10,000) of Through Silicon Vias (TSVs) to deliver fluid from delivery channels to the parallelized devices. Ideally, these TSVs should have a small footprint to allow a high density of features to be packed into a single chip, have channels on both sides of the wafer, and at the same time minimize debris generation and wafer warping to enable permanent bonding of the device to glass. Because of these requirements and challenges, previous approaches cannot be easily applied to produce three dimensional microfluidic chips with a large array of TSVs. To address these issues, in this paper we report a fabrication strategy for the robust fabrication of three-dimensional Silicon microfluidic chips consisting of a dense array of TSVs, designed specifically for highly parallelized microfluidics. In particular, we have developed a two-layer TSV design that allows small diameter vias (d < 20 µm) without sacrificing the mechanical stability of the chip and a patterned SiO2 etch-stop layer to replace the use of carrier wafers in Deep Reactive Ion Etching (DRIE). Our microfabrication strategy allows >50,000 (d = 15 µm) TSVs to be fabricated on a single 4” wafer, using only conventional semiconductor fabrication equipment, with 100% yield (M = 16 chips) compared to 30% using previous approaches. We demonstrated the utility of these fabrication strategies by developing a chip that incorporates 20,160 flow focusing droplet generators onto a single 4” Silicon wafer, representing a 100% increase in the total number of droplet generators than previously reported. To demonstrate the utility of this chip for generating pharmaceutical microparticle formulations, we generated 5–9 µm polycaprolactone particles with a CV < 5% at a rate as high as 60 g/hr (>1 trillion particles/hour).
Highlights
Www.nature.com/scientificreports methods, architectures have been developed that make it possible to operate many microfluidic droplet generators in parallel[22,23]
Conventional Through Silicon Vias (TSVs) approaches cannot be applied to these architectures 1. because of the small foot-print of these TSVs (d < 20 μm), necessary to allow many microfluidic devices to be packed onto a single wafer, 2. because of the requirement of these chips for microfabricated features on both sides of the wafer, and 3. because of the stringent requirement for minimal debris and wafer warping such that the device can be permanently bonded to glass
We have increased the total number of droplet generators that can be incorporated onto a single wafer by reducing the size of the vias, resulting in a footprint (80 μm × 1.6 mm) for each droplet generator that is 50% smaller than that reported in our previous work (Fig. 1b,c)[20]
Summary
Www.nature.com/scientificreports methods, architectures have been developed that make it possible to operate many microfluidic droplet generators in parallel[22,23]. The microfabrication of Silicon to create highly parallelized microfluidic devices has several fabrication challenges, which have not been adequately addressed in prior studies[20] and which must be addressed to produce high performing chips with high yield. To demonstrate the utility of these fabrication strategies, we have developed a Very Large Scale Droplet Integration (VLSDI 2.0) chip that incorporates 20,160 flow focusing droplet generators onto a single 4” Silicon wafer, representing a 100% increase in the total number of droplet generators on a single chip than has previously been reported[1,2,4,5,6,9,20] Using these generators that are connected in a ladder geometry with only one set of inlets and outlets, we generated 1 trillion monodispersed droplets / hour with a CV < 5% for diameters ranging from 21–28 μm. We believe our fabrication strategy can be widely used to enhance the reliability of microfabrication of three-dimensional Silicon and glass microfluidic chips for a variety of applications
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