Microfluidic Devices Containing ZnO Nanorods with Tunable Surface Chemistry and Wetting-Independent Water Mobility.

Interest in polydimethylsiloxane (PDMS) microfluidic devices has grown dramatically in recent years, particularly in the context of improved performance lab-on-a-chip devices with decreasing channel size enabling more devices on ever smaller chips. As channels become smaller, the resistance to flow increases and the device structure must be able to withstand higher internal pressures. We report herein the fabrication of microstructured surfaces that promote water mobility independent of surface static wetting properties. The key tool in this approach is the growth of ZnO nanorods on the bottom face of the microfluidic device. We show that water flow in these devices is similar whether the textured nanorod-bearing surface is hydrophilic or superhydrophobic; that is, the device tolerates a wide range of surface wetting properties without changing the water flow within the device. This is not the case for smooth surfaces with different wetting properties, wherein hydrophilic surfaces result in slower flow rates. The ability to create monolayer-coated ZnO nanorods in a PDMS microfluidic device also allows for a variety of surface modifications within standard mass-produced devices. The inorganic ZnO nanorods can be coated with alkyl phosphonate monolayers. These monolayers can be used to convert hydrophilic surfaces into hydrophobic and even superhydrophobic surfaces that provide a platform for further surface modification. We also report photopatterned biomolecule immobilization within the channels on the monolayer-coated ZnO rods.

An Integrated Microfluidics Approach for Personalized Cancer Drug Sensitivity and Resistance Assay.

Cancer is the second leading cause of death globally. Matching proper treatment and dosage is crucial for a positive outcome. Any given drug may affect patients with similar tumors differently. Personalized medicine aims to address this issue. Unfortunately, most cancer samples cannot be expanded in culture, limiting conventional cell-based testing. Herein, presented is a microfluidic device that combines a drug microarray with cell microscopy. The device can perform 512 experiments to test chemosensitivity and resistance to a drug array. MCF7 and 293T cells are cultured inside the device and their chemosensitivity and resistance to docetaxel, applied at various concentrations, are determined. Cell mortality is determined as a function of drug concentration and exposure time. It is found that both cell types form cluster morphology within the device, not evident in conventional tissue culture under similar conditions. Cells inside the clusters are less sensitive to drugs than dispersed cells. These findings support a heterogenous response of cancer cells to drugs. Then demonstrated is the principle of drug microarrays by testing cell response to four different drugs at four different concentrations. This approach may enable the personalization of treatment to the particular tumor and patient and may eventually improve final patient outcome.

Control and automation of multilayered integrated microfluidic device fabrication.

Integrated microfluidics is a sophisticated three-dimensional (multi layer) solution for high complexity serial or parallel processes. Fabrication of integrated microfluidic devices requires soft lithography and the stacking of thin-patterned PDMS layers. Precise layer alignment and bonding is crucial. There are no previously reported standards for alignment of the layers, which is mostly performed using uncontrolled processes with very low alignment success. As a result, integrated microfluidics is mostly used in academia rather than in the many potential industrial applications. We have designed and manufactured a semiautomatic Microfluidic Device Assembly System (µDAS) for full device production. µDAS comprises an electrooptic mechanical system consisting of four main parts: optical system, smart media holder (for PDMS), a micropositioning xyzθ system and a macropositioning XY mechanism. The use of the µDAS yielded valuable information regarding PDMS as the material for device fabrication, revealed previously unidentified errors, and enabled optimization of a robust fabrication process. In addition, we have demonstrated the utilization of the µDAS technology for fabrication of a complex 3 layered device with over 12 000 micromechanical valves and an array of 64 × 64 DNA spots on a glass substrate with high yield and high accuracy. We increased fabrication yield from 25% to about 85% with an average layer alignment error of just ∼4 µm. It also increased our protein expression yields from 80% to over 90%, allowing us to investigate more proteins per experiment. The µDAS has great potential to become a valuable tool for both advancing integrated microfluidics in academia and producing and applying microfluidic devices in the industry.