A thermoresponsive hydrogel poly(N-isopropylacrylamide) micropatterning method using microfluidic techniques

Abstract

Poly(N-isopropylacrylamide) (PNIPAAm) is a thermoresponsive hydrogel that has been widely used in various biomedical applications, including tissue engineering. Making PNIPAAm into a microscale structure is an effective method of increasing its thermoresponsiveness and modulating surface properties compared to bulk PNIPAAm. The commonly used method of direct photolithography combined with a photomask is challenging in creating pure PNIPAAm patterns smaller than 10 µm. Also, each time when there is a need to change the sizes of resulting PNIPAAm patterns, a new photomask is required. Here, a microfluidically controlled micropatterning method utilizing hydrophilic spots on a hydrophobic substrate was developed to create pure PNIPAAm microstructures. This method enabled the fabrication of pure PNIPAAm microstructures with a wide range of sizes from 70 µm to sub-10 µm out of the same substrate preparation by simply varying the flow speed of the hydrogel precursor solution through a microfluidic channel. Hydrogel microstructures with diameters of 12 to 59% of the hydrophilic pattern diameters were successfully fabricated using this fabrication scheme. The smallest hydrogel pattern fabricated using this method was 2.3 µm in diameter using a 5 µm diameter hydrophilic pattern at a flow speed of 100 mm s−1. This simple and versatile fabrication scheme could be an ideal method for creating large arrays of hydrogel micropatterns with varying sizes.