Viable cell culture in PDMS-based microfluidic devices

Microfluidics has played a vital role in developing novel methods to investigate biological phenomena at the molecular and cellular level during the last two decades. Microscale engineering of cellular systems is nevertheless a nascent field marked inherently by frequent disruptive advancements in technology such as PDMS-based soft lithography. Viable culture and manipulation of cells in microfluidic devices requires knowledge across multiple disciplines including molecular and cellular biology, chemistry, physics, and engineering. There has been numerous excellent reviews in the past 15 years on applications of microfluidics for molecular and cellular biology including microfluidic cell culture (Berthier et al., 2012; El-Ali, Sorger, & Jensen, 2006; Halldorsson et al., 2015; Kim et al., 2007; Mehling & Tay, 2014; Sackmann et al., 2014; Whitesides, 2006; Young & Beebe, 2010), cell culture models (Gupta et al., 2016; Inamdar & Borenstein, 2011; Meyvantsson & Beebe, 2008), cell secretion (Schrell et al., 2016), chemotaxis (Kim & Wu, 2012; Wu et al., 2013), neuron culture (Millet & Gillette, 2012a, 2012b), drug screening (Dittrich & Manz, 2006; Eribol, Uguz, & Ulgen, 2016; Wu, Huang, & Lee, 2010), cell sorting (Autebert et al., 2012; Bhagat et al., 2010; Gossett et al., 2010; Wyatt Shields Iv, Reyes, & López, 2015), single cell studies (Lecault et al., 2012; Reece et al., 2016; Yin & Marshall, 2012), stem cell biology (Burdick & Vunjak-Novakovic, 2009; Wu et al., 2011; Zhang & Austin, 2012), cell differentiation (Zhang et al., 2017a), systems biology (Breslauer, Lee, & Lee, 2006), 3D cell culture (Huh et al., 2011; Li et al., 2012; van Duinen et al., 2015), spheroids and organoids (Lee et al., 2016; Montanez-Sauri, Beebe, & Sung, 2015; Morimoto & Takeuchi, 2013; Skardal et al., 2016; Young, 2013), organ-on-chip (Bhatia & Ingber, 2014; Esch, Bahinski, & Huh, 2015; Huh et al., 2011; van der Meer & van den Berg, 2012), and tissue engineering (Andersson & Van Den Berg, 2004; Choi et al., 2007; Hasan et al., 2014). In this chapter, we provide an overview of PDMS-based microdevices for microfluidic cell culture. We discuss the advantages and challenges of using PDMS-based soft lithography for microfluidic cell culture and highlight recent progress and future directions in this area.