Optimisation and analysis of microreactor designs for microfluidic gradient generation using a purpose built optical detection system for entire chip imaging

Abstract

This paper presents and fully characterises a novel simplification approach for the development of microsystem based concentration gradient generators with significantly reduced microfluidic networks. Three microreactors are presented; a pair of two-inlet six-outlet (2-6) networks and a two-inlet eleven-outlet (2-11) network design. The mathematical approach has been validated experimentally using a purpose built optical detection system. The experimental results are shown to be in very good agreement with the theoretical predictions from the model. The developed networks are proven to deliver precise linear concentration gradients (R(2) = 0.9973 and 0.9991 for the (2-6) designs) and the simplified networks are shown to provide enhanced performance over conventional designs, overcoming some of the practical issues associated with traditional networks. The optical measurements were precise enough to validate the linearity in each level of the conventional (2-6) networks (R(2) ranged from 0.9999 to 0.9973) compared to R(2) = 1 for the theoretical model. CFD results show that there is an effective upper limit on the operating flow rate. The new simplified (2-11) design was able to maintain a linear outlet profile up to 0.8 microl/s per inlet (R(2) = 0.9992). The proposed approach is widely applicable for the production of linear and arbitrary concentration profiles, with the potential for high throughput applications that span a wide range of chemical and biological studies.

A low resistance microfluidic system for the creation of stable concentration gradients in a defined 3D microenvironment

“…Our work presents a significant advance over previously reported techniques because our device does not require continuous fluid flow and allows stable concentration gradients to be formed in a 3-dimensional environment for a period of days (Li Jeon et al 2002; Mao et al 2003; Lin et al 2004; Zhu et al 2004; Biddiss and Li 2005; Chung et al 2005; Diao et al 2006; Irimia et al 2006; Lin and Butcher 2006; Saadi et al 2006; Amarie et al 2007; Cheng et al 2007; Chung et al 2007; Herzmark et al 2007; Li et al 2007, 2008; Park et al 2007; Yang et al 2007; Cheng et al 2008; Fok et al 2008; Kang et al 2008; Liu et al 2008; Motoo et al 2008; Shamloo et al 2008; Sun et al 2008; Atencia et al 2009; Cooksey et al 2009; Englert et al 2009; Glawdel et al 2009; Haessler et al 2009; Hattori et al 2009; Jeon et al 2009; Joong Yull et al 2009; Kalinin et al 2009; Kim et al 2009a; Park et al 2009; Siyan et al 2009; Yusuf et al 2009; Zhou et al 2009). Other devices produce gradients without continuous flow but are still limited to 2-dimensional geometries (with limited degrees of gradient stability) (Abhyankar et al 2006; Frevert et al 2006; Wu et al 2006; Du et al 2009; Kim et al 2009b), while others establish gradients in 3-dimensional environments but are dependent on fluid flow (Mosadegh et al 2007; Saadi et al 2007; Tingjiao et al 2009; He et al 2010; Zervantonakis et al 2010).…”

An integrated microfluidic array system for evaluating toxicity and teratogenicity of drugs on embryonic zebrafish developmental dynamics

“…[39][40][41][42][43][44] We presented a gradient network with seven branches of concentration at a spatial resolution based on previously employed principle of laminar flow in microchannels, 30 and 10 mol/ l sodium fluorescein was applied to quantify the resultant concentrations in the culture chambers. Although the fluorescent probes have a slightly higher diffusion coefficient than the test substances due in part to varying molecular weight between them ͑DOX, 580.0 g/mol; sodium fluorescein, 376.3 g/mol͒, the long serpentine channel would allow effective mixing for input solutions.…”

Concentration gradient generation methods based on microfluidic systems

“…These simplied networks were shown to provide enhanced agreement with designed molecular gradients over conventional designs and an effective upper limit of six times on the operating ow rate. 83 Campbell et al 29 proposed another structure shown in Fig. 3(b) and the difference was the wide combining chamber, where streams were split into three parts rather than two for conventional designs shown in Fig.…”