Dual microfluidic perifusion networks for concurrent islet perifusion and optical imaging

Abstract

In this study, a new class of duplex microfluidic device is described that utilizes a dual perifusion network to simultaneously perform live-cell optical imaging of physiological activities and study insulin release kinetics on two islet populations. In addition, this device incorporates on-chip staggered herringbone mixers (SHMs) to increase mixing efficiency and facilitate the generation of user-defined chemical gradients. Using mouse islets, we simultaneously measure dynamic insulin release, changes in mitochondrial potentials, and calcium influx in responses to insulin secretagogues (glucose and tolbutamide), showing a high signal-to-noise ratio and spatiotemporal resolution of all measured parameters for both perifusion chambers. This system has many potential applications for studying β-cell physiology and pathophysiology, as well as for therapeutic drug screening. This dual perifusion device is not limited to islet studies and could easily be applied to other tissues and cells without major modifications.

Biology-inspired microphysiological system approaches to solve the prediction dilemma of substance testing

“…Other organs models in single-organ MPS include the small artery (Günter et al, 2010), the nervous system (Booth and Kim, 2012; Brown et al, 2014; Kermanet al, 2015; Nery et al, 2015; Park et al, 2009; Robertson et al, 2014; Taylor et al, 2005), the pancreas (Silva et al, 2013; Jun et al, 2013; Lee et al, 2012), the kidney (Snouber et al, 2012; Snouber et al, 2011; Jang et al, 2013; Ferrell et al, 2012; Kim and Takayama, 2015; Huang et al, 2013; Mu et al, 2013), the bone-marrow (Cui et al, 2007), the skin and hair (Atac et al, 2013) and the intestine (Esch et al, 2012 ; Kim and Ingber, 2013; Kim et al, 2012; Kim et al, 2013; Kimura et al, 2008; Lahar et al, 2011; Mahler et al, 2009; McAuliffe et al, 2008; Ootani et al, 2010; Sato et al, 2009; Sung et al, 2011; Yu et al, 2012) at different levels of biological complexity. Gao and colleagues (2013) designed an integrated microfluidic device directly coupled to a mass spectrometer, for instance, to characterize drug permeability of the intestinal barrier in a real-time manner.…”

Microfluidic Organ/Body-on-a-Chip Devices at the Convergence of Biology and Microengineering

“…Deficient production of digestive enzymes and hormones, as well pancreas blockage by tumors and gallstones, leads to subsequent malfunction of the entire digestive system and further compliances. Trying to solve these life-threatening conditions, researchers have made use of microfluidics to study and diagnose pancreatic cancer [ 125 , 126 , 127 , 148 ], culture pancreatic islets [ 112 , 113 , 114 , 138 ], monitor stimulus-secretion factors [ 139 , 140 , 143 ] and promote tissue-specific cell differentiation [ 124 ].…”

Transplantation of Encapsulated Pancreatic Islets as a Treatment for Patients with Type 1 Diabetes Mellitus

“…Recently, a microfluidic perifusion system has been introduced and developed in our research group. This system was designed to more precisely measure multiple key parameters that directly control β -cell insulin secretion and viability, such as mitochondrial electrical potentials, calcium influx, and insulin kinetics [ 85 – 87 ]. Most recently, this technology has been applied to evaluate microencapsulated islets.…”