Microfluidic perfusion system for maintaining viable heart tissue with real-time electrochemical monitoring of reactive oxygen species

Abstract

A microfluidic device has been developed to maintain viable heart tissue samples in a biomimetic microenvironment. This device allows rat or human heart tissue to be studied under pseudo in vivo conditions. Effluent levels of lactate dehydrogenase and hydrogen peroxide were used as markers of damaged tissue in combination with in situ electrochemical measurement of the release of reactive oxygen species (ROS). The parameters for perfusion were optimized to maintain biopsies of rat right ventricular or human right atrial tissue viable for up to 5 and 3.5 hours, respectively. Electrochemical assessment of the oxidation current of total ROS, employing cyclic voltammetry, gave results in real-time that were in good agreement to biochemical assessment using conventional, off-chip, commercial assays. This proof-of-principle, integrated microfluidic device, may be exploited in providing a platform technology for future cardiac research, offering an alternative approach for investigating heart pathophysiology and facilitating the development of new therapeutic strategies.

A Microfluidic System for Testing the Responses of Head and Neck Squamous Cell Carcinoma Tissue Biopsies to Treatment with Chemotherapy Drugs

“…With minor alterations to the device, we have already demonstrated that liver and cardiac tissues of similar size to the malignant biopsies can be maintained and studied; the latter being electrically stimulated. 6,13 The benefit of explant-based microfluidics other than allowing the replication of the in vivo microenvironment is that it also permits numerous analyses to be undertaken on a single biopsy over several days.…”

Heart-on-a-chip based on stem cell biology

“…The test on tissue biopsy in the microfluidic device was reported by Cheah et al (Cheah et al, 2010). They developed a microsystem to maintain viable and functioning heart tissue samples in a biomimetic microenvironment.…”

“…The next stage of microfluidic cardiac models is the development of 3D cell culture and biopsy analysis (Cheah et al, 2010, Khandemhosseini et al, 2007. The test on tissue biopsy in the microfluidic device was reported by Cheah et al (Cheah et al, 2010).…”

“…Heart models in microsystems presented in literature allow research on the single cells level (Kaneko et al, 2007, Ges et al, 2008, Murthy et al, 2006, Cheng et al, 2006, multicellular cultures (Nguyen et al, 2009, Nguyen et al, 2015, Pong et al, 2011, Annabi et al, 2013, Ren et al, 2013, Grosberg et al, 2011 and 3D tissue tests (Huang et al, 2007b, Horiguchi et al, 2009, Cheah et al, 2010, Chen et al, 2013 (Table 1). These microsystems are more representative experimental models of the in vivo environment, than conventional culture dishes.…”

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“…Microscale devices with gas control and oxygen monitoring functionalities have also been used for culturing cardiac tissue and physical stimulation of cardiomyocyte contractile function 43 . Those cardiac model systems have been used for assaying loss of membrane potential and cytochrome C release as an early manifestation of apoptosis typically observed following ischemia reperfusion.…”