Abstract
Sorption (i.e., adsorption and absorption) of small-molecule compounds to polydimethylsiloxane (PDMS) is a widely acknowledged phenomenon. However, studies to date have largely been conducted under atypical conditions for microfluidic applications (lack of perfusion, lack of biological fluids, etc.), especially considering biological studies such as organs-on-chips where small-molecule sorption poses the largest concern. Here, we present an in-depth study of small-molecule sorption under relevant conditions for microphysiological systems, focusing on a standard geometry for biological barrier studies that find application in pharmacokinetics. We specifically assess the sorption of a broad compound panel including 15 neuropsychopharmaca at in vivo concentration levels. We consider devices constructed from PDMS as well as two material alternatives (off-stoichiometry thiol–ene–epoxy, or tape/polycarbonate laminates). Moreover, we study the much neglected impact of peristaltic pump tubing, an essential component of the recirculating systems required to achieve in vivo-like perfusion shear stresses. We find that the choice of the device material does not have a significant impact on the sorption behavior in our barrier-on-chip-type system. Our PDMS observations in particular suggest that excessive compound sorption observed in prior studies is not sufficiently described by compound hydrophobicity or other suggested predictors. Critically, we show that sorption by peristaltic tubing, including the commonly utilized PharMed BPT, dominates over device sorption even on an area-normalized basis, let alone at the typically much larger tubing surface areas. Our findings highlight the importance of validating compound dosages in organ-on-chip studies, as well as the need for considering tubing materials with equal or higher care than device materials.
Highlights
Over the past decades, microfluidic devices and systems have moved from academia to the translational realm.[1]
Studies around the issue of PDMS compound sorption that is, non-specific absorption and adsorption, of small molecules (200−500 Da) started appearing as early as 2001.7 Attention to the phenomenon increased as the microfluidics field continued to expand, perhaps most notably after a widely cited 2006 study considering Nile red and quinine.[8]
We plot the resulting compound recovery fraction, that is, how much of the molecules of interest remained in solution, in Figure 2a for various microfluidic materials
Summary
Microfluidic devices and systems have moved from academia to the translational realm.[1] At the same time, academic applications have introduced more and more biological elements into microfluidic systems, starting with blood for point-of-care testing to complex cell ensembles for recapitulating human organ functions in vitro.[2−4] Such applications impose ever more rigorous requirements on the materials used in device construction.[5,6] One major criterion is whether the material alters the behavior or function of the biological element(s) that is to be assessed, that is, its “biocompatibility”. Thermoplastics (preferred for commercial production) and polydimethylsiloxane (PDMS; preferred in academic labs) generally perform well on this metric, though a case-by-case assessment is needed. Another important consideration is whether the material interferes with the chemical compounds to be tested, regardless if talking about a point-of-care biosensor or about drug testing using organs-onchips. With steady-state experiments, mathematical and computational models have shown some promise toward accounting for these effects in pharmacokinetic and pharmacodynamic studies.[18,19] With more complex dynamic compound-dosing studies, this becomes
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