Abstract
Precision-cut tissue slices are an important in vitro system to study organ function because they preserve most of the native cellular microenvironments of organs, including complex intercellular connections. However, during sample manipulation or slicing, some of the natural surface topology and structure of these tissues is lost or damaged. Here, we introduce a microfluidic platform to perform multiple assays on the surface of a tissue section, unhindered by surface topography. The device consists of a valve on one side and eight open microchannels located on the opposite side, with the tissue section sandwiched between these two structures. When the valve is actuated, eight independent microfluidic channels are formed over a tissue section. This strategy prevents cross-contamination when performing assays and enables parallelization. Using irregular tissues such as an aorta, we conducted multiple in vitro and ex vivo assays on tissue sections, including short-term culturing, a drug toxicity assay, a fluorescence immunohistochemistry staining assay, and an immune cell assay, in which we observed the interaction of neutrophils with lipopolysaccharide (LPS)-stimulated endothelium. Our microfluidic platform can be employed in other disciplines, such as tissue physiology and pathophysiology, morphogenesis, drug toxicity and efficiency, metabolism studies, and diagnostics, enabling the conduction of several assays with a single biopsy sample.
Highlights
Tissue slices are sections of tissues harvested in vivo, excised, sliced, explanted and cultured in vitro
Device design and fabrication To work with these irregular tissue sections and perform multiple assays with an entire tissue excision, we developed a multilayer polydimethylsiloxane (PDMS) microfluidic device (Fig. 3a)
Ex vivo conventional techniques rely on static environments that alter nutrient supply and create oxygen gradients, detrimental for tissue culturing and impeding parallel experimentation on a single tissue sample[2,11,12,13,14]
Summary
Tissue slices are sections of tissues harvested in vivo, excised, sliced, explanted and cultured in vitro. Tissue-cut slices resemble the in vivo histology of an organ because they retain organ cytoarchitecture (to a certain extent), contain the different types of cells that make up an organ, maintain organ. Classic techniques for organotypic slice culture include roller tube cultures, membrane cultures, and petri dishes[2]. Tissue-cut slices from the liver, kidney, lung, brain, glands, heart, prostate, and spleen have been used in a wide range of applications including drug metabolism and discovery, physiology, morphology, development, endocrinology, and toxicology[2,9,10]. Most tissue slices can be cultured for up to 24 h; using dynamic organ culture incubation systems with appropriate culture media, oxygen supply conditions, and media perfusion, this period can be extended for up to 7 days[3] or even weeks to months[2]. Slices of different organs are prepared using similar straightforward techniques[10]. A major limitation of these techniques is that they require a de Hoyos-Vega et al Microsystems & Nanoengineering (2020)6:40
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