Search

Liver is the foremost organ of human being for drug metabolism, and it played a significant role in toxicity evaluation of drugs. Establishing a liver model in vitro can accelerate the process of the drug screening and new drug research and development. We provide a 3D printing based hepatic sinusoid-on-a-chip microdevice that reconstitutes organ-level liver functions to create a drug screening model of toxicity evaluation on chip. The microfluidic device, which recapitulates the hepatic sinusoid microenvironment, consists of PET polyporous membranes which mimic the perisinusoidal space, and experience fluid flow to mimic the hepatic arterial capillaries. The PET membrane was used to separate the hepatocyte and endotheliocyte. The endotheliocyte was cultured on the downside of the membrane and the hepatocyte were 3D seeded on the membrane via the 3D printer. This device was used to reproduce the in vitro liver model for drug toxicity assays. The expression of several biomarkers of liver was compared with the monoculture and 2D cultured conditions, and the results reveal that this organ-on-a-chip microdevice mimics the drug hepatoxicity that has not been possible by 2D cell-based and animal models, providing a useful platform for screening the drugs and developing an effective therapy in hepatopathy.

Blood–brain barrier on a chip (BBBoC) has emerged as a promising tool for high-throughput screening of central nervous system drugs. During the drug screening, it is essential to ensure high repeatability and consistency of assays in different culture units or chips with the same structures. For the assembled chip, cells are introduced into the inoculating chamber by perfusion. However, this method leads to differences between BBBoC because of the uncontrollable flow and sedimentation of the cell suspension in initial stages of cell inoculating. In this work, an inoculating-first and assembling-later method was presented to overcome the shortcoming. First, a porous membrane fixed between the PDMS brackets was made to support the cells. Then human brain microvascular endothelial cells and human astrocytes were respectively inoculated in turn onto the two sides of the porous membrane. When cells grew and occupied the porous membrane, the cell support was sandwiched between two glass substrates with microelectrodes for TEER detection. The method ensured high consistency of cell inoculating number on the porous membrane. Subsequently, a blood-brain barrier model in vitro with high trans-endothelial electrical resistance (TEER) value and expression of ZO-1 was achieved.

In vitro human blood-brain barrier (BBB) model is amenable to cellular studies on pathological and drug transport mechanisms related to the central nervous system (CNS). Compared with animal model of human, micro BBB ( $\mu \text{BBB}$ ) based on microfluidic chips is closer to in vivo phenotype and is more reproducible. Porous semipermeable membranes are integral components of the chip model, which provide cellular interfaces and help establish barrier models. This study proposes a convenient and low-cost fabrication method for ultra-thin micro-porous poly(dimethylsiloxane) (PDMS) membrane, which is inspired by paraffin section technique in immunohistochemistry. Microporous PDMS was obtained from the cured emulsion of PDMS pre-polymer containing uniformly dispersed micro-droplets of water. Cured microporous PDMS was embedded in paraffin to enhance the hardness and then sliced into membrane with a paraffin slicing machine. The minimum thickness of the membrane is $10\ \mu \mathrm{m}$ and smallest pore of $1\ \mu \mathrm{m}$ . The pore size and porosity of the membrane can be adjusted by controlling the water content and mixing time. To prove proof-of-concept, the immortalized human cerebral microvascular endothelial cell line (hCMEM/D3) was seeded on the membrane in a BBB-on-chip. This method provides a potential solution to simply prepare customized PDMS membranes for researchers in biomedical laboratory without micromanufacturing equipment.