Hybrid Three Dimensionally Printed Paper-Based Microfluidic Platform for Investigating a Cell’s Apoptosis and Intracellular Cross-Talk

Abstract

In this paper, we first proposed a novel hybrid three-dimensional (3D) printed and paper-based microfluidic platform and applied it for investigating the cell’s apoptosis and intracellular cross-talk. The fabrication of a 3D-printed microfluidic chip is much easier than polydimethylsiloxane (PDMS) chip and can be applied in many common labs without soft lithogrophy fabrication equipment. Moreover, 3D printing can be perfectly combined with paper-based chips that can provide 3D scaffold for cell culture and analysis. In addition, these paper chips are disposable after use, greatly reducing the experimental cost. We integrated “Christmas Tree” structure with the top layer of the 3D-printed microfluidic chip to generate a continuous concentration gradient, and the bottom layer contained paper-based chips as cell culture area. The two-layer structure allows the concentration gradient forming layer to be separated from the cell culture layer, which can simplify the planting of cells in the microfluidic chip and make sure the cells stay in the culture chambers and don’t clog the microfluidic channels. Applying this hybrid platform, we examined the effect of H2S on cancer cells. Continuous exposure to a low concentration of H2S inhibited cancer cell SMMC-7721 proliferation by inducing cell apoptosis. We also found that two gaseous molecules H2S and NO have cross-talk in cancer cells; they formed bioactive intermediate polysulfides in cancer cells. It is expected that this novel hybrid 3D-printed and paper-based microfluidic platform will have widespread application prospects in cell investigation.

Development of an on-chip sample injection system with a 6-port valve incorporated in a microchip

“…Recently, microchip fabrication by a 3D printer have attracted attention. 40 Although PDMS microchips are commonly fabricated by a photolithography technique using SU-8, simple fabrication methods using 3D printers have been recently reported. [41][42][43] Here, we fabricated a microchip made of PDMS using a template made with the DLP printing technique.…”

Research progress on the applications of paper chips

“…9.3.1 Fluorescence detection method. The uorescence detection method 13,18,46,63,77,82,85,86,94,95,98,112,113,129 is mainly used in combination with microuidic systems. It is mainly used to determine the uorescence samples and uorescent markers by using the uorescence of some substances emitted by light irradiation.…”

Recent Advances and Applications in Paper-Based Devices for Point-of-Care Testing

“…Through selection of electrode material and electrochemical technique, electrochemical detection was realized with fast response and high sensitivity [29]. Nowadays, to enrich these detection methods and achieve sensitive and accurate signal out-put, various micro-and nano-materials with different signal transduction mechanisms, such as metal nanoparticles [30,31], metal oxide [32,33], graphene or graphene oxide [34,35], quantum dots [36,37], hybrid materials [38,39] and metal-organic frameworks [40][41][42] have brought new breakthroughs in the design of new paper-based sensors. In addition, signal readers tend to be miniaturized.…”