A three-dimensional cell-laden microfluidic chip for in vitro drug metabolism detection

Abstract

Three-dimensional tissue platforms are rapidly becoming the method of choice for quantification of the heterogeneity of cell populations for many diagnostic and drug therapy applications. Microfluidic sensors and the integration of sensors with microfluidic systems are often described as miniature versions of their macro-scale counterparts. This technology presents unique advantages for handling costly and difficult-to-obtain samples and reagents as a typical system requires between 100 nL to 10 µL of working fluid. The fabrication of a fully functional cell-based biosensor utilizes both biological patterning and microfabrication techniques. A digital micro-mirror (photolithographic) system is initiated to construct the tissue platform while a cell printer is used to precisely embed the cells within the construct. Tissue construct developed with these technologies will provide an early diagnostic of a drug's potential use. A three-dimensional interconnected microfluidic environment has the potential to eliminate the limitations of the traditional mainstays of two-dimensional investigations. This paper illustrates an economical and an innovative approach of fabricating a three-dimensional cell-laden microfluidic chip for detecting drug metabolism.

A 3D printed microfluidic perfusion device for multicellular spheroid cultures

“…Although 3D printed microfluidic devices containing cell-laden hydrogels have been developed by a number of groups [15,16,21], this study marks a first demonstration of a 3D printed device capable of culturing multicellular spheroids. Microfluidic perfusion culture of multicellular spheroids often necessitates the presence of micro-structures (e.g.…”

“…However, the development of 3D printed microfluidic devices for organs-on-chip applications remains relatively under-explored. To date, a number of studies have already demonstrated the successful implementation of 3D printed microfluidic devices coupled with bioprinted [14][15][16][17][18][19][20] or photopatterned cell-laden hydrogels [21]. While this approach can recreate a 3D environment by supporting cells with synthetic or natural extracellular matrices and provide a means to probe cell-matrix interactions, it is limited in recapitulating multicellular interactions and organization, which is highly relevant to physiologically cell-dense tissues, such as tumors and hepatic tissues.…”

3D bioprinting for reconstituting the cancer microenvironment

“… 66 , 67 ). Such methodology can be applied to deposit cells with multi-nozzle deposition systems over channels built by a digital micro-mirror technique 68 . Integration of multi-head bioprinting with a maskless solid-freeform fabrication system was also developed, which speeded up the fabrication process and eliminated toxic chemicals.…”

Rapid Prototyping of Multilayer Microphysiological Systems

“…Moreover, initial prototyping may require multiple iterations and lithographic mold fabrication can be prohibitively expensive ($150-$500 per design from 3 rd party manufacturers). Other investigators have 3D printed microfluidic cell culture models 29,30 , but these single channel devices do not integrate membranes for recapitulating tissue-tissue interfaces. Therefore, in this study, we aimed to fabricate multi-layered, membrane integrated organs-on-chips without PDMS soft lithography.…”