Maskless fabrication of cell-laden microfluidic chips with localized surface functionalization for the co-culture of cancer cells

Abstract

The utilization of the microfabrication technique to fabricate advanced computing chips has exponentially increased in the last few decades. Needless to say, this fabrication technique offers some unique advantages to develop micro-systems. Though many conventional microfabrication techniques today uses very harsh chemicals, the authors believe that the manipulation of system components and fabrication methods may aid in the utilization of the microfabrication techniques used in fabricating computer chips to develop advanced biological microfluidic systems. Presented in this paper is a fabrication approach in which popular fabrication methods and techniques are coupled together to develop an integrated system that aids in the fabrication of cell-laden microfluidic systems. This system aims to reduce the uses of harsh chemicals and decreases the lengthy fabrication time. Additionally, this integrated system will enable the printing of cells as the microfluidic chip is being fabricated. To demonstrate the unique capabilities of the integrated system, an advanced microfluidic chip is being fabricated and investigated. The advanced chip will feature the investigation of cancer cells in a co-cultured microfluidic environment. The investigations presented demonstrate co-cultures in a microfluidic chip, advanced cell printing with localized surface enhancement, cell integration, and full additive fabrication of a microfluidic chip.

3D-printed microfluidic chips with patterned, cell-laden hydrogel constructs

“…Other chips have been designed to examine drug transport across membranes and the effect of transported drugs on cells cultured on the membrane [47]. Several studies have demonstrated the use of 3D bioprinting to pattern microfluidic channels followed by cells deposited directly into the channels [48][49][50][51], including cocultures of multiple cell types [52]. 3D printing has also been used to generate cell cultures with hepatic sinusoid-like structures within fluid channels [53].…”

The recent development and applications of fluidic channels by 3D printing

“…The viability of encapsulated cells is impacted by the processing time of the pre-gel bio-ink preparation and the construct deposition and the sensitivity of different cell types to external stresses. The use of multi-nozzle printheads (e.g., photopolymer, UV, microplasma, bioink, etc) [ 119 ] for co-printing cell-laden hydrogels could decrease the printing time and maximize the cell viability [ 120 , 121 ]. It can be dedicated to printing the tissue constructs and the microfluidic channels simultaneously.…”

Advanced Fabrication Techniques of Microengineered Physiological Systems

“…Extrusion-based printing. Nevertheless, its technique has been applied to fabricate a chip to study cancer cells in a co-cultured microfluidic environment [50]. Inkjet printing has also been applied to a liver-on-a-chip to study drug metabolism and diffusion while showing the ability to utilize multiple cell patterns on a single chip [49].…”