A novel approach for precisely controlled multiple cell patterning in microfluidic chips by inkjet printing and the detection of drug metabolism and diffusion

Abstract

In this work we report the use of inkjet printing as a precise and convenient means for microscale cell patterning in microfluidic chips followed by cell co-culture, stimulation and analysis. A self-made inkjet printing device was manufactured with adjustable parameters, which was capable of multiple cell printing within biocompatible materials. Sodium alginate was used as a printing matrix for cell encapsulation, and precisely distributed cell arrays on glass slides were obtained by accurate software controlled printing. By covering a PDMS layer with the corresponding microchannels onto the cell array substrate and subsequently injecting an ion cross-linking reagent, the cells containing alginate arrays gelated immediately and were immobilized on the bottom of the microchip, which could be utilized for cell culture and analysis. HepG2 cells and U251 cells were successfully co-patterned in the microchip and used for drug metabolism and diffusion experiment to imitate the in vivo situation, as a means to ascertain the capability of the system for precise microscale cell patterning in a microchip. The prodrug tegafur was metabolized by HepG2 cells into the active anticancer compound 5-fluorouracil and this produced an adverse gradient effect on U251 cells according to the distance from the HepG2 cells. The developed approach presented a feasible way to integrate inkjet cell printing and microfluidic chips for the first time, which is proved to be capable of spatially controlled printing of multiple kinds of cells into a microchip for cell culture, stimulation and analysis, which could be applied to tissue engineering, drug testing and related areas. We envision that the approach will help significantly increase the cell patterning efficacy in microfluidic chips as well as reduce the extent of laborious experimental work.

Additive Manufacturing Approaches for Hydroxyapatite‐Reinforced Composites

“…Alginates are among the most used hydrogels for the production of biomaterial inks and bioinks: in fact, mild cross‐linking conditions, low costs, shear thinning properties, hydrophilicity, and fast gelation, which typically occurs in minutes, make alginate the optimal candidate for bioprinting processes . Despite different AM technologies being used for alginate processing, including droplet‐based printing and LAP, alginate‐based hydrogels and, in particular, alginate–HA composites are mainly processed by extrusion‐based technologies …”

Robotic Cell Printing for Constructing Living Yeast Cell Microarrays in Microfluidic Chips

“…We performed these dispensing steps with a piezoelectric dispenser (also called drop-on-demand ink-jet printing) [41,42]. Piezo printing of proteins and cells has been used previously for various applications including enzyme printing for glucose biosensors [43], protein arrays [44], netrin-1 adhesive micropattern construction [45], bacterial Escherichia coli arrays [46,47], bacterial and yeast cells on cantilever array sensors [48], S. cerevisiae cells on an agar layer [38], and mammalian cells [49].…”

Printed Microfluidics

“…(d) Schematic of a custom inkjet printer used to deposit hepatoma cells HepG2 (red) and glioma cells U251 (blue) on a glass substrate. Reproduced with permission . Copyright 2016, the Royal Society of Chemistry.…”