Microfluidic Organoids-on-a-Chip: Quantum Leap in Cancer Research

Abstract

Organ-like cell clusters, so-called organoids, which exhibit self-organized and similar organ functionality as the tissue of origin, have provided a whole new level of bioinspiration for ex vivo systems. Microfluidic organoid or organs-on-a-chip platforms are a new group of micro-engineered promising models that recapitulate 3D tissue structure and physiology and combines several advantages of current in vivo and in vitro models. Microfluidics technology is used in numerous applications since it allows us to control and manipulate fluid flows with a high degree of accuracy. This system is an emerging tool for understanding disease development and progression, especially for personalized therapeutic strategies for cancer treatment, which provide well-grounded, cost-effective, powerful, fast, and reproducible results. In this review, we highlight how the organoid-on-a-chip models have improved the potential of efficiency and reproducibility of organoid cultures. More widely, we discuss current challenges and development on organoid culture systems together with microfluidic approaches and their limitations. Finally, we describe the recent progress and potential utilization in the organs-on-a-chip practice.

Keywords: living biobanks; microfluidics; organoids; organs-on-a-chip; tumoroids.

Figure 1

3D culture system of organoids. (a) Organoid formation using only a scaffold-Matrigel: (b) Organoid formation using spinning bioreactor: (c) Organoid formation using the Air-Liquid Interface method.

Figure 2

Applications of microfluidic organoid on-a-chip.

Figure 3

Preparation of a T-junction chip by photolithography (a–c) followed by soft lithography (d–f). (a) A negative photoresist is placed over a silicon wafer. (b) The photomask with a hole shaped on the desired chip pattern is placed over the photoresist and then illuminated. (c) After the development bath, only the negative photoresist exposed areas remain, obtaining the negative mold of the chip. (d) A liquid polymer (such as PDMS) is poured over the mold and allowed to polymerize. (e) The rubber-like material obtained after polymerization is peeled-off; it contains micro empty spaces, which are the channels of the chip. (f) The polymeric material is then sealed in its open part by bonding it to a layer, while at the opposite side, connectors are placed to allow the delivery of the fluids through channels.