Laser printing-enabled direct creation of cellular heterogeneity in lab-on-a-chip devices

Abstract

Lab-on-a-chip devices, capable of culturing living cells in continuously perfused, micrometer-sized channels, have been intensively investigated to model physiological microenvironments for cell-related testing and evaluation applications. Various chemical, physical, and/or biological culture cues are usually expected in a designed chip to mimic the in vivo environment with defined spatial heterogeneity of cells and biomaterials. To create such heterogeneity within a given chip, typical methods rely heavily on sophisticated fabrication and cell seeding processes, and chips fabricated with these methods are difficult to readily adapt for other applications. In this study, laser-induced forward transfer (LIFT)-based printing has been implemented to create heterogeneous cellular patterns in a lab-on-a-chip device to achieve the efficiency in creating heterogeneous cellular patterns as well as the flexibility in adapting different evaluation configurations in lab-on-a-chip devices. Two applications, parallel evaluation of cellular behavior and targeted drug delivery to cancer cells, have been implemented as proof-of-concept demonstrations of the proposed fabrication method. For the first application, the morphology of cells in different extracellular matrix (ECM) materials cultured under varying conditions has been investigated. It is found that less stiff ECM and dynamic culturing are preferred for spreading of fibroblasts. For the second application, different drug carriers have been utilized for targeted delivery of anticancer drugs to breast cancer cells. It is found that targeted drug delivery is important to realize effective chemotherapy and drug release rate from drug carriers affects the chemotherapy effect. Consequently, the proposed laser printing-based method enables direct creation of heterogeneous cellular patterns within lab-on-a-chip devices which improves the efficiency and versatility of cell-related sensing and evaluation using lab-on-a-chip devices.