Many cancer therapies fail in clinical trials despite showing potent efficacy in preclinical studies. One of the key reasons is the adopted preclinical models cannot recapitulate the complex tumor microenvironment (TME) and reflect the heterogeneity and patient specificity in human cancer. Cancer-on-a-chip (CoC) microphysiological systems can closely mimic the complex anatomical features and microenvironment interactions in an actual tumor, enabling more accurate disease modeling and therapy testing. This review article concisely summarizes and highlights the state-of-the-art progresses in CoC development for modeling critical TME compartments including the tumor vasculature, stromal and immune niche, as well as its applications in therapying screening. Current dilemma in cancer therapy development demonstrates that future preclinical models should reflect patient specific pathophysiology and heterogeneity with high accuracy and enable high-throughput screening for anticancer drug discovery and development. Therefore, CoC should be evolved as well. We explore future directions and discuss the pathway to develop the next generation of CoC models for precision cancer medicine, such as patient-derived chip, organoids-on-a-chip, and multi-organs-on-a-chip with high fidelity. We also discuss how the integration of sensors and microenvironmental control modules can provide a more comprehensive investigation of disease mechanisms and therapies. Next, we outline the roadmap of future standardization and translation of CoC technology toward real-world applications in pharmaceutical development and clinical settings for precision cancer medicine and the practical challenges and ethical concerns. Finally, we overview how applying advanced artificial intelligence tools and computational models could exploit CoC-derived data and augment the analytical ability of CoC.
In surface acoustic wave (SAW)-driven acoustofluidic tweezers (AFTs), most setups are integrated on a piezoelectric substrate for a single purpose, limiting the reusability and versatility of devices fabricated using complex MEMS technologies. Meanwhile, prevalent devices exhibit anisotropy in SAW excitation and propagation, as well as optical birefringence and limited transmittance. This work presents a SAW-driven modular acoustofluidic tweezer consisting of up to four replaceable interdigital transducer (IDT) modules and a function module assembled on a common base. Since the IDT modules are separated, each can be fabricated using the piezoelectric substrate best suited to the requirements. For example, SAWs generated from different directions can simultaneously propagate along the X-axis of 128° Y-cut LiNbO3, enabling highly efficient excitations. The generated SAWs couple into the function module with excellent optical properties and convert into Lamb waves, which then leak into the microfluidic domain and act on the fluid/particles. All modules are connected via standardized interfaces, eliminating potential instabilities caused by wired connections. The reliability of the setup is demonstrated via particle/cell patterning, separation, and concentration experiments, during which the replaceability and reusability of different modules, and the other advantages of the setup, e.g., simple assembly, ease of operation, and application flexibility, are proven.