Harnessing microfluidics for microbiology: from bacteria-host interactions to emerging cancer therapies.

Abstract

Microfluidics has emerged as a powerful technology for precisely controlling mechanical and chemical environments across a wide range of biological systems, from single cells to complex co-cultures. In microbiology, the microscale dimensions of bacteria pose experimental challenges that microfluidic systems have effectively addressed, offering compatibility with live imaging and enabling quantitative investigations of bacterial behaviors and host-bacteria interactions. Historical microfluidic designs are now routinely used to quantify bacterial growth and lineage with unprecedented temporal-spatial resolution and precise control of external conditions. In parallel, organ-on-chip technologies are increasingly applied in microbiology to study host-bacteria interactions within physiologically relevant and well-controlled microenvironments. Recently, cancer tissues have been recognized as unexpected hosts for bacteria, with mounting impactful evidence showing that intratumoral microbes can influence cancer progression and response to therapy. Despite growing interest, the application of microfluidics to cancer-bacteria interactions remains limited. Addressing this gap requires the development of appropriate methodological tools that replicate the relevant tumor microenvironment features and allow the quantification of both cellular responses and bacterial colonization dynamics upon the bacterial-host interaction. In this review, we first outline the foundational applications of microfluidics in microbiology from single-cell to collective behavior studies. We then describe how organ-on-chip technology enables the fine-tuned formation of organ-specific conditions, which are critical for modeling the complex tumor microenvironment. We further examine recent findings on intratumoral bacteria across cancer types and discuss how microfluidics, especially tumor-on-chip approaches, can advance this emerging field, from mechanistic insights to therapeutic development.