Foreseeing treatment outcome in cancer patients is still a challenge that needs to be addressed. Tumors are complex structures, where the interaction between the tumor cells and the surrounding microenvironment regulates key processes in cancer progression, such as angiogenesis, evasion and modulation of the immune system response, and invasiveness. These interactions confer tumors a high heterogeneity not only inter-patient but also intra-patient. In vitro experimental models have been developed to preserve this heterogeneity present on tumor biopsies by the use of rotary wall and perfused bioreactors. However, the complexity and size of the bioreactors prevent from visual inspection of the sample and the realization of a high-throughput screening. The present work focuses on the combination of microfabrication techniques and microfluidics to downsize classic experimental models. The developed methodology requires only microliter size sample, and allows real time optical inspection.
A microscopy slide size optically transparent microfluidic bioreactor (µbioreactor) was designed and developed to preserve high cellularity on complex samples through constant perfusion. Colorectal carcinoma (CRC) biopsies were taken after previous patient consent was obtained. CRC biopsies were perfused by cell culture media in the µbioreactor during one week. After perfusion, CRC biopsies were histologically processed, stained and characterized by immunofluorescence.
High cellularity was observed in CRC biopsies after one week of perfusion. Stromal and parenchymal preservation was confirmed by both, histological staining and immunofluorescence.
The use of microfluidic bioreactors can be successfully used to preserve CRC biopsies, maintaining cell heterogeneity while allowing optical inspection. The use of small sample volumes (microliters) allows high throughput screening using regular biopsy samples, a key feature to achieve personalized treatments in cancer.
Clinical trial identification
Legal entity responsible for the study
University of Zaragoza
All authors have declared no conflicts of interest.