The intrinsic heterogeneity of tumors makes the study of the underlying mechanisms of tumor spread and molecular diagnosis a real challenge. Therefore, it is of great interest to identify and understand these mechanisms in order to determine the most appropriate treatment for each patient.

Here, we describe an innovative microdissection platform called MiniPunch®. Based on the use of 200µm diameter and depth controlled single-use needles, this system is able to collect samples automatically in formalin-fixed paraffin-embedded (FFPE) blocks. Sampling of specific areas is enabled by the use of artificial intelligence that allows automatic alignment between the annotated virtual slide and the original FFPE block. A high sampling rate (~40 sec/sample) facilitates its routine use.

Our work aims to demonstrate the relevance of this technology for the study of intrinsic tumor heterogeneity. To this end, after validating the applicability of the technology, we performed RNA-seq on MiniPunch® samples obtained from human tumors. We were able to show variations in transcriptome expression with respect to both location and stage of disease. We also demonstrated the potential of this technology for molecular diagnosis by comparing it with routine techniques. The results showed increased sensitivity with MiniPunch® samples and access to critical information on intra-tumor heterogeneity that can improve the accuracy of established diagnosis.

This platform, capable of investigating tumor heterogeneity, will contribute to a better understanding of the complex mechanisms involved in tumor evolution. In this way, by improving molecular diagnosis, this system will contribute to the global development of precision medicine and thereby improve patient care worldwide.