This study presents a novel semi-permeable capsule (SPC) that isolates single cells while allowing selective biomolecular exchange, retaining larger biomolecules like genomic DNA while permitting smaller molecules to pass through. Using SPC-based single-cell whole genome sequencing (sc-WGS), researchers achieved high sensitivity and specificity in detecting genomic variants and successfully reconstructed cellular genealogies from cells harboring the hypermutator polymerase ε allele (POLE P286R).