Topographical mismatch sustains open microchannels in living soft tissue for non-destructive protein biopsy

Sustaining open microchannels within living soft tissue has remained a problem of mechanics: implants rigid enough to maintain patent channels inflict inflammation, while implants compliant enough to avoid it are sealed within minutes by viscoelastic recoil. Here, we resolve this conflict through topographical mismatch—a deliberate geometric non-conformity between an ultrathin multi-lobed implant and the surrounding tissue. Engineered to exceed the conformability limit of skin, these conduits sustain patency for over 42 hours of sustained physiological deformation and for at least 7 days in living skin without triggering the mechanotransductive signalling that initiates fibrotic encapsulation, and transmit macromolecules of up to 70 kilodaltons through intact skin—surpassing the molecular weight ceiling of transdermal iontophoresis. In vivo, this access reveals that interstitial fluid concentration of a model protein peaks 4.7-fold higher than serum at 2 hours, inverts at 8 hours and rebounds by 24 hours, uncovering tissue-level pharmacokinetics inaccessible to blood sampling. Topographical mismatch establishes a generalisable design principle for sustained, biocompatible interfaces between soft devices and living tissue. Skin-attached devices can easily inflame or collapse. Here, the authors show a multi-lobed microneedle device that holds micron-scale conduits open for seven days, allowing repeated protein sampling from interstitial fluid