Dynamic monitoring cell-free DNA using integrated diagnosis and therapy semi-implantable bioelectronics

Abstract

Continuous measurement of macromolecular biomarkers in vivo could enable diverse implantable applications in personalized medicine. However, technical obstacles remain: current technologies are limited to only one-way tracking of increases or decreases in macromolecule levels and lack real-time feedback on disease progression. Here, we propose an integrated diagnosis-therapy sensing system for dynamic tracking of cell-free DNA and drug delivery, based on a semi-implantable indwelling needle modified with clustered regularly interspaced short palindromic repeats (CRISPR)-dCas9. The specific binding-dissociation sensing mechanism of CRISPR-dCas9 with target DNA on the surface under fluctuating blood flow is discussed in detail, with various reaction equilibrium constants. Owing to the matched mechanical properties and geometrical structure of the semi-implantable device, it shows the ability to withstand interference of 60 % fetal bovine serum, sensitivity of 300 fM, 3-day stability, and real-time feedback on target DNA level in animal models. For sepsis patients bearing Staphylococcus aureus, the biosensor exhibited clinical sensitivity and specificity of 92.3 % and 100 % respectively. It could enable dynamic monitoring of cell-free DNA in vivo and timely intervention for patients with acute syndromes such as sepsis in the intensive care unit (ICU).