From DNA Detection to Organs-on-Chip Monitoring: Fabrication Solutions for Integrated Biosensing

QC 20260507

Abstract

Bringing a biosensor from laboratory demonstration to practical use depends as much on fabrication as on the sensing principle itself. This thesis develops fabrication strategies that overcome specific technological barriers across biosensing domains: from single-molecule electrochemical detection to real-time optical monitoring in organ-on-chip platforms.

In the electrochemical domain, the thesis identifies the conditions under which metal-assisted chemical etching enters the self-limiting regime in ultrathin silicon-on-insulator membranes, where catalyst size decouples from pore size, yielding ~5 nm pores with 1 nm variability (Papers I, II). A complementary approach translates micrometer-scale lithographic features into sub-10 nm pores through controlled fracture of pre-stressed membranes, validated for both electrical and optical single-molecule DNA detection down to 30 bases (Paper III). A two-tier fabrication architecture for organic electrochemical transistors decouples electrode routing from polymer channel definition via direct femtosecond laser writing, achieving single-micrometer resolution outside the cleanroom; channel outlining confines the ion-transport volume and improves switching speed by three orders of magnitude (Paper V). Colloidal self-assembly of polystyrene beads in silk fibroin produces biocompatible photonic crystals in which the defect-layer bead diameter programs the passband wavelength, establishing a design principle for spectral control in biocompatible optical structures (Paper IV). This fabrication logic, using particle size to define a functional feature in a host material, extends from the silicon nanopore work and enables the design of biocompatible photonic crystals.

In the optical integration domain, laser-machined PMMA modules with commodity optoelectronics replace benchtop instruments for continuous pH and dissolved oxygen monitoring in microfluidic systems (Paper VI). The modular architecture integrates with the bioreactor design without modification and operates autonomously from single-bioreactor cell culture through five-day multi-organ drug testing, enabling detection of liver-mediated drug conversion that is unobservable in single-organ systems (Paper VII).

Across those domains, understanding the sensing principle, material properties, and available fabrication tools guides the development of processes that achieve application-relevant precision while reducing costs and infrastructure requirements.

Link to DiVA