Lab on a particle: 3D shape-coded microparticles for multiplexed cancer diagnostics

• Applicants: Professor Dr. Ghulam Destgeer; Professor Dr. Andreas Dietzel
• Subject Area: Primary Shaping and Reshaping Technology, Additive Manufacturing ; Biomaterials
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 494539689

Biochemical reactions performed inside miniaturized compartments have resulted in numerous applications in analyzing target biomarkers for diagnostic bioassays. Conventional methods to form uniform picolitre scale reaction volumes require microfluidic devices, specialized instruments, expensive cleanroom fabrication facilities, and expert users. To overcome such limitations, we propose an instrument-fee, user-friendly, and widely adoptable ‘lab on a particle’ approach to spontaneously form 1000s of isolated reaction volumes upon simply mixing reagents with our engineered amphiphilic microparticles. Our workflow is divided into two parts: (1) particle manufacturing and (2) particle-templated droplets for bioassay. Firstly, we will manufacture microparticles in bulk using a 3D-printed microfluidic device and an automated high-throughput stop-flow lithography process. The microfluidic device, fabricated by a high-resolution two-photon polymerization 3D printer, sculpts multiple precursor streams using a cascade of co-axial nozzles. The sculpted flow will be fully stopped and exposed to high-intensity UV light through a photomask to cure 3D shape-coded particles with <100µm outer diameter and <50µm cavity diameter. A detailed investigation of steady flow and stop flow dynamics will give the basis for determining the best conditions for particle shape fidelity in radial and axial directions. Consequently, the shape-coded particles with inner hydrophilic and outer hydrophobic layers will, for the first time, be so small that they can encapsulate aqueous droplets with a volume of <100 pL. The inner layers of the shaped coded particles will be functionalized to capture target biomolecules. The pL-volume compartments will speed up the enzymatic reactions performed within the aqueous droplets and rapidly accumulate the fluorogenic by-products to amplify the assay signals for high sensitivity detection compared to the state-of-the-art. A multiplexed amplification diagnostic assay will be performed within the shape-coded particle-templated droplets to detect three different biomarkers associated with ovarian cancer at clinically relevant concentrations.

• DFG Programme: Research Grants