We show that a microfluidic chip designed with self-assembled 3D herringbone nanopatterns can detect low levels of tumour-associated exosomes in plasma that would otherwise be undetectable by standard microfluidic systems for biosensing
2019
Key concepts
- cancer diagnosis
- receiver operating characteristic
- human epidermal growth factor receptor 2
- area under the curve
- MINDS
- transmission electron microscopy
- Extracellular Vesicle
- Scanning electron microscopy
- computational fluid dynamics
- ovarian cancer
- circulating tumor cells
- monoclonal antibody
- phosphate-buffered saline solution
- nanoparticle tracking analysis
- nanolithography
- limit of detection
- Western blot
- epidermal growth factor receptor
- CD24
- Institutional Review Board
- surface area
- microfluidic chip
- liquid biopsy
Scholarcy highlights
- The performance of current microfluidic methods for exosome detection is constrained by boundary conditions and by fundamental limits to microscale mass transfer and to interfacial exosome binding
- We used the MINDS to combine micro-patterning and 3D nanostructuring of a widely used functional microelement, herringbone mixer for flow manipulation and molecular recognition. We showed that this 3D nanostructured herringbone addresses the aforementioned limits in one device effectively promotes microscale mass transfer of bioparticles20, 21; 2) increases surface area and probe density to enhance binding efficiency and speed; and 3) permits drainage of the boundary layer of fluid through the pores of a nano-HB, which reduces near-surface hydrodynamic resistance and enriches particles near the surface to enhance surface binding of particles
- The optimized 3-MPS treatment prevents the formation of cracks during thermal drying and minimizes the mechanical damages caused by removing the patterning chip, while preserving the nanoporosity
- These results suggest that utilizing the rich collection of nanomaterials and the flexibility of microfluidic design, the MINDS strategy affords broad applicability for microscale integration of designable 3D nanostructures to develop new multiscale integrated biosensing systems
- As a proof-of-concept, we evaluated the device as a diagnostic exosome analysis system for liquid biopsy-based detection of cancer
- Relevant to future clinical applications, we have investigated alteration of CD24, EpCAM and FRα protein expression in ovarian cancer-associated exosomes to demonstrate the feasibility for non-invasive biomarker profiling of cancer
- To characterize the nano-HB chip for exosome sensing, UC-purified extracellular vesicles of known concentrations were prepared by serial dilutions of the stock solution in 1 mL phosphate-buffered saline solution or 100 μL 10-fold diluted plasma; 20 μL of the solution was pumped through the chip at a flow rate of 0.5 μL/min by a micro-syringe pump
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