Towards Personal Health Monitoring: Detecting Biomolecules with Microfluidics and Nanoplasmonic Sensors Fabricated by Nanoimprint Lithography

摘要

The research work presented in this dissertation includes the design, fabrication, and characterization of nanostructures for biosensing applications. The detection of proteins and nucleic acids with nanoplasmonic sensors in multiple formats (conventional 96-well plate, micro/nanofluidics) are discussed. Several related topics are also addressed: superposition of elementary nanostructures to form complex structures with an advanced multi-nanoimprint lithography (MNIL) fabrication method; and the integration of nanoplasmonic sensors with a microfluidic chip to make the chip a point-of-care (POC) device.;The first part of this dissertation reviews and compares cutting-edge lithography methods, specifically nanoimprint lithography (NIL) and photolithography. Nanophotonics and biosensing are identified as niche fields ripe for application of advanced NIL technologies through the study of the fields' characteristics.;The second part of this dissertation introduces the multi-nanoimprint lithography (MNIL) method with an example: superposition of the nanochannels and nanoplasmonic pillars. This method can be used to prepare complex nanostructures for biosensing applications.;The third and fourth parts of this dissertation cover the applications of disk-coupled dots-on-pillar (D2PA) in protein and deoxyribonucleic acid (DNA) detection, respectively. D2PAs with different resonance wavelength were fabricated to enhance the chemiluminescence and fluorescence signals. In addition, the systematic protocol optimization and novel biomolecular quantification method of a fluorescent DNA hybridization assay are described in detail. Ultimately, a record-high limit of detection (LoD) was achieved for the fluorescent DNA hybridization assay.;The final part of this dissertation demonstrates the integration of D2PA into microfluidic chips to make standalone point-of-care (POC) devices. The introduction of microfluidic channels into this assay system can drastically reduce the required assay time and quantities of reagents. The sample delivery is driven by the capillary force and requires no external power, which makes the POC device easy to use.;Overall, the work presented in this thesis will facilitate field testing of infectious diseases, as well as personal health monitoring.