Monolithic Nanoplasmonic Microfluidic Device for Label-Free Cell Monitoring

The patent removes fluorescent labels and other molecular probes from the detection system. Instead of using labeled biomolecules for detection, the invention employs label-free detection methods that directly measure physical properties of cells and biomolecules, such as mass changes, refractive index variations, and mechanical properties, thereby eliminating the harmful biological interference caused by labeling while maintaining detection capability

The patent replaces optical detection methods based on fluorescent labeling with mechanical and physical detection methods. This includes using atomic force microscopy (AFM) for mechanical property measurement, quartz crystal microbalance (QCM) for mass detection, and other label-free optical techniques that detect intrinsic physical properties of the analyte without requiring external labels

The patent divides the detection system into multiple independent detection units, each capable of simultaneously analyzing individual cells or small groups of cells. This segmentation allows parallel processing of multiple samples (improving throughput) while maintaining precise control over each individual measurement (preserving uniformity), as each detection unit operates independently with controlled conditions

The patent employs microfluidic devices that create precise copies of standardized micro-environments for each sample. By using master molds and replication techniques, the system ensures that each well or detection chamber receives identical reagent volumes, concentrations, and physical conditions, thereby maintaining uniformity across high-throughput experiments

The patent creates master molds with precisely defined nanostructures using advanced lithography techniques before mass production. These master molds serve as templates that can be replicated multiple times, ensuring that each nanostructure is formed with high precision according to the original design. The preliminary creation of the master mold allows for precise control of nanostructure dimensions and spacing that would be difficult to achieve in direct fabrication

The patent uses nanoimprint lithography and other replication techniques to create multiple copies of nanostructures from a master template. This copying approach allows for mass production of nanostructures with uniform dimensions and spacing, as each structure is formed by direct replication rather than individual fabrication, thereby improving manufacturing precision while maintaining reasonable fabrication complexity

The patent removes fluorescent tags and optical probes from the cellular analysis system. Instead of labeling cells or proteins for imaging, the invention directly measures physical properties such as cell mass, volume, mechanical stiffness, and membrane properties using techniques like AFM, QCM, and other label-free methods, thereby eliminating steric hindrance and functional interference caused by fluorescent molecules

The patent replaces optical imaging methods with mechanical and physical measurement methods. This includes using atomic force microscopy to measure mechanical properties, quartz crystal microbalance to detect mass changes, and other label-free techniques that directly probe the physical state of cells and biomolecules without requiring fluorescent labels that could interfere with cellular function