Microwell Nanosensor Arrays for Single-Cell Analyte Detection
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Solution Overview
Problem
Current immunoassays have limited detection sensitivity, typically above 100 pg/ml, and are unable to detect intracellular molecules at the single cell level in a highly-multiplexed format, with flow cytometry being limited by the choice of antibodies and incompatible with most antibodies.
Innovation Solution
A microwell array with nanosensors comprising nanoparticles on nanostructures that interact via surface plasmonic, electric, or magnetic resonance to alter electromagnetic radiation, allowing detection of molecules through optical or color changes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional immunoassays are used for detection, then the detection method is simple and widely applicable, but the detection sensitivity is limited to 100 pg/ml and above
Solution Approach 1:
The invention segments the detection system into multiple functional components: nanosensors with specific antibody coatings, microwell arrays for single-cell isolation, and optical detection systems. This segmentation enables high sensitivity detection at the single-cell level while maintaining systematic organization and manageability of the overall assay process.
Solution Approach 2:
The patent introduces nanosensors as intermediary elements that bridge the gap between conventional immunoassays and single-cell detection requirements. These nanosensors, functionalized with specific antibodies, serve as mediators that capture target molecules from single cells and transduce the binding events into detectable optical signals, thereby achieving high sensitivity without requiring complex assay procedures.
2Adaptability or versatility
If flow cytometry is used for single cell analysis, then single cell detection is enabled, but compatibility is limited to only 10% of available antibodies
Solution Approach 1:
The nanosensor platform is designed with universal applicability to accommodate diverse antibodies. The nanosensor structure serves as a universal base that can be functionalized with any antibody of interest, enabling compatibility with the broad spectrum of available antibodies while maintaining single-cell detection capability through standardized nanosensor-micrawell integration.
Solution Approach 2:
The invention changes the detection parameters from conventional flow cytometry metrics to optical resonance-based measurements. By utilizing nanosensor-particle interactions that produce detectable optical signals, the system achieves enhanced detection sensitivity while maintaining versatility across different antibody types through standardized nanosensor functionalization protocols.
3Measurement precision
If conventional immunoassays are used, then bulk measurement is performed, but detection at single cell level is not achievable
Solution Approach 1:
The system segments the sample analysis into individual single-cell units using micrawell arrays, where each well isolates and analyzes a single cell. This segmentation enables precise single-cell measurement while maintaining productivity through parallel processing of multiple wells simultaneously, thus achieving both high measurement precision and acceptable throughput.
Solution Approach 2:
The invention transitions from conventional bulk liquid-phase measurement to a spatially-resolved single-cell analysis dimension. By confining individual cells in micrawells and positioning nanosensors for targeted interaction, the system adds the dimension of spatial control and single-cell resolution, enabling precise intracellular molecule detection while maintaining assay efficiency through standardized protocols.
4Measurement precision
If nanosensors with nanoparticles are used for detection, then detection sensitivity is enhanced, but device complexity increases
Solution Approach 1:
The nanosensor system uses nanoparticles as intermediary elements that enhance the detection signal without requiring complex device architecture. The nanoparticles, when bound to target molecules on the nanosensor surface, produce detectable optical resonance changes that amplify the detection signal, thereby achieving high sensitivity while keeping the overall device structure relatively simple and manageable.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
Enables detection of biomolecules and analytes at the single cell level with enhanced sensitivity, overcoming the limitations of conventional immunoassays and flow cytometry.
Implementation Method 1
the nanoparticle interacts with incident light via surface plasmonic resonance, electric resonance, and/or magnetic resonance
Implementation Method 2
the nanoparticle interacts with incident light via surface plasmonic resonance, electric resonance, and/or magnetic resonance
Implementation Method 3
the nanoparticle interacts with incident light via surface plasmonic resonance, electric resonance, and/or magnetic resonance
Implementation Method 4
determining the altered electromagnetic radiation
Data Source
AI summary
The present invention generally relates, in some aspects, to articles and methods relating to nanosensors for determination of molecules and other features, e.g., via surface plasmonic resonance, electric resonance, magnetic resonance, color changes, or the like. These articles and methods may be used, for example, for sample detection. The articles described in some aspects of the invention include a microwell array and a nanosensor array. In some embodiments, the nanosensor arrays may utilize nanoparticles positioned on nanostructures that are able to interact with a sample suspected of containing an analyte, such as a single cell. The interaction between nanoparticles and a sample can be detected by a change in applied energy, such as altered electromagnetic radiation caused by surface plasmonic resonance of incident visible light, and/or other types of resonance. Electromagnetic radiation may be applied to a microwell array and nanosensor, and the applied electromagnetic radiation may be altered as a nanosensor interacts with a sample suspected of containing an analyte. In addition, in some embodiments, the nanosensor arrays may utilize nanostructures and the binding of analytes may be determined based on optical or color changes.