Integrated Waveguide Velocimetry for Single Protein Detection
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current molecular analysis techniques face limitations in detecting low copy numbers and single cell protein concentrations due to low sensitivity and the need for complex, bulky, and expensive optical apparatus, which is not suitable for miniaturization.
Innovation Solution
The use of integrated optics with spatially distributed optical excitation and ultrasensitive particle detection based on individual electrokinetic velocity allows for the identification and quantification of molecular species in a fully integrated setting, enabling detection at low copy numbers down to single cell lysates through a lab-on-chip platform.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional CE techniques are used for molecular analysis, then detection sensitivity is limited to ng/mL levels (10^12-10^14 particles/mL), but the requirement for complex, bulky, and expensive optical apparatus prevents miniaturization
Solution Approach 1:
The patent segments the optical detection system into integrated waveguide components that can be fabricated on a chip substrate. The waveguide is divided into distinct functional regions (excitation region, detection region, separation region) that perform specific functions, enabling miniaturization while maintaining detection sensitivity through spatial distribution of optical functions
Solution Approach 2:
The patent replaces bulky mechanical optical apparatus with integrated optical waveguides that guide light through the sample channel. This substitution of mechanical optical components with integrated photonic structures enables miniaturization while maintaining the optical detection capabilities needed for sensitive molecular analysis
2Measurement precision
If mass spectrometry or liquid chromatography are used for protein analysis, then sensitivity reaches ng/mL levels, but the device complexity and cost increase significantly
Solution Approach 1:
The patent merges separation, detection, and analysis functions into a single integrated chip device. The electrophoresis separation channel is directly integrated with the optical waveguide detection system, eliminating the need for separate instrumentation systems and simplifying fabrication while achieving sensitive detection
Solution Approach 2:
The integrated chip performs multiple functions (separation, detection, and analysis) within a single device platform. The same chip can analyze different molecular species (proteins, nucleic acids, metabolites) by adjusting operational parameters, reducing the need for multiple specialized instruments
3Measurement precision
If single molecule spectroscopy is used for single cell protein detection, then detection sensitivity reaches single cell levels, but the optical apparatus becomes complex and bulky
Solution Approach 1:
The patent transitions from traditional bulk optical detection to waveguide-based evanescent field detection. By confining light to a sub-wavelength dimension within the waveguide, the evanescent field interacts with single molecules in the channel, enabling single-cell sensitivity while maintaining a compact footprint
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
This approach enables rapid, accurate, and sensitive molecular analysis with high specificity, overcoming the limitations of conventional methods by allowing for the detection of single molecules and reducing the complexity and cost of the required devices.
Implementation Method 1
a voltage source configured to generate an electrical field for inducing electrophoretic or electroosmotic flow of the particle in the channel
Implementation Method 2
a voltage source configured to generate an electrical field for inducing electrophoretic or electroosmotic flow of the particle in the channel
Implementation Method 3
one or more optical components configured to cause an excitation spot pattern to be incident on the channel, such that the particle is optically excited as it flows past the excitation spot pattern
Implementation Method 4
one or more optical sensors configured to detect a plurality of signal spikes emitted by the particle in response to the particle being illuminated by the excitation spot pattern, wherein the plurality of signal spikes comprises a first fluorescence signal spike emitted by the particle
Data Source
AI summary
Spatially distributed optical excitation and integrated waveguides are used for ultrasensitive particle detection based on individual electrokinetic velocities of particles. In some embodiments, chip-integrated systems are used to identify individual particles (e.g., individual molecules) based on their velocity as they move through an optically interrogated channel. Molecular species may be identified and quantified in a fully integrated setting, allowing for particle analysis including molecular analysis that can operate at low copy numbers down to the level of single-cell lysates. In some embodiments, the single-particle velocimetry-based identification and/or separation techniques are applied to various diagnostic assays, including nucleic acids, metabolites, macromolecules, organelles, cell, synthetic markers, small molecules, organic polymers, hormones, peptides, antibodies, lipids, carbohydrates, inorganic and organic microparticles and nanoparticles, whole viruses, and any combination thereof.