Superconducting Cavity Readout for Multiplexed NEMS Mass Sensing

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Solution Overview

Problem

Current protein analysis methods, particularly in mass spectrometry, face challenges in directly analyzing intact proteoforms and multiproteoform complexes due to instrumentation limitations, leading to incomplete understanding of their structural characteristics and functions, and often result in the loss of rare analytes during preparatory protocols.

Innovation Solution

A highly-multiplexed cavity optomechanical readout system utilizing multiple nanoelectromechanical systems (NEMS) sensors coupled to a single microwave-frequency superconducting cavity resonator for efficient single-molecule analysis, enabling simultaneous readout of multiple sensors and improving mass resolution, responsivity, and reducing noise.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If multiple NEMS sensors are coupled to a single superconducting cavity resonator for multiplexed readout, then productivity and measurement precision are improved, but device complexity increases

Engineering Contradiction:
Improvethroughput analysis capacityVSAvoidsystem complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

Multiple NEMS sensors are coupled to a single superconducting cavity resonator, merging multiple sensing functions into one integrated system. This allows simultaneous readout of multiple sensors through frequency multiplexing, achieving high-throughput analysis of up to 60 million protein molecules while maintaining a compact architecture that avoids the complexity of multiple independent readout systems

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The superconducting cavity resonator serves as a universal readout mechanism for multiple NEMS sensors, each operating at different resonant frequencies. This multi-functional approach enables the single cavity to simultaneously detect signals from numerous sensors, dramatically improving productivity without requiring separate readout electronics for each sensor

Inventive Principle:
Principle #6Universality (Multi-functionality)

2Measurement precision

If conventional mass spectrometry methods are used for protein analysis, then ease of operation is maintained, but measurement precision and reliability are insufficient for intact proteoforms

Engineering Contradiction:
Improvemass resolutionVSAvoidoperational simplicity
Core Design Contradiction:
Measurement precisionVSEase of operation

Solution Approach 1:

The patent replaces conventional electromagnetic mass spectrometry detection with a mechanically-based NEMS resonator system. Each NEMS sensor acts as a mechanical balance that detects mass changes through resonant frequency shifts when molecules adsorb onto the sensor surface. This mechanical detection approach achieves superior mass resolution in the 100 Da range while maintaining operational simplicity through automated frequency tracking

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

3Loss of information

If bottom-up proteomics methods are employed, then ease of operation is improved, but loss of information occurs regarding intact proteoforms

Engineering Contradiction:
Improvestructural information preservationVSAvoidmethodological simplicity
Core Design Contradiction:
Loss of informationVSEase of operation

Solution Approach 1:

Instead of fragmenting proteins into peptides for analysis (bottom-up approach), the patent inverts the methodology by directly analyzing intact proteoforms and multiproteoform complexes. The NEMS sensors detect the mass and binding characteristics of complete protein molecules, preserving all structural information including post-translational modifications and protein-protein interactions, thereby eliminating information loss while maintaining operational simplicity

Inventive Principle:
Principle #13The other way round (Inversion)

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 allows for deep proteomic profiling of individual cells with high-throughput analysis of up to 60 million protein molecules, preserving rare species and enhancing mass resolution to the 100 Da range, overcoming the limitations of conventional methods.

Implementation Method 1

Cavity optomechanics generally refers to the coupling between electromagnetic radiation with micro- and nano-mechanical resonators

Methodology Applied
Scientific EffectCavity optomechanics:

Implementation Method 2

the coupling between electromagnetic radiation with micro- and nano-mechanical resonators

Methodology Applied
Scientific EffectElectromagnetic radiation coupling: Electromagnetic Induction

Implementation Method 3

multiple NEMS sensors coupled to a single microwave-frequency superconducting cavity resonator

Methodology Applied
Scientific EffectMechanical resonance: Resonance

Implementation Method 4

These quantum regime explorations can be carried out at temperatures well below 100mK

Methodology Applied
Scientific EffectSuperconductivity: Superconductivity

Data Source

PatentEP3924296B1Highly-multiplexed NEMS-array readout system based on superconducting cavity optomechanics
Publication Date: 2024.11.20 CALIFORNIA INST OF TECH
  • EP3924296B1 patent drawingFigure 1A~1D
  • EP3924296B1 patent drawingFigure 2
  • EP3924296B1 patent drawingFigure 3

AI summary

A NEMS readout system includes a sensor array comprising a plurality of sensors. Each sensor of the plurality of sensors including a resonator with frequency characteristics different from the resonator of each other sensor of the plurality of sensors. A readout signal indicative of a plurality of output signals is collected from the sensor array. Each output signal of the plurality of output signals corresponding to one of the plurality of sensors. An analysis of the plurality of output signals is performed to identify a plurality of resonant frequencies and to detect a frequency shift associated with at least one of the plurality of resonant frequencies.