Nanoprobe Sensor Label-Free Intracellular Protein Detection

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Solution Overview

Problem

Current fluorescent imaging technologies face challenges in reliably labeling proteins within living cells, especially for non-transfectable cells, as it can alter protein dynamics and affect cell response.

Innovation Solution

The development of systems and methods for making and using sensors, including nanoprobe sensors, with a member comprising a starting portion, an end portion, and a tapered portion, where the end portion is nanometer-sized and can be inserted into cells to study cellular characteristics using optical techniques.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If fluorescent labeling is used to detect proteins in living cells, then detection capability is improved, but protein dynamics are altered and cell response is affected

Engineering Contradiction:
Improvedetection capabilityVSAvoidprotein dynamics
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The patent extracts the fluorescent label from the detection system and replaces it with label-free optical detection methods. The nanoscale probe enables direct detection of proteins without requiring fluorescent tags, thereby eliminating the interference that labels cause to protein dynamics while maintaining detection capability

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent replaces the chemical/biological labeling approach (mechanical system) with optical field-based detection (electromagnetic system). By using optical techniques such as optical tweezers and field-enhanced spectroscopy, the system achieves protein detection without physical or chemical modification of the target proteins

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

2Measurement precision

If GFP expression is used for protein detection, then fluorescent signal is obtained, but implementation difficulty increases for non-transfectable cells

Engineering Contradiction:
Improvefluorescent signalVSAvoidimplementation difficulty
Core Design Contradiction:
Measurement precisionVSEase of manufacture

Solution Approach 1:

The patent introduces an optical probe as an intermediary between the detector and the target protein. This probe delivers optical fields into non-transfectable cells and detects protein signals without requiring genetic modification of the cells, thus enabling fluorescent-like detection in cell types that cannot be transfected

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent creates an optical copy of the fluorescent detection capability without requiring actual fluorescent proteins. By using optical fields and nanoscale probes, the system replicates the signal detection function of GFP-based methods while avoiding the need for transfection and protein expression

Inventive Principle:
Principle #26Copying

3Measurement precision

If protein labeling is performed, then detection sensitivity is improved, but protein function is disrupted

Engineering Contradiction:
Improvedetection sensitivityVSAvoidprotein function
Core Design Contradiction:
Measurement precisionVSStability of the object's composition

Solution Approach 1:

The patent removes the labeling component entirely from the detection system. By using label-free optical detection methods, the system achieves protein detection without attaching any molecules to the target proteins, thereby preserving their native structure and function while maintaining detection sensitivity through field-enhanced optical techniques

Inventive Principle:
Principle #2Taking out (Extraction)

Data Source

PatentUS12324663B2Systems and methods for making and using sensors, probes, and other devices
Publication Date: 2025.06.10 PRESIDENT & FELLOWS OF HARVARD COLLEGE
  • US12324663B2 patent drawing
  • US12324663B2 patent drawing
  • US12324663B2 patent drawing

AI summary

The present invention generally relates, in some aspects, to systems and methods for making and using sensors or other devices, such as optical components. One aspect is generally directed to a sensor or other device comprising a nanometer-sized portion. In some embodiments, the sensor can be used to determine various characteristics such as temperature, humidity, an electric field, a magnetic field, an analyte, or the like. For instance, in one embodiment, a portion of a sensor device may be inserted into a cell and used to study the cell, e.g., using optical techniques such as surface plasma resonance. In some embodiments, such sensors or other devices may comprise metal, glass, or other materials, which can be prepared using etching or other techniques.