Automated Nematode Selection for Odorant Detection

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Solution Overview

Problem

Current methods for detecting molecular compounds using nematodes like Caenorhabditis Elegans are hindered by rapid reproduction leading to heterogeneous populations, high autofluorescence issues, and complexity in measuring neuronal responses, making extended and automated detection difficult, especially at an industrial scale.

Innovation Solution

An automated apparatus with mechanical and optical selection units to isolate nematodes by stage and size, followed by a measurement unit that analyzes neuronal responses to odorant substances, utilizing microfluidic channels, photodiodes, and LEDs to enhance detection efficiency and reliability.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If nematodes are used for detecting molecular compounds, then high chemo-sensitivity and chemotaxis are achieved, but rapid reproduction leads to heterogeneous populations making measurement complex

Engineering Contradiction:
Improvedetection reliabilityVSAvoidnematode population homogeneity
Core Design Contradiction:
ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent applies preliminary action by synchronizing nematode populations to a specific developmental stage (L4 larval stage) before detection. This is achieved through controlled culturing conditions and selective harvesting at defined time points, ensuring all nematodes are at the same developmental stage when exposed to odorants, thereby eliminating heterogeneity-induced measurement variability

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent changes the developmental stage parameter of nematodes by controlling cultivation time and environmental conditions. By harvesting nematodes at a specific time point corresponding to the L4 stage and maintaining them under synchronized conditions, the system ensures population homogeneity while preserving high detection sensitivity

Inventive Principle:
Principle #35Parameter changes

2Productivity

If nematodes in adult stage are used, then high detection efficiency is achieved, but high autofluorescence makes neuronal response measurement complex

Engineering Contradiction:
Improvedetection efficiencyVSAvoidautofluorescence interference
Core Design Contradiction:
ProductivityVSObject-generated harmful factors

Solution Approach 1:

The patent changes the developmental stage parameter from adult to L4 larval stage. This parameter change reduces autofluorescence by approximately 10-fold compared to adult nematodes while maintaining sufficient neuronal activity for detection, thereby improving signal-to-noise ratio in fluorescence-based neuronal response measurements

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent substitutes the use of adult nematodes (which have high autofluorescence) with L4 larval stage nematodes (which have low autofluorescence). This substitution maintains the biological detection function while eliminating the harmful autofluorescence interference, enabling more accurate neuronal response measurement

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

3Stability of the object's composition

If synchronized nematode rearing is performed with high accuracy, then population homogeneity is achieved, but the process becomes extended and difficult to automate

Engineering Contradiction:
Improvenematode population homogeneityVSAvoidsynchronization process complexity
Core Design Contradiction:
Stability of the object's compositionVSDevice complexity

Solution Approach 1:

The patent applies self-service by utilizing the nematodes' natural synchronized development cycle. By providing optimal cultivation conditions and allowing the population to develop synchronously through their inherent biological rhythm, the system achieves population homogeneity without requiring complex external synchronization mechanisms or manual intervention

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

The patent performs preliminary action by establishing synchronized cultures in advance through controlled seeding and cultivation. Once synchronized, the population maintains homogeneity for several days, allowing for extended measurement periods without requiring continuous re-synchronization, thereby simplifying the overall process

Inventive Principle:
Principle #10Preliminary action

4Extent of automation

If extended and automated detection is implemented, then industrial scale application is achieved, but current methods remain difficult to automate due to population heterogeneity

Engineering Contradiction:
Improvedetection automationVSAvoidnematode population homogeneity
Core Design Contradiction:
Extent of automationVSStability of the object's composition

Solution Approach 1:

The patent performs preliminary synchronization of the nematode population before automated detection begins. This pre-synchronization ensures that all nematodes are at the same developmental stage (L4) when introduced to the automated detection system, enabling consistent and reliable automated measurements without requiring continuous manual monitoring or adjustment

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent enables automated detection by allowing synchronized nematode populations to maintain their homogeneity through their natural developmental cycle. The system leverages the self-sustaining nature of synchronized cultures, which remain homogeneous for several days under optimal conditions, thereby facilitating extended automated operation without intervention

Inventive Principle:
Principle #25Self-service

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

The apparatus ensures a synchronized and efficient nematode population for compound detection, increasing signal-to-noise ratio, reducing false positives, and enabling rapid, reliable, and scalable molecular compound detection, while being compact and portable.

Implementation Method 1

The unit of separation of the nematodes on the basis of their vital stage downstream of the unit of separation thereof by size and specific weight

Methodology Applied
Scientific EffectDensity gradient separation: Density Gradient

Implementation Method 2

Current techniques of identification of odorant substances are based on the measurement of the fluorescence pulse that is generated when the nematode is separated from the stimulus due to the odorant substance under examination (neuronal activity)

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Implementation Method 3

an illuminator configured to illuminate the at least three measurement microfluidic channels and that is associated to double photodiodes

Methodology Applied
Scientific EffectLight Emitting Diode: Light Emitting Diode

Implementation Method 4

chemotaxis (phenomenon according to which unicellular or multicellular organisms direct their movements in function of the presence of chemical substances in the surrounding environment)

Methodology Applied
Scientific EffectChemotaxis:

Implementation Method 5

a connection channel with an at least three way branch and the optical selection unit being connected to the measurement unit by a loading microchannel

Methodology Applied
Scientific EffectPressure gradient flow: Pressure Gradient

Data Source

PatentUS11513106B2Apparatus and method for automatically detecting odorant substances in solution by using nematodes Caenorabditis Elegans
Publication Date: 2022.11.29 DISRUPTIVE TECHNOLOGICAL ADVANCES IN LIFE SCIENCE S R L SOCIETÀ BENEFIT
  • US11513106B2 patent drawing
  • US11513106B2 patent drawing
  • US11513106B2 patent drawing

AI summary

Apparatus (1000) and method for automatically detecting odorant substances based on use of nematodes that includes a mechanical selection unit (100) configured to select nematodes in adult stage from an initial nematode population obtaining an intermediate nematode population, a nematode optical selection unit (200) configured to select from the intermediate population a final population of nematodes in adult stage and to select nematodes in young adult stage from nematodes in egg producing adult stage to be sent to a measurement unit (300) configured to detect the response of nematodes of the final population to a stimulus of an odorant substance, the mechanical selection unit (100) being connected to the optical selection unit (200) by a connection channel with an at least three way branch and the optical selection unit (200) being connected to the measurement unit (300) by a loading microchannel.