Silkworm Larva Screening for Innate Immunity via Muscle Contraction

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Solution Overview

Problem

Current methods for screening substances that activate or suppress the innate immune mechanism are hindered by the need for expensive cell culture equipment, false positives due to lipopolysaccharide contamination, and difficulties in administering substances to invertebrates like silkworm larvae.

Innovation Solution

A method utilizing muscular contraction in silkworm larvae as an indicator to evaluate substances for innate immune activation or suppression, eliminating the need for expensive equipment and avoiding false positives by administering the substance directly to the larvae, where it can be assessed for muscle contraction effects.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If cell culture method is used to screen innate immunity activators, then measurement precision is improved, but device complexity and cost increase

Engineering Contradiction:
Improvedetection accuracy of cytokine releaseVSAvoidequipment requirements for cell culture
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent extracts the essential screening function from complex cell culture systems and implements it using a simplified invertebrate model (silkworm larvae). The method isolates the key response (muscular contraction) and uses it as a direct readout for innate immunity activation, eliminating the need for cytokine detection equipment while maintaining screening capability.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent employs silkworm larvae as disposable test subjects that can be easily obtained, handled, and discarded after use. These invertebrate models provide a cost-effective alternative to mammalian cell culture systems, enabling high-throughput screening without requiring expensive infrastructure.

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

2Measurement precision

If conventional cell culture screening is used, then detection capability is improved, but false positives increase due to LPS contamination

Engineering Contradiction:
Improvedetection of innate immunity activationVSAvoidfalse positive rate
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The patent converts the potential harm of LPS contamination into a beneficial screening criterion. By using silkworm larvae that naturally respond to LPS through muscular contraction, the method actually benefits from LPS presence as a positive control signal, while the ability to distinguish between true activators and LPS responders is achieved through the specific contraction response pattern.

Inventive Principle:
Principle #22Blessing in disguise (Convert harm into benefit)

Solution Approach 2:

The patent introduces muscular contraction as an intermediary response marker between the test substance and the innate immunity system. This physical response serves as a reliable mediator that directly reflects true innate immunity activation without being confounded by cytokine detection artifacts or LPS contamination issues.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Ease of operation

If invertebrate models like silkworm larvae are used, then ease of operation is improved, but difficulty in administering test substances occurs

Engineering Contradiction:
Improvesimplicity of screening procedureVSAvoidadministration system requirements
Core Design Contradiction:
Ease of operationVSDevice complexity

Solution Approach 1:

The patent enables the silkworm larvae to self-administer the test substance through oral intake via food or water. The invertebrates naturally consume the test material, eliminating the need for complex injection systems or specialized administration equipment, while still achieving reliable absorption and response for screening.

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

This approach allows for simple and efficient screening of substances with innate immune activation or suppression properties, excluding substances with pharmacokinetic issues and lipopolysaccharide contamination, and identifying effective innate immunity activators and suppressors.

Implementation Method 1

an innate immunity activation substance such as peptideglycan is bound to a receptor on an immunocompetent cell (or humoral), and as a result, a reactive oxygen species (ROS) is produced

Methodology Applied
Scientific EffectReactive oxygen species production: Oxidation

Implementation Method 2

This facilitates a cascade of proteases, and leads to a change from a precursor (inactivated type) to an activated form of a (Bombyx mori) paralytic peptide BmPP

Methodology Applied
Scientific EffectProtease cascade: Enzyme

Implementation Method 3

the activated BmPP directly (or indirectly) acts upon a muscle cell to induce a muscular contraction

Methodology Applied
Scientific EffectMuscular contraction: Mechanical Force

Data Source

PatentEP2133693B1Screening method for substance having action of activating/suppressing innate immunity.
Publication Date: 2013.06.12 IMAGINE GLOBAL CARE CORP
  • EP2133693B1 patent drawingFigure 1
  • EP2133693B1 patent drawingFigure 2
  • EP2133693B1 patent drawingFigure 3

AI summary

It is intended to provide an evaluation method and a screening method capable of eliminating a substance that disturbs in vivo kinetics in an individual and capable of simply and easily searching a substance having an action of activating/suppressing an innate immune mechanism without being affected by LPS derived from bacteria, which can be contaminated during the search, as well as a drug and a food for activating/suppressing the innate immune mechanism, and methods of producing the same. The present invention provides a method of evaluating or screening the substance having the action of activating/suppressing the innate immune mechanism using a muscular contraction of an organism having the innate immune mechanism as an indicator, and methods of producing the drug and the food for activating/suppressing the innate immune mechanism. Also, an innate immunity activator and the food having the action of activating the innate immune mechanism containing the substance having the action of contracting the muscle of the organism having the innate immune mechanism, and an innate immunity suppressor and the food having the action of suppressing the innate immunity containing the substance having the action of suppressing the contraction of the muscle of the organism having the innate immune mechanism are provided.