Protective Agent Composition for Circulating Tumor Cell Stabilization

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Solution Overview

Problem

Circulating tumor cells (CTCs) are fragile and prone to degradation during storage and transportation, leading to variability in enumeration and characterization, which complicates their use in cancer diagnosis and prognosis.

Innovation Solution

A protective agent composition is used in blood collection devices to inhibit cellular metabolic activity, preventing apoptosis and necrosis, allowing CTCs to be stored at room temperature for up to 14 days without significant degradation, eliminating the need for cold storage and preserving sample integrity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If blood samples are stored at room temperature during transportation, then ease of operation and device complexity are improved, but circulating tumor cells degrade due to apoptosis and necrosis

Engineering Contradiction:

Improveease of sample storage and transportVSAvoidcirculating tumor cell integrity

Core Design Contradiction:

Ease of operationVSReliability

Solution Approach 1:

The patent introduces a protective agent composition as an intermediary substance that mediates between the CTCs and the storage environment. This composition includes preservatives (e.g., phenol, thimerosal), antioxidants (e.g., vitamin C, vitamin E), and metabolic inhibitors (e.g., 2-deoxyglucose, sodium fluoride) that collectively protect CTCs from degradation during room temperature storage without requiring cold chain infrastructure.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the chemical parameters of the storage environment by adding protective agents that alter the metabolic state of CTCs. Specifically, metabolic inhibitors reduce glycolytic activity, preservatives prevent bacterial contamination, and antioxidants reduce oxidative stress, thereby changing the physiological parameters that would otherwise lead to cell degradation at room temperature.

Inventive Principle:

Principle #35Parameter changes

2Reliability

If cold storage is used to preserve circulating tumor cells, then circulating tumor cell integrity is improved, but device complexity and energy consumption increase

Engineering Contradiction:

Improvecirculating tumor cell integrityVSAvoidenergy consumption for cold storage

Core Design Contradiction:

ReliabilityVSUse of energy by stationary object

Solution Approach 1:

The protective agent composition serves as a chemical intermediary that replaces the need for physical cold storage infrastructure. By incorporating preservatives and metabolic inhibitors, the system achieves CTC preservation through chemical stabilization rather than thermal control, eliminating energy-intensive refrigeration requirements.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent replaces the mechanical/thermal system of cold storage with a chemical system of protective agents. Instead of using refrigeration equipment to maintain low temperatures, the invention uses chemical compounds to inhibit metabolic activity and prevent degradation, substituting a chemical preservation mechanism for a physical thermal control system.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

3Reliability

If rapid processing is performed to maintain circulating tumor cell integrity, then circulating tumor cell integrity is improved, but loss of time and productivity are worsened

Engineering Contradiction:

Improvecirculating tumor cell integrityVSAvoidtime for blood processing

Core Design Contradiction:

ReliabilityVSLoss of time

Solution Approach 1:

The protective agent composition is prepared in advance and added to blood collection tubes before phlebotomy. This preliminary action ensures that CTCs are protected from the moment of collection, eliminating the need for rapid subsequent processing. The preservative system is already in place to prevent degradation during any delays in processing.

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The protective agents act as intermediaries that extend the window of opportunity for CTC processing by stabilizing cells during transport and storage delays. This chemical mediation allows laboratories to process samples at their own pace without rushing, as the protective composition maintains CTC integrity throughout the extended timeframe.

Inventive Principle:

Principle #24Intermediary (Mediator)

4Stability of the object's composition

If aldehyde fixation is used to stabilize circulating tumor cells, then circulating tumor cell stability is improved, but harmful effects on cell structure and downstream analysis occur

Engineering Contradiction:

Improvecirculating tumor cell stabilityVSAvoidaldehyde damage to cell structure

Core Design Contradiction:

Stability of the object's compositionVSObject-affected harmful factors

Solution Approach 1:

The patent employs mild, non-crosslinking preservatives with short half-lives that provide temporary protection during transport without causing permanent structural changes. These disposable protective agents degrade or become inert after serving their protective function, leaving no harmful residues that would interfere with downstream molecular or cellular analyses.

Inventive Principle:

Principle #27Cheap short-living objects (Disposable)

Solution Approach 2:

The protective agent composition serves as a gentle intermediary that stabilizes CTCs through reversible mechanisms rather than permanent crosslinking. Preservatives prevent bacterial growth, antioxidants reduce oxidative damage, and metabolic inhibitors temporarily reduce metabolic activity without causing the irreversible structural changes associated with aldehyde fixation, thereby maintaining cell morphology and molecular integrity for downstream analysis.

Inventive Principle:

Principle #24Intermediary (Mediator)

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 method effectively maintains the integrity of CTCs, enabling accurate and precise analytical analysis, with CTC recovery rates remaining stable for several days post-blood draw, facilitating improved clinical analysis and diagnostic methodologies.

Implementation Method 1

The protective agent compositions described herein inhibit cellular metabolic activity in CTCs in blood and prevent cellular apoptosis and/or necrosis that degrades the CTCs in blood

Methodology Applied

Scientific EffectMetabolic inhibition:

Implementation Method 2

inhibit cellular metabolic activity in CTCs in blood and prevent cellular apoptosis and/or necrosis that degrades the CTCs in blood

Methodology Applied

Scientific EffectApoptosis inhibition:

Implementation Method 3

inhibit cellular metabolic activity in CTCs in blood and prevent cellular apoptosis and/or necrosis that degrades the CTCs in blood

Methodology Applied

Scientific EffectNecrosis prevention:

Data Source

PatentUS12114654B2Compositions and methods for stabilizing circulating tumor cells

Publication Date: 2024.10.15 STRECK LLC

AI summary

Compositions and Methods for Stabilizing Circulating Tumor Cells Methods and compositions for stabilizing a biological sample for analysis, comprising the steps of obtaining in a sample collection device a biological sample from a subject, especially blood, the biological sample including at least one circulating tumor cell from the subject. The methods may include a step of contacting the biological sample with a protective agent composition that includes a preservative agent, an optional anticoagulant, and a quenching agent to form a mixture that includes the protective agent composition and the sample.