Reciprocal Injection Device for Protein Aggregation Testing

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Solution Overview

Problem

Conventional methods for testing pharmaceutical products, such as protein aggregation, lack precision in simulating shear and extensional hydrodynamic flow fields, which are crucial for assessing drug stability and container performance.

Innovation Solution

The development of reciprocal injection devices with a motor-driven platform, clamp fixtures, and a human-machine interface that allows for precise control of syringe plunger movement and fluid flow, enabling recirculation and concentration cycling through a narrowing and expanding channel setup.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional techniques are used to induce protein aggregation by passing fluid through a constriction, then protein aggregation can be observed, but the results lack accuracy, precision and repeatability due to absence of electronic interface for system actuation

Engineering Contradiction:

Improveaccuracy of aggregation resultsVSAvoidcomplexity of actuation system

Core Design Contradiction:

Measurement precisionVSDevice complexity

Solution Approach 1:

The patent replaces manual mechanical actuation with an electronic motor-driven system. The motor controls the plunger movement through a transmission mechanism, providing precise electronic actuation that eliminates the imprecision of conventional manual techniques while enabling accurate and repeatable measurement of protein aggregation.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The system incorporates an interface that allows selection and control of injection parameters, implying a feedback control mechanism. This enables precise control over the fluid flow and shear conditions, ensuring reproducible results by maintaining consistent actuation parameters across multiple tests.

Inventive Principle:

Principle #23Feedback

2Loss of substance

If material-sparing methods are implemented for conditioning formulations, then less pharmaceutical product is consumed, but the ability to accurately simulate hydrodynamic flow fields may be compromised

Engineering Contradiction:

Improveconsumption of pharmaceutical productVSAvoidaccuracy of flow field simulation

Core Design Contradiction:

Loss of substanceVSReliability

Solution Approach 1:

The reciprocal injection device performs periodic back-and-forth injection cycles, conditioning the formulation by repeatedly passing it through the constriction. This periodic action allows the same small volume of pharmaceutical product to be tested multiple times across different cycles, significantly reducing material consumption while maintaining simulation accuracy through consistent reproducible flow conditions.

Inventive Principle:

Principle #19Periodic action

Solution Approach 2:

The system continuously conditions the formulation through repeated reciprocal injections without requiring additional material. Each cycle builds upon the previous one, continuously exposing the same formulation sample to controlled hydrodynamic stress, thereby maintaining reliable simulation while minimizing substance loss.

Inventive Principle:

Principle #20Continuity of useful action

3Loss of substance

If reciprocal injection with recirculation is used, then material consumption is reduced and conditioning is improved, but the device complexity increases due to additional components

Engineering Contradiction:

Improveconsumption of formulation materialVSAvoidcomplexity of reciprocal injection system

Core Design Contradiction:

Loss of substanceVSDevice complexity

Solution Approach 1:

The motor-driven plunger system serves multiple functions: it controls the injection rate, enables reciprocal back-and-forth motion, and provides precise positioning. This multi-functional actuation mechanism reduces the need for separate components for each function, thereby limiting the increase in device complexity despite the added capability for material-sparing recirculation testing.

Inventive Principle:

Principle #6Universality (Multi-functionality)

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 solution provides a material-sparing method for conditioning protein formulations, allowing for accurate testing of product quality attributes and assessing the impact of hydrodynamic stress on pharmaceutical stability and container performance.

Implementation Method 1

simulating shear and extensional flow in syringes

Methodology Applied

Scientific EffectHydrodynamic flow:

Implementation Method 2

simulating shear and extensional flow fields

Methodology Applied

Scientific EffectShear stress: Shear Stress

Implementation Method 3

concentration cycling of formulations, such as protein-based formulations, as a result of the fluid flow through a narrowing and expanding channel

Methodology Applied

Scientific EffectConcentration cycling:

Data Source

PatentUS20240142356A1Reciprocal injection device and methods of using same

Publication Date: 2024.05.02 MERCK SHARP & DOHME LLC

AI summary

In some embodiments, a reciprocal injection device includes a platform having a motor, a gearbox operatively coupled to the motor, an actuation slide driven by the motor, a pair of clamp fixtures for supporting two syringes, a pair of axially translatable syringe plunger fixtures, and an interface in communication with the platform and configured and arranged to actuate the motor.