Small-Volume Liquid Mixing With Bubble-Sensor Pump Calibration
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Solution Overview
Problem
Current processes for preparing low volume liquid formulations, particularly in regenerative medicine and cell therapy, face challenges with high accuracy and consistency due to significant manual intervention, equipment tolerances, and the need for aseptic handling, which can lead to increased cell death and inefficiencies in processing time.
Innovation Solution
A liquid handling system comprising a reusable subsystem with a peristaltic pump, valve assembly, bubble sensors, and a system controller that enables precise measurement and calibration of fluid volumes, allowing for automated mixing and dispensing within a closed environment, reducing manual handling and operator variability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If manual processing is used for liquid formulations, then operator flexibility and adaptability are maintained, but accuracy and consistency deteriorate due to human variability and equipment tolerances
Solution Approach 1:
The system performs self-calibration using bubble sensors to detect fluid levels and automatically adjust pump parameters, eliminating the need for manual calibration while maintaining high accuracy in small volume dispensing
Solution Approach 2:
Manual mechanical calibration of scales and equipment is replaced with an automated electronic system using bubble sensors, peristaltic pumps, and electronic controllers that provide precise measurement and dispensing without human intervention
2Productivity
If manual handling is used for cell products, then processing time is extended, but cell viability deteriorates due to prolonged exposure to cryoprotectants
Solution Approach 1:
The system pre-calibrates pump parameters and pre-establishes dispensing protocols before cell processing begins, allowing immediate accurate dispensing when cell material arrives, thus minimizing the time cells are exposed to cryoprotectants
Solution Approach 2:
The automated system enables continuous operation without breaks for manual calibration or adjustment, maintaining uninterrupted processing that reduces total time from cell receipt to final dispensing, keeping cells in cryoprotectant exposure to the minimum necessary duration
3Measurement precision
If automated systems are implemented for liquid handling, then accuracy and consistency are improved, but system complexity increases
Solution Approach 1:
The peristaltic pump system automatically calibrates itself by detecting bubble positions with optical sensors and adjusting pump parameters accordingly, eliminating the need for external calibration equipment or manual intervention while maintaining high dispensing accuracy
Solution Approach 2:
Bubble sensors serve as intermediaries that provide simple optical signals to the control system, enabling accurate fluid level detection and pump calibration without requiring complex measurement instrumentation or manual operations
4Adaptability or versatility
If small batch processing is used for autologous products, then patient-specific customization is achieved, but processing efficiency deteriorates due to frequent manual interventions
Solution Approach 1:
The automated liquid handling system is designed to handle multiple different formulations and dispensing protocols through programmable control, allowing it to efficiently process various autologous product types without requiring separate manual procedures for each
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 system achieves high accuracy and consistency in low volume liquid formulations, reduces cell death by minimizing exposure time to cryoprotectants, and streamlines processing times, enhancing the efficiency and quality of cell therapy preparations.
Implementation Method 1
a peristaltic pump
Implementation Method 2
two or more bubble sensors each arranged to detect bubbles in a fluid path
Data Source
AI summary
Embodiments provide a liquid handling system arranged for preparation of small volume liquid formulations and dispensing these into output vessels. The system can be utilised for a variety of low volume liquid formulation preparation applications, with cell therapies being one example application.


