Sample Line Volume Calibration Through Fluid Boundary Detection
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Solution Overview
Problem
Current methods for measuring fluid sample volumes in microliter-scale analysis are imprecise, leading to waste of sample fluid and potential loss of valuable information, especially in detecting rare events, due to inaccurate determination of fluid line volume and sample arrival times.
Innovation Solution
A method involving delivering a calibration volume of a first fluid to completely fill a sample line, followed by a displacement volume of a second fluid, and using a sensor to detect the boundary between the fluids to estimate the sample line volume, allowing for precise determination of the sample fluid volume.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If current methods are used to measure fluid sample volumes, then manufacturing and operation are simpler, but measurement precision deteriorates leading to inaccurate line volume determination
Solution Approach 1:
The patent performs calibration actions before actual sample analysis. A calibration fluid is first introduced into the sample line to establish the relationship between pump displacement volume and actual fluid volume in the line. This preliminary calibration step creates a calibration factor that is stored and used during subsequent analyses, eliminating the need for complex real-time measurements during actual sample processing.
Solution Approach 2:
The patent uses a calibration fluid as an intermediary substance to determine line volume. Instead of directly measuring the sample fluid volume, the system introduces a known volume of calibration fluid, measures its travel time or position, and uses this intermediate measurement to calculate the line volume. This intermediary approach simplifies the measurement process while improving precision.
2Reliability
If larger margins of error are used for sample arrival times, then reliability improves to account for line volume variations, but loss of substance increases due to discarding more sample fluid
Solution Approach 1:
The patent uses the measured line volume to provide feedback that adjusts the calculated sample arrival time. By knowing the actual line volume from calibration, the system can precisely calculate when the sample will arrive at the detection point without needing to add large safety margins. This feedback mechanism allows for tighter timing windows and reduces the amount of sample that must be discarded.
Solution Approach 2:
The patent changes the parameter of sample arrival time calculation from using fixed conservative margins to using dynamically calculated values based on measured line volume. The system adjusts the arrival time parameter based on actual calibration data, allowing for more precise timing and reduced sample waste while maintaining reliability.
3Manufacturing precision
If careful sample line manufacturing methods are used, then manufacturing precision improves for consistent line volumes, but loss of substance increases due to discarding sample ends
Solution Approach 1:
The patent replaces reliance on precise mechanical manufacturing of sample lines with a calibration-based measurement system. Instead of depending on manufacturing precision to ensure consistent line volumes, the system uses a calibration step that measures the actual line volume and uses this information for accurate sample analysis. This substitution allows for the use of less precisely manufactured lines while maintaining measurement accuracy.
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
Enables accurate measurement of fluid volumes, reducing waste and increasing the usable sample fraction for analysis, particularly in cases with limited sample amounts, and improving data collection efficiency in instruments like flow cytometers.
Implementation Method 1
communicating the total volume from the sample zone to a sensor configured to identify a boundary between the first fluid and the second fluid
Data Source
AI summary
Provided are systems and methods for line volume calibration, and measurement of fluid samples delivered to an interrogation point. In various embodiments, a known fluid volume comprising a sample line fluid and a secondary fluid is delivered to a fluid boundary sensor. The fluid boundary sensor assists in determining the position of the boundaries between the various fluids, and the positions of these boundaries are used to determine the sample line fluid volume.