Automated Dilution Series Preparation for Biosensor Calibration
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Solution Overview
Problem
The existing methods for preparing dilution series for biosensor systems, such as those using surface plasmon resonance, are time-consuming, prone to errors, and require a large number of wells, which can lead to contamination and inaccuracies in calibration curves, especially when dealing with low-intensity responses from small organic biomolecules.
Innovation Solution
An automated method for preparing dilution series using only two receptacles, where the second sample is mixed to achieve consistent concentrations, allowing for the creation of a correction curve over a wide concentration interval, including very low concentrations, and reducing the risk of errors.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If dilution series are prepared manually in multiple wells, then concentration gradients can be established, but the process becomes time-consuming and prone to errors
Solution Approach 1:
The patent divides the dilution series preparation into sequential steps using only two wells: (1) adding varying volumes of sample to a first well containing buffer, (2) transferring aliquots to a second well for mixing, and (3) injecting from the second well. This segmentation eliminates the need for multiple wells while maintaining concentration accuracy through controlled volume additions and thorough mixing.
Solution Approach 2:
The patent performs preliminary mixing of the sample and buffer in the second well before injection. By ensuring complete mixing beforehand, the method eliminates the need for multiple wells to establish concentration gradients, thereby reducing preparation time while maintaining precision through the mixing step.
2Reliability
If multiple wells are used for dilution series, then concentration variations can be achieved, but the risk of contamination and error increases
Solution Approach 1:
The patent merges the functions of multiple wells into a single well system. The first well serves for initial mixing of sample and buffer to establish concentrations, while the second well serves for final mixing and injection. This consolidation reduces the number of surfaces that can be contaminated, thereby improving reliability while using fewer wells.
Solution Approach 2:
The patent extracts the essential function of concentration establishment from multiple wells and concentrates it into a single well. By performing all dilution operations in one well and then transferring to a second well for injection, the method eliminates unnecessary wells that could introduce contamination, thus improving measurement reliability.
3Measurement precision
If reference measurements are performed at regular intervals, then calibration accuracy can be maintained, but the process becomes more complex and time-consuming
Solution Approach 1:
The patent enables continuous injection of samples with varying concentrations from the second well without requiring repeated setup of dilution series. The pre-mixed samples in the second well can be injected sequentially, maintaining calibration accuracy while improving throughput by eliminating repeated manual dilution operations between measurements.
Data Source
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AI summary
The present invention relates to a first embodiment of a method for preparing a dilution series, comprising the steps a. providing a first sample having a first concentration of a substance and a second sample having a second concentration of said substance, b. injecting a quantity of the second sample to the measuring device and registering at least one response from a measurement, c. altering the concentration of the second sample by adding an amount of the first sample to the second sample, d. injecting a quantity of the second sample generated in step c to the measuring device and registering at least one response from a measurement, e. repeating steps d) and e) until a predetermined number of responses have been registered, said predetermined number of responses being at least three, preferably at least four, more preferably at least eight. The invention also comprises a second embodiment of the method for preparing a dilution series and to a biosensor system arranged to perform the steps of the first or second method.