Capillary Viscometry with Optical Detection for Biopharmaceuticals
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Solution Overview
Problem
Current techniques fail to simultaneously measure the viscosity, diffusion coefficient, and size of solutions, particularly for biopharmaceuticals and nanoparticles, without requiring dilution, which is necessary for accurate characterization and understanding their behavior in the body.
Innovation Solution
A method and apparatus using capillary viscometry with a high-resolution area imaging detector that measures specific viscosity by analyzing the time difference of a sample solution's flow front or plug passing through detection windows, allowing for simultaneous measurement of viscosity, diffusion coefficient, and size without dilution.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional UV absorbance or size exclusion chromatography is used to characterize biopharmaceutical formulations, then measurement of diffusion coefficient and hydrodynamic radius is possible, but sample dilution is required which affects the properties of the sample as formulated
Solution Approach 1:
The patent replaces mechanical/chromatographic separation systems with an optical detection system. Instead of using size exclusion chromatography which requires dilution and separation, the invention uses UV absorbance detection combined with Taylor Dispersion Analysis to measure diffusion coefficients and hydrodynamic radii directly in the undiluted sample, thereby maintaining sample formulation integrity while achieving accurate measurements
Solution Approach 2:
The patent changes the measurement parameters by using multiple detector locations along the capillary to simultaneously measure absorbance at different positions. This allows derivation of diffusion coefficients and hydrodynamic radii from the dispersion pattern without requiring sample dilution, thus resolving the contradiction between measurement accuracy and sample integrity
2Measurement precision
If capillary viscometry is used to measure viscosity, then viscosity measurement is achieved, but simultaneous measurement of diffusion coefficient and hydrodynamic radius using TDA has not been possible
Solution Approach 1:
The patent makes the capillary viscometry system universal by integrating multiple measurement capabilities into a single apparatus. The system can simultaneously measure viscosity through capillary flow, diffusion coefficients through Taylor Dispersion Analysis, and hydrodynamic radii through the same UV detectort, eliminating the need for separate instrumentation and enabling comprehensive characterization of biopharmaceutical formulations
Solution Approach 2:
The patent merges capillary viscometry and Taylor Dispersion Analysis into a single integrated system. By positioning multiple detectors along the capillary and using the same flow path for both viscosity measurement (via flow rate) and diffusion measurement (via dispersion pattern), the invention combines previously separate techniques into one versatile platform that provides multiple parameters simultaneously
3Measurement precision
If classic capillary viscometers are used, then viscosity measurement is possible, but large volumes of liquids are required which is cumbersome and problematic when only small sample volumes are available
Solution Approach 1:
The patent replaces the traditional mechanical timing system of classic capillary viscometers with an optical detection system. Instead of manually timing the meniscus movement, the invention uses UV detectors positioned at marked locations along the capillary to automatically detect the passage of the liquid, providing precise timing without requiring large sample volumes or manual intervention
Solution Approach 2:
The patent transitions from a single-point timing measurement to a distributed multi-point optical detection system. By placing multiple detectors at different positions along the capillary length, the system can measure viscosity using the flow rate information derived from the time it takes for liquid to pass between detector locations, thereby reducing the required sample volume 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 and precise measurement of viscosity and size of highly viscous samples with minimal sample volume, suitable for biopharmaceutical formulations, avoiding dilution and providing detailed characterization of concentration-dependent viscosity and protein interactions.
Implementation Method 1
detecting light from the light source passing through the carrier solution or the sample solution at each detector window using an array detector... generating an array detector output signal indicative of the profile of light absorbance
Implementation Method 2
pumping the plug of the sample solution through the capillary at a first pump pressure... determining the time difference between the time of detection of the sample solution plug or flow front at each detection window... calculating the specific viscosity from the time difference
Data Source
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AI summary
A method and apparatus for measuring the viscosity of a sample solution. A capillary (2) having first and second spaced apart detection windows (W1,W2) is filled with a carrier solution. A plug (4) or a continuous volume (4) of a sample solution is injected into the first end of the capillary (2) and pumped through the capillary (2) at a first pump pressure passing through the first and second detection windows (W1,W2). At least part of each detection window (W1,W2) is illuminated with a light source. Light from the light source passing through the carrier solution or the sample solution at each detector window (W1,W2) is detected using an array detector (6) comprising a two dimensional array of detector locations which generates an array detector output signal indicative of the profile of light absorbance of the sample solution plug (4) or flow front (4) passing through each detection window (W1,W2). From this the time difference between the time of detection of the sample solution plug (4) or flow front (4) at each detection window (W1,W2) is determined allowing the specific viscosity ?sp of the sample solution to be calculated taking into account a known time difference between the time of detection at each detection window (W1,W2) for a plug (4) or flow front (4) of a reference sample solution whose viscosity is approximately equal to the viscosity of the carrier solution when pumped at the first pump pressure.