Microfluidic Piezoelectric Sensor for Protein Viscosity Screening
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing methods fail to provide a rapid and accurate means to determine the propensity of proteins to undergo self-association under varying conditions, affecting the formulation, injectability, and manufacturability of biotherapeutics, particularly at high concentrations.
Innovation Solution
A microfluidic piezoelectric sensor with a serpentine channel structure on a piezoelectric resonator substrate is used to measure viscosity by generating shear motion, allowing determination of high and low shear-rate viscosities through resonance shifts, providing insights into the rheological properties of protein solutions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If proteins are concentrated to high levels (50-500 mg/mL) for subcutaneous injection, then the dosing volume is reduced, but the viscosity increases and colloidal interactions become problematic
Solution Approach 1:
The patent measures rheological properties (viscosity, elasticity, shear-thinning behavior) across different protein concentrations and conditions to identify optimal formulation parameters. By characterizing how viscosity and colloidal interactions change with concentration, pH, and temperature, formulators can adjust parameters to achieve high protein concentrations while maintaining acceptable rheological properties for injectability
Solution Approach 2:
The patent replaces traditional mechanical rheometry methods with a microfluidic acoustic wave sensor system that uses acoustic waves to measure viscosity and rheological properties. This substitution enables rapid, automated measurements with minimal sample volume, allowing extensive formulation screening without the time-consuming manual operations of conventional rheometers
2Measurement precision
If traditional rheological measurement methods are used, then comprehensive protein interaction data can be obtained, but the process is time-consuming and requires large sample volumes
Solution Approach 1:
The patent replaces traditional mechanical rheometry with an acoustic wave-based measurement system. Acoustic waves propagate through the protein solution in the microfluidic channel, and changes in wave velocity and attenuation provide rheological information. This substitution eliminates the need for mechanical contact and large sample volumes, reducing measurement time from minutes to seconds while maintaining accuracy
Solution Approach 2:
The patent transitions from bulk rheological measurements to micro-scale measurements in a microfluidic channel. By confining the protein solution to a thin channel and using acoustic waves that interact with the fluid in this confined geometry, the system achieves rapid measurements with nanoliter-scale sample volumes while capturing essential rheological behavior
3Reliability
If extensive formulation screening is performed to assess protein stability and rheology, then optimal formulations can be identified, but the development cost and resource requirements increase
Solution Approach 1:
The patent replaces resource-intensive manual rheological screening with automated acoustic wave measurements. The system can rapidly assess multiple formulation conditions (different concentrations, pH values, buffers, excipients) in sequence, providing comprehensive stability and rheology data without requiring extensive manual intervention or large sample volumes for each condition, thereby reducing development costs
Solution Approach 2:
The patent implements an automated measurement system where the microfluidic device autonomously handles sample introduction, acoustic wave generation, signal detection, and data analysis. The system requires minimal operator intervention and can continuously screen formulations, allowing development teams to assess more conditions with fewer resources and making extensive formulation screening economically feasible
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 rapid characterization of high concentration protein formulations, reducing development costs and risks by determining injectability and manufacturability with minimal sample volumes, thus de-risking candidate selection processes.
Implementation Method 1
a piezoelectric resonator substrate, a first electrode on a first surface of the piezoelectric resonator substrate, a second electrode of a second surface of the piezoelectric resonator substrate... the active area of the piezoelectric resonator substrate is configured to generate shear motion
Implementation Method 2
A high shear-rate viscosity of the analyte is determined based on a shift in resonance of the microfluidic piezoelectric sensor while driving the microfluidic piezoelectric sensor with the analyte in the channel
Data Source
Figure 1A
Figure 1B~1C
Figure 2A~2B
AI summary
A method is provided to measure viscosity of an analyte using a microfluidic piezoelectric sensor including a channel on an active area of a piezoelectric resonator substrate. The microfluidic piezoelectric sensor is driven so that the active area of the piezoelectric resonator substrate generates shear motion in a direction of shear motion displacement that is parallel with respect to a first surface of the piezoelectric resonator substrate. A high shear-rate viscosity of the analyte is determined based on a shift in resonance of the microfluidic piezoelectric sensor while driving the microfluidic piezoelectric sensor with the analyte in the channel. A low shear-rate viscosity of the analyte is determined by detecting flow of the analyte through the channel based on tracking shifts in resonance of the microfluidic piezoelectric sensor. Related sensors are also discussed.