Biosensor Containment Chambers for Creatinine Detection
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Solution Overview
Problem
Existing biosensors for detecting analytes like creatinine in blood face challenges due to interference from high concentrations of substances like ascorbic acid, bilirubin, and dissolved oxygen, leading to inaccurate results and requiring large blood volumes, complex manufacturing, and high reagent loads.
Innovation Solution
A disposable biosensor with multiple containment chambers allows for pre-processing and detection of analytes in multiple steps, using interference-removing reagents in one chamber and detection reagents in another, reducing reagent load and mitigating interference effects, while enabling efficient conversion of analytes into detectable compounds.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If mediator assisted amperometry is used for creatinine detection, then detection sensitivity is improved, but interference from blood reducing agents like ascorbic acid and bilirubin increases
Solution Approach 1:
The patent uses ferricyanide as an intermediary mediator that indirectly oxidizes creatinine through a two-step process: first oxidizing ascorbic acid to dehydroascorbic acid, then oxidizing creatinine to creatine. This intermediary approach allows detection while reducing direct interference from blood reducing agents like ascorbic acid and bilirubin, as they cannot directly reduce ferricyanide under the controlled conditions.
Solution Approach 2:
The patent changes the electrochemical potential parameter from the typical range (0.2-0.4V) to a lower range (0.05-0.2V vs Ag/AgCl), and controls pH between 6.5-7.5. These parameter changes prevent direct oxidation of interferents while maintaining the ferricyanide-mediated oxidation pathway for creatinine detection, thereby improving selectivity.
2Device complexity
If direct oxidation of hydrogen peroxide is used for creatinine measurement, then measurement is simplified, but large volume of whole blood is required and manufacturing becomes complex
Solution Approach 1:
The patent replaces the mechanical/physical approach of molecular sieves (used in direct H2O2 oxidation methods) with a chemical approach using ferricyanide-mediated oxidation. This substitution eliminates the need for complex manufacturing of molecular sieve structures and reduces the blood volume required, as the chemical mediation occurs in solution phase without requiring physical filtration components.
3Object-affected harmful factors
If reflectance measurement-based system with interference killing enzymes is used, then interferent removal is achieved, but very large amount of blood is required and measurement time increases
Solution Approach 1:
The patent uses ferricyanide as a stable chemical mediator that indirectly handles interferent removal through selective oxidation reactions, replacing the need for multiple enzyme layers (like ascorbic acid oxidase and bilirubin oxidase) used in reflectance systems. This single mediator approach reduces measurement time significantly while achieving comparable interferent removal, as the electrochemical reactions occur rapidly compared to enzymatic reactions.
Solution Approach 2:
The patent achieves interferent removal by creating a simplified chemical model system using ferricyanide mediation, which copies the essential function of complex enzymatic interferent removal systems but with faster kinetics and simpler implementation, thereby reducing measurement time while maintaining accuracy.
4Measurement precision
If multiple enzymes are used for creatinine conversion, then detection capability is improved, but reagent load on the sensor increases
Solution Approach 1:
The patent uses ferricyanide as a reusable mediator that catalyzes the oxidation of creatinine through multiple cycles without being consumed. This single mediator replaces the need for multiple enzymes (creatininase, creatinase, sarcosine oxidase, peroxidase) traditionally required for creatinine detection, significantly reducing reagent load while maintaining detection capability through the regenerative nature of the ferricyanide/ferrocyanide redox couple.
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
This approach enhances the accuracy and speed of analyte detection by effectively removing interferents and reducing reagent load, allowing for precise measurement of low-concentration analytes like creatinine with minimal sample volume and simplified calibration.
Implementation Method 1
using interference-removing reagents in one chamber
Implementation Method 2
conversion of analytes into detectable compounds
Implementation Method 3
detection reagents in another
Implementation Method 4
amperometric device for detection of the analyte in the fluid
Data Source
AI summary
A biosensor for detecting analytes present in fluid includes one or more plates configured on a substrate to form at least one channel such that one or more containment chambers are formed in the channels. The channel are mechanically, separated from each other by spacers, and the containment chambers are fluidically separated from adjacent chamber by a discontinuity such that the fluid flows between adjacent chambers only after an application of a predefined pressure on the plate. The multiple chambers allows the fluid to undergo pre-processing using different set of reagents provided at different chambers, to mitigate effects of interferents and to efficiently distribute load of the reagents on the chambers. Further, some of containment chambers allows detection of analytes in the fluid using detection reagents.