BUN Sensor Using Immobilized Urease and Carbonic Anhydrase

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Solution Overview

Problem

Current methods for determining urea in biological samples, such as blood and urine, are limited in sensitivity and accuracy, especially in real-time or near-real-time applications, and do not effectively utilize carbonic anhydrase to enhance urea sensing in clinical settings.

Innovation Solution

A microfabricated sensor device with immobilized urease and carbonic anhydrase enzymes on a substrate, using a plasticized polyvinyl chloride layer and a water-permeable matrix, which enhances the conversion of urea to ammonium ions for precise potentiometric detection.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If a standard potentiometric sensor with urease is used, then the sensor can detect ammonium ions from urea conversion, but the sensitivity and accuracy of urea detection are limited

Engineering Contradiction:
Improveurea detection sensitivity and accuracyVSAvoidsensor performance stability
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

Carbonic anhydrase is introduced as an intermediary enzyme that mediates the conversion of bicarbonate to carbon dioxide, facilitating the overall urea detection process. This intermediary step enhances the sensitivity and accuracy of urea detection by improving the efficiency of the enzymatic reaction cascade.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The sensor utilizes changes in pH and carbon dioxide concentration as intermediate parameters to detect urea. By measuring these parameter changes through the enzymatic reactions, the sensor achieves higher sensitivity and accuracy in urea detection compared to direct ammonium ion measurement alone.

Inventive Principle:
Principle #35Parameter changes

2Productivity

If the sensor operates in real-time or near-real-time mode, then rapid detection is achieved, but the response time and stability may be compromised

Engineering Contradiction:
Improvedetection speedVSAvoidsensor stability
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The sensor maintains continuous enzymatic action through the coupled reactions of urease and carbonic anhydrase, ensuring uninterrupted conversion of urea to detectable signals. This continuous operation enables real-time detection while maintaining stability through the sustained catalytic activity of the enzyme system.

Inventive Principle:
Principle #20Continuity of useful action

Solution Approach 2:

The sensor undergoes preliminary calibration and stabilization steps before actual measurement, ensuring that the enzymatic reactions are fully activated and stable. This preliminary action prepares the sensor for rapid real-time detection while establishing stable baseline conditions.

Inventive Principle:
Principle #10Preliminary action

3Measurement precision

If the sensor uses multiple enzymes and complex layers, then detection capability is enhanced, but the device complexity increases

Engineering Contradiction:
Improveurea sensing accuracyVSAvoidsensor structure complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

Multiple functional layers containing different enzymes (urease and carbonic anhydrase) are merged into a single integrated sensor structure. This combining of multiple functional components into one unified device enhances detection capability while managing complexity through integrated design.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The sensor structure is designed to perform multiple functions: urea hydrolysis by urease, bicarbonate conversion by carbonic anhydrase, pH measurement, and carbon dioxide detection. This multi-functionality is achieved within a single integrated device, enhancing detection accuracy without proportionally increasing complexity.

Inventive Principle:
Principle #6Universality (Multi-functionality)

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

The solution significantly improves the sensitivity and accuracy of urea detection, reducing response time and increasing the stability and shelf-life of the sensors, making it suitable for rapid in situ measurements in clinical and point-of-care settings.

Implementation Method 1

The enzyme urease converts urea from the sample to ammonium ions

Methodology Applied
Scientific EffectEnzyme catalysis: Enzyme

Implementation Method 2

the enzyme urease converts urea from the sample to ammonium ions

Methodology Applied
Scientific EffectHydrolysis: Hydrolysis

Implementation Method 3

The enzyme carbonic anhydrase (CA) has been used in a carbon dioxide (pCO2) sensor

Methodology Applied
Scientific EffectEnzyme catalysis: Enzyme

Implementation Method 4

the bicarbonate formed by the urease reaction is converted to carbon dioxide by CA

Methodology Applied
Scientific EffectChemical conversion: Chemical Bonding

Implementation Method 5

The electrical potential at the electrode is a logarithmic function of the ammonium concentration and thus the bulk urea concentration

Methodology Applied
Scientific EffectPotentiometric detection: Electric Field

Implementation Method 6

a plasticized polyvinylchloride layer containing the ammonium ionophore nonactin

Methodology Applied
Scientific EffectIonophore transport: Permeation

Data Source

PatentUS8236517B2Blood urea nitrogen (BUN) sensor
Publication Date: 2012.08.07 ABBOTT POINT OF CARE INC
  • US8236517B2 patent drawing
  • US8236517B2 patent drawing
  • US8236517B2 patent drawing

AI summary

A BUN (blood urea nitrogen) sensor containing immobilized carbonic anhydrase and immobilized urease for the in vitro detection of urea nitrogen in blood and biological samples with improved performance and precision characteristics.