Aqueous Biphasic System for PSA Extraction

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Solution Overview

Problem

Current methods for extracting and quantifying prostate-specific antigen (PSA) from urine are invasive, time-consuming, and require sophisticated equipment, leading to challenges in early diagnosis and high costs, especially in underdeveloped and developing countries where prostate cancer mortality is high.

Innovation Solution

Aqueous biphasic systems (ABS) composed of ionic liquids and salts are used to simultaneously extract, concentrate, and purify PSA and its isoforms, allowing for complete extraction in a single step without protein loss, enabling quantification by simpler and more accessible laboratory equipment.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If traditional extraction methods (dialysis, filtration, precipitation) are used to concentrate PSA from urine, then PSA concentration is improved, but the process becomes time-consuming and requires multiple steps

Engineering Contradiction:
ImprovePSA concentrationVSAvoidextraction time
Core Design Contradiction:
Quantity of substanceVSLoss of time

Solution Approach 1:

The patent combines extraction, concentration, and purification of PSA into a single step using aqueous biphasic systems. The ionic liquid and salt form two phases that simultaneously perform all three functions, eliminating the need for sequential operations and reducing total processing time while achieving 10-1000 fold concentration.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The invention changes the physical-chemical parameters of the system by introducing ionic liquids with specific properties (viscosity, polarity, electrostatic interactions) that enable rapid phase separation and selective PSA partitioning. This allows the system to achieve high concentration factors without the time-consuming steps required by traditional methods.

Inventive Principle:
Principle #35Parameter changes

2Measurement precision

If sophisticated techniques (mass spectrometry, DNA microarray) are used for PSA detection, then detection sensitivity is improved, but equipment complexity and cost increase

Engineering Contradiction:
ImprovePSA detection sensitivityVSAvoidequipment sophistication
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent performs preliminary concentration and purification of PSA to 10-1000 fold before detection. This pre-treatment step raises the PSA concentration to levels that can be detected by simpler, less sophisticated equipment, eliminating the need for highly sensitive but complex instruments like mass spectrometry or DNA microarrays.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The aqueous biphasic system acts as an intermediary that transforms the low-concentration, complex urine matrix into a concentrated, purified PSA sample. This intermediate state enables the use of simpler detection methods while maintaining diagnostic accuracy.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Reliability

If invasive methods (digital rectal examination, biopsy) are used for prostate cancer diagnosis, then diagnostic accuracy is improved, but patient discomfort and procedural complexity increase

Engineering Contradiction:
Improvediagnostic accuracyVSAvoidinvasiveness
Core Design Contradiction:
ReliabilityVSEase of operation

Solution Approach 1:

The patent extracts and concentrates PSA from urine, a non-invasive biological fluid, to levels suitable for accurate detection. By obtaining sufficient biomarker from an easily collected sample, the method achieves diagnostic reliability comparable to invasive methods while avoiding patient discomfort and procedural complexity.

Inventive Principle:
Principle #2Taking out (Extraction)

4Measurement precision

If ELISA immunoassay is used for PSA quantification, then antigen identification is improved, but operational complexity and cost increase due to specialized antibodies and multiple steps

Engineering Contradiction:
Improveantigen identification accuracyVSAvoidoperational simplicity
Core Design Contradiction:
Measurement precisionVSEase of operation

Solution Approach 1:

The patent merges extraction, concentration, and purification into a single aqueous biphasic system step. This concentrated PSA preparation can then be analyzed by simpler methods, reducing the overall operational complexity while maintaining identification accuracy.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The patent performs preliminary concentration and purification of PSA before the detection step. This pre-concentration to 10-1000 fold eliminates the need for complex antibody-based methods, as the purified, concentrated sample can be detected by simpler techniques with comparable accuracy.

Inventive Principle:
Principle #10Preliminary action

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 method achieves high concentration factors (10-1000-fold) of PSA, enhancing diagnostic specificity and predictive value, and facilitating differential diagnosis, while being more economical and less invasive than existing techniques.

Implementation Method 1

aqueous biphasic systems are used, composed of ionic liquids and salts which allow the selective extraction of PSA and its isoforms, in particular the benign prostate-specific antigen (bPSA)

Methodology Applied
Scientific EffectAqueous biphasic system: Liquid-Liquid Extraction

Implementation Method 2

allow the selective extraction of PSA and its isoforms, in particular the benign prostate-specific antigen (bPSA) which is a specific molecular form of PSA found in the transition zone of patients suffering from benign prostatichyperplasia, to the ionic liquid-enriched phase, and its simultaneous purification and concentration

Methodology Applied
Scientific EffectSelective extraction: Liquid-Liquid Extraction

Data Source

PatentEP3875473A1Process for extracting, concentrating and purifying an antigen from a biological sample, composition and uses thereof
Publication Date: 2021.09.08 UNIV AVEIRO
  • EP3875473A1 patent drawingFigure 1~2
  • EP3875473A1 patent drawingFigure 3
  • EP3875473A1 patent drawingFigure 4A~4E

AI summary

The present disclosure refers to the development of a new method of pre-treatment of biological samples, preferably from human urine, comprising the simultaneous extraction, concentration and purification of the prostate-specific antigen (PSA), a biomarker for prostate cancer. In this method, aqueous biphasic systems are used, composed of ionic liquids and salts which allow the selective extraction of PSA and its isoforms, in particular the benign prostate-specific antigen (bPSA) which is a specific molecular form of PSA found in the transition zone of patients suffering from benign prostatic hyperplasia, to the ionic liquid-enriched phase, and its simultaneous purification and concentration.