Yeast-Based Biosensor Peptide Detection

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Solution Overview

Problem

Current point-of-care (POC) diagnostics for peptides are limited, as existing technologies, such as sandwich immunoassays, cannot simultaneously bind a peptide with two antibodies, leading to long wait times and higher costs, making them unsuitable for immediate and cost-effective peptide detection in biological samples.

Innovation Solution

Development of yeast-based biosensors (YBBs) that utilize engineered recognition elements, like modified yeast receptors, to detect and quantify peptide analytes, featuring a surface-exposed receptor for binding and a reporter that signals peptide binding, enabling rapid and cost-effective detection.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If sandwich immunoassays are used for peptide detection, then antibody binding capability is improved, but device complexity and cost increase while measurement time extends to hours or days

Engineering Contradiction:
Improvepeptide detection capabilityVSAvoidmeasurement time
Core Design Contradiction:
ReliabilityVSLoss of time

Solution Approach 1:

The patent changes the fundamental detection parameters by replacing antibody-based recognition with engineered GPCR-based recognition elements in yeast cells. This parameter change enables peptide detection to occur within minutes rather than hours or days, while maintaining detection reliability through the engineered receptor-reporter system

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent substitutes the mechanical/chemical process of sandwich immunoassays with a biological sensing system using yeast-based biosensors. The engineered GPCRs in yeast cells detect peptides through natural ligand-receptor binding mechanisms, eliminating the need for complex antibody sandwich structures and extensive washing steps

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

2Reliability

If sandwich immunoassays are used for peptide detection, then detection capability is improved, but cost increases making them unsuitable for point-of-care use

Engineering Contradiction:
Improvepeptide detection capabilityVSAvoidcost
Core Design Contradiction:
ReliabilityVSEase of manufacture

Solution Approach 1:

The patent employs disposable yeast-based biosensors that are inexpensive to produce and use. The yeast cells serve as single-use detection units that can be discarded after one measurement, eliminating the need for expensive reusable equipment and complex reagent systems required by traditional immunoassays

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

Solution Approach 2:

The engineered yeast biosensors perform self-detection through their intrinsic GPCR signaling pathways. When the engineered GPCR binds the target peptide, it automatically triggers intracellular signaling that activates reporter gene expression, eliminating the need for external detection equipment or complex assay procedures

Inventive Principle:
Principle #25Self-service

3Measurement precision

If modified yeast receptors are engineered for peptide recognition, then sensitivity and specificity are improved, but device complexity increases

Engineering Contradiction:
Improvepeptide detection precisionVSAvoidbiosensor engineering complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent creates a universal yeast-based platform that can detect multiple different peptides by simply changing the engineered GPCR variant expressed in the yeast. The same yeast cellular machinery and reporter system handle all detection tasks, reducing overall system complexity despite the ability to detect multiple analytes with high precision

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

4Reliability

If frequent measurements are performed for disease monitoring, then treatment effectiveness is improved, but cost increases making frequent measurements impractical

Engineering Contradiction:
Improvetreatment monitoring accuracyVSAvoidmeasurement frequency
Core Design Contradiction:
ReliabilityVSProductivity

Solution Approach 1:

The patent enables continuous monitoring capability through rapid, repeatable measurements using yeast biosensors. The low cost and quick measurement time allow treatment monitoring to be performed continuously or frequently without accumulating prohibitive costs, maintaining continuous useful action for disease management

Inventive Principle:
Principle #20Continuity of useful 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

YBBs provide a low-cost, rapid, and sensitive method for detecting and quantifying peptides in biological samples, overcoming the limitations of existing POC diagnostics by enabling immediate results and frequent measurements.

Implementation Method 1

a recognition element (e.g., receptor (e.g., modified yeast receptor, etc.), etc.) on the exterior of the biosensor (e.g., for binding and or recognition of the analyte (e.g., peptide))

Methodology Applied
Scientific EffectReceptor binding:

Implementation Method 2

a recognition element binds a desired analyte (e.g., specifically), and sends a signal downstream (e.g., via G-protein or another signal transduction mechanism) to the reporter upon analyte binding

Methodology Applied
Scientific EffectSignal transduction:

Implementation Method 3

a reporter that signals binding or recognition of the analyte

Methodology Applied
Scientific EffectReporter signaling:

Data Source

PatentUS10690661B2Yeast-based biosensor
Publication Date: 2020.06.23 NORTHWESTERN UNIV
  • US10690661B2 patent drawing
  • US10690661B2 patent drawing
  • US10690661B2 patent drawing

AI summary

Provided herein are compositions and systems comprising yeast-based biosensors (YBBs) and methods of use thereof. In particular, YBBs are provided for the detection and/or quantification of an analyte (e.g., peptide analyte) in a sample (e.g., a biological sample, environmental sample, etc.). In some embodiments, provided herein are diagnostic compositions, devices, and methods comprising yeast-based biosensors (YBBs) engineered to detect analytes (e.g., peptides (e.g., biomarker peptides, etc.), etc.). In some embodiments, YBBs comprise (a) recognition element (e.g., receptor (e.g., modified yeast receptor, etc.), etc.) on the exterior of the biosensor (e.g., for binding and or recognition of the analyte (e.g., peptide)), and (b) a reporter that signals binding or recognition of the analyte. In some embodiments, a recognition element is a cell surface receptor.