Tellurophene Mass Tags for Cellular Small-Molecule Detection

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Solution Overview

Problem

Current methods for monitoring the biodistribution and target engagement of small molecule therapeutics in vivo are limited by the need for high specific activities and technical challenges, and existing fluorescence-based techniques struggle to provide cellular resolution and multiplexing capabilities, hindering the application of mass cytometry in drug discovery and pharmaceutical development.

Innovation Solution

The use of tellurophene analogues, which are biocompatible mass tags, allows for the detection and quantification of small molecules like teniposide and carfilzomib through mass spectrometry, enabling their visualization and quantification at cellular and subcellular levels without requiring a MC-compatible element.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If fluorescence-based tissue histological techniques are used to visualize and quantify target engagement, then detection capability is improved, but cellular resolution and multiplexing capabilities are limited

Engineering Contradiction:

Improvedetection capabilityVSAvoidmultiplexing capabilities

Core Design Contradiction:

Measurement precisionVSAdaptability or versatility

Solution Approach 1:

The patent replaces fluorescence-based optical detection with mass cytometry detection using tellurium isotopes. This substitution enables multiplexed detection of multiple small molecules simultaneously without the spectral overlap limitations of fluorescence, while maintaining high sensitivity through mass spectrometry's inherent ability to resolve multiple masses in parallel

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent changes the detection parameter from optical fluorescence emission to mass-to-charge ratio measurement. By using tellurium isotopes with distinct atomic masses, multiple small molecules can be detected simultaneously through their unique mass signatures, enabling multiplexing beyond the capabilities of fluorescence-based methods

Inventive Principle:

Principle #35Parameter changes

2Measurement precision

If microautoradiography is used to monitor cellular biodistribution, then cellular resolution is improved, but exposure times and technical complexity increase

Engineering Contradiction:

Improvecellular resolutionVSAvoidexposure times

Core Design Contradiction:

Measurement precisionVSLoss of time

Solution Approach 1:

The patent replaces radioisotope-based microautoradiography with mass cytometry using stable tellurium isotopes. This substitution eliminates the need for long exposure times and radioactive handling while maintaining cellular resolution through laser ablation and mass spectrometric detection of tellurium-containing small molecules

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent uses stable, non-radioactive tellurium isotopes instead of radioactive tracers. This approach eliminates safety concerns and technical challenges associated with radioisotopes while providing sufficient detection sensitivity through the unique mass signature of tellurium in the mass cytometry instrument

Inventive Principle:

Principle #27Cheap short-living objects (Disposable)

3Measurement precision

If mass cytometry is applied to small molecules, then detection sensitivity is improved, but MC-compatible elements are required

Engineering Contradiction:

Improvedetection sensitivityVSAvoidapplicability to small molecules

Core Design Contradiction:

Measurement precisionVSAdaptability or versatility

Solution Approach 1:

The patent introduces tellurium as an intermediary element incorporated into small molecule structures. Tellurium serves as a mass tag that enables mass cytometry detection of small molecules without requiring modification of the detection instrument, bridging the gap between small molecule chemistry and mass cytometry capabilities

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent creates composite small molecule structures containing tellurium atoms integrated into the molecular framework. These tellurophene-containing small molecules combine the pharmacological properties of the parent compound with the detectability of heavy isotopes, enabling simultaneous therapeutic and detection functions

Inventive Principle:

Principle #40Composite materials

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 the detection and quantification of small molecules with cellular resolution, facilitating the design of dosing regimes and understanding perturbed cellular biochemistry, and providing insight into drug distribution and toxicity.

Implementation Method 1

detecting the tellurophene analogue in the sample using mass spectrometry

Methodology Applied

Scientific EffectMass spectrometry:

Data Source

PatentUS20250298027A1Method of evaluating small molecule distribution using tellurophene analogues

Publication Date: 2025.09.25 THE GOVERNING COUNCIL OF THE UNIV OF TORONTO

AI summary

The present disclosure relates to tellurophene analogues of small molecules, and methods of detecting small molecules using their tellurophene analogues. The present disclosure further relates to compositions and kits comprising tellurophene analogues of the present disclosure. The present disclosure also relates to methods of determining a dosage amount of a small molecule.