Activable Fluorescence Probe for In Vivo Imaging
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current fluorescence imaging techniques face challenges with nonspecific signal noise from non-targeted regions, slow targeting kinetics, and short optimal observation times due to poor pharmacokinetics and light scattering in tissues, limiting the accuracy and contrast of in vivo imaging.
Innovation Solution
A molecular system with a targeted biological vector that activates an imaging function within the intracellular medium using a fluorophore linked to a fluorescence quencher by a cleavable arm, ensuring signal activation only after target cell internalization, thereby reducing background noise and enhancing signal intensity in the targeted region.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional luminescent labels are used for in vivo fluorescence imaging, then the imaging function can be performed, but nonspecific signal noise from non-targeted regions increases and targeting specificity decreases
Solution Approach 1:
The fluorophore is pre-linked to the biological ligand, but its fluorescence is initially quenched by a quencher molecule. The fluorescence is activated only after the probe binds to the target cell and is internalized, at which point the cleavable arm is cut and separates the fluorophore from the quencher. This preliminary quenching state ensures that no nonspecific signal is generated before target binding occurs.
Solution Approach 2:
The harmful quencher effect is extracted and separated from the fluorophore only after target binding occurs. The cleavable arm connects the fluorophore to the quencher, and its cleavage after internalization removes the quencher's suppressive effect, activating fluorescence specifically at the target site while eliminating background noise elsewhere.
2Measurement precision
If the probe binds to its receptor for targeting, then the target region can be visualized, but the probe is metabolized by the organism during this period, shortening the optimal observation time
Solution Approach 1:
The probe is designed to accumulate and bind to target cells before fluorescence activation occurs. The fluorophore remains quenched during the accumulation phase, allowing the probe sufficient time to reach and bind to target cells without premature signal generation. Only after binding and internalization does the fluorescence activate, ensuring both adequate targeting time and sustained observation window.
3Ease of operation
If fluorescence imaging is performed in vivo, then real-time noninvasive monitoring is achieved, but light scattering in tissues creates high background signal and reduces image contrast
Solution Approach 1:
The fluorescence signal is activated locally only at the target site after probe internalization. By using a cleavable arm that is cut specifically after cellular internalization, the invention ensures that fluorescence is generated only where the probe has successfully bound and entered the target cell, creating a localized signal that overcomes tissue scattering and improves image contrast.
4Adaptability or versatility
If biological ligands are used for targeting, then specific cells can be targeted, but the targeting kinetics are slow and 100% targeting cannot be achieved
Solution Approach 1:
The probe design allows the biological ligand to perform its natural targeting function without interference. The ligand binds to its receptor and facilitates probe internalization through normal cellular mechanisms. The fluorescence activation is then triggered automatically by the internalization process itself via cleavage of the arm linking the fluorophore to the quencher, eliminating the need for additional activation steps and maintaining fast, efficient targeting kinetics.
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 provides a targeted and sustained imaging response with reduced background noise, allowing for improved visualization and longer observation times of specific biological processes without the need for specific enzymatic activity, enhancing the specificity and clarity of in vivo imaging.
Implementation Method 1
The imaging function is provided by a fluorophore F linked to a fluorescence quencher by an arm cleavable in an intracellular medium
Data Source
AI summary
The invention concerns the field of molecular probe architecture for in vivo imaging. More particularly, the invention concerns molecular constructs providing an imaging function activable in intracellular environment. The inventive fluorescence probes enable in particular images of certain targeted tissues to be formed, while maintaining a low background noise level and, preferably, while obtaining at the targeted tissue, an imaging signal increasing in time.