Protease-Activated Fluorescence Probe for Tumor Margin Detection
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Solution Overview
Problem
Conventional intra-operative imaging techniques lack the necessary resolution and precision to accurately differentiate between scar tissue and diseased tissue, leading to incomplete removal of abnormal cells during surgical resections, particularly in cases like malignant gliomas and heart arrhythmias, due to limitations in imaging agents and systemic administration methods.
Innovation Solution
A topical protease-specific, fluorescence imaging probe that is activatable by enzymatic activation, allowing for precise detection of cancer cells by producing a visually differentiated signal upon interaction with enzymes like Cathepsin B and Cathepsin L, enabling accurate identification and targeting of tumor margins during surgery.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional intra-operative imaging techniques are used, then surgical guidance is provided, but resolution is insufficient (approximately 0.9 mm) to differentiate scar tissue from diseased tissue
Solution Approach 1:
The patent introduces molecular probes as intermediary agents that bind to specific molecular targets in diseased tissue. These probes act as mediators between the imaging system and the tissue, enabling detection at the molecular level rather than relying solely on anatomical resolution. The probes convert molecular information into detectable signals, allowing differentiation of diseased tissue from scar tissue even when anatomical structures appear similar.
Solution Approach 2:
The patent changes the detection parameter from anatomical structures (visible at 0.9 mm resolution) to molecular targets (detectable at much smaller scales). By using probes that bind to specific molecules overexpressed in diseased tissue, the system transitions from detecting tissue morphology to detecting molecular composition, effectively bypassing the resolution limitation of conventional imaging.
2Area of stationary object
If systemic administration of imaging agents is used, then tissue coverage is achieved, but dose requirements become unacceptable and translation from clinical trial is expensive and labor intensive
Solution Approach 1:
The patent employs probes with localized binding properties that concentrate imaging activity at the surgical site where molecular targets are present. Rather than requiring systemic distribution throughout the entire body, the probes are administered locally or systemically at low doses and accumulate preferentially at the tumor margin through specific molecular binding, achieving effective tissue coverage only where needed.
Solution Approach 2:
The patent replaces the mechanical approach of high-dose systemic flooding with a molecular recognition system. Instead of relying on bulk distribution and high concentration throughout the body, the system uses specific molecular interactions to achieve targeted accumulation, substituting non-specific mechanical distribution with specific biochemical recognition.
3Illumination intensity
If conventional imaging agents are used, then signal detection is possible, but background auto-fluorescence from the patient creates significant interference making unambiguous detection problematic
Solution Approach 1:
The patent utilizes fluorescent probes that emit light at specific wavelengths distinct from the background auto-fluorescence spectrum. By selecting probes with emission wavelengths in regions where biological tissue has minimal intrinsic fluorescence (such as the near-infrared window), the system achieves spectral separation between the probe signal and background, enabling clear distinction and unambiguous detection.
4Productivity
If surgical excision is performed without molecular imaging guidance, then surgery can be completed, but malignant cells at tumor margins may be left behind resulting in incomplete resection
Solution Approach 1:
The patent implements real-time feedback during surgery by using molecular probes that provide immediate visual or signal-based information about the presence of diseased tissue at the resection margin. As the surgeon removes tissue, the probe continuously indicates whether malignant cells remain, allowing dynamic adjustment of the resection boundary to ensure complete removal while preserving healthy tissue.
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 system enables precise detection of tumor margins and infiltrating cancer cells, facilitating more effective surgical resections and reducing the need for systemic administration of imaging agents, thereby improving surgical outcomes and reducing tissue damage.
Implementation Method 1
A topical protease-specific, fluorescence imaging probe that is activatable by enzymatic activation
Implementation Method 2
fluorescence imaging probe that is activatable by enzymatic activation to produce a visually differentiated signal
Data Source
AI summary
A system for detecting tumor margins includes a topical protease-specific, fluorescence imaging probe that is activatable by enzymatic activation to produce a visually differentiated signal upon topical application to a targeted cancer cell that secretes an enzyme that activates the protease-specific, fluorescence imaging probe, an applicator for topically administering the imaging probe to the cancer cell; and an imaging device to detect activation of the imaging probe administered to the cancer cell.