DNA Origami Cell Sensing Platform for Real-Time Biomolecule Detection
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Solution Overview
Problem
Current methods for monitoring cell interactions with extracellular signaling molecules in 3-D tissue environments lack real-time, spatiotemporal resolution and cannot detect multiple biomolecules simultaneously, limiting understanding of cell biology and therapeutic development.
Innovation Solution
A DNA origami Cell Sensing Platform (CSP) is integrated into cell membranes, using planar nucleic acid nanostructures with membrane anchoring moieties and sensor molecules to detect specific target molecules, enabling real-time monitoring of multiple biomolecules in a 3-D microfluidic tissue model.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional methods are used for monitoring cell interactions, then the monitoring can be performed, but real-time spatiotemporal resolution and simultaneous detection of multiple biomolecules cannot be achieved
Solution Approach 1:
The patent integrates multiple sensor molecules onto a single cell membrane, enabling the system to detect multiple different biomolecules simultaneously. Each sensor molecule is designed to bind a specific target, and the combination provides multi-functional detection capability while maintaining real-time monitoring through the fluorescent reporter system
Solution Approach 2:
The patent employs fluorescent reporter molecules that emit different wavelengths of light when bound to different target molecules. This optical signal variation enables simultaneous detection of multiple biomolecules with high spatiotemporal resolution, as each fluorescent signal can be distinguished by its wavelength
2Productivity
If sensor molecules are integrated into cell membranes, then real-time detection capability is improved, but the complexity of the sensing platform increases
Solution Approach 1:
The sensing platform is divided into discrete sensor molecules, each comprising a sensor domain, reporter domain, and linker. This modular segmentation allows for systematic integration of multiple sensors onto the cell membrane while maintaining organized structure and facilitating real-time detection of multiple targets simultaneously
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 CSP allows for robust, real-time detection of multiple biomolecules on cell membranes with subcellular resolution, enhancing the understanding of cell interactions and disease mechanisms, and facilitating the development of effective therapeutics.
Implementation Method 1
the second strand has a donor fluorophore that is quenched by the quencher fluorophore in the absence of a target molecule, wherein binding of the first strand to the target molecule displaces the quencher fluorophore from the donor fluorophore
Implementation Method 2
the membrane anchoring moiety has a hydrophobic anchor, such as a cholesterol
Data Source
AI summary
Disclosed herein a robust approach to monitor cell interactions with its surrounding environment in real-time in a physiologically relevant 3-D microenvironment, holding great promise for enhancing future studies of detecting and monitoring cell processes and responses to instructive cues and therapeutic agents. A microfluidic cell culture system is provided that involves a cell sensor in a 3D culture scaffold and one or more microfluidic channels fluidly connected to the 3D culture matrix. The cell sensor involves a planar nucleic acid nanostructure having a top surface and a bottom surface, a plurality sensor molecule attached to the top surface to detect at least two target molecules, and one or more membrane anchoring moieties attached to the bottom surface.