Nanoparticle DNA Barcode Screening for Cell Tracking
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Solution Overview
Problem
Current high-throughput cell screening methods face limitations such as the need for preliminary ordering and tracking of candidate molecules, difficulty in analyzing suspended or 3D cell cultures, and challenges in tracking and recovering cells, especially when using viral vectors which can interfere with RNA interference processes and induce phenotype modifications.
Innovation Solution
A method using nanoparticles less than 1 micron in size, preferably less than 200 nm, with a positive charge for efficient cell penetration, delivering a candidate molecule, a tracer for tracking, and a single DNA tag for identification, allowing for the simultaneous delivery and post-readout identification of molecules of interest without preliminary ordering, suitable for screening biomarkers and phenotypic traits.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If plate or chip based high-throughput screening is used, then screening throughput is improved, but preliminary ordering and tracking of candidate molecules is required which increases complexity
Solution Approach 1:
The patent uses DNA barcodes as information copies that are attached to candidate molecules. Instead of tracking physical molecules through ordering systems, the DNA barcode serves as an information carrier that can be read and identified, eliminating the need for complex preliminary ordering and tracking infrastructure while maintaining high throughput screening capability
Solution Approach 2:
The patent introduces DNA barcodes as an intermediary between the candidate molecules and the screening system. These barcodes serve as mediators that carry identification information, allowing the screening system to identify molecules without requiring complex tracking infrastructure, thus resolving the contradiction between throughput and complexity
2Reliability
If viral vectors are used for delivering candidate molecules, then delivery efficiency is improved, but interference with RNA interference processes and induction of phenotype modifications occurs
Solution Approach 1:
The patent uses nanoparticles as disposable delivery vehicles that can be synthesized, functionalized with DNA barcodes and candidate molecules, used for delivery, and then discarded. These nanoparticles do not integrate into the genome or persist long-term, avoiding the harmful effects of viral vectors while maintaining delivery efficiency
Solution Approach 2:
The patent introduces nanoparticles as an intermediary delivery system between the candidate molecules and the cells. These nanoparticles serve as neutral mediators that deliver the therapeutic payload without the biological activity that causes RNA interference interference or phenotype modifications associated with viral vectors
3Loss of information
If cells are marked for tracking before screening, then cell tracking is improved, but the marking may alter the efficiency of candidate molecules
Solution Approach 1:
The patent segments the tracking function from the candidate molecule itself by attaching DNA barcodes to the nanoparticles that carry the molecules. The tracking information is separated into the DNA barcode component, while the candidate molecule retains its full biological activity without interference from marking elements
Solution Approach 2:
The patent uses DNA barcodes as information copies that are attached to the nanoparticles carrying candidate molecules. These barcodes provide tracking information without physically modifying the candidate molecules themselves, thus preserving molecule efficiency while enabling tracking
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 high-throughput screening at the individual cell level with efficient sorting and identification of candidate molecules, overcoming limitations of traditional methods by allowing direct delivery and tracking within cells, and avoiding interference with RNA interference processes.
Implementation Method 1
nanoparticles less than 1 micron in size, preferably less than 200 nm, with a positive charge for efficient cell penetration
Data Source
AI summary
The present invention relates to a method for screening a molecule of interest by means of nanoparticles comprising a candidate molecule, a tracer, and a single DNA tag specific to said molecule. The present invention also relates to a method for screening biomarkers of a disease and/or of a phenotype feature, more particularly of a cancer or an infection, by means of said nanoparticles. The invention finally relates to the nanoparticles as such as well as to a library of said nanoparticles.