Photothermal Cargo Delivery into Live Cells Using Transient Cavitation
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Solution Overview
Problem
Existing methods for delivering cargo into mammalian cells, such as proteins, DNA, and organelles, face challenges including low efficiency, toxicity, limited cargo size, and cell-type specificity, with mechanical and thermal methods causing membrane trauma and inefficiencies in large cargo delivery.
Innovation Solution
The use of photothermal platforms with porous membranes and micro-orifices coated with materials like titanium that heat up under optical radiation, forming cavitation bubbles to transiently open cell membranes for efficient cargo delivery.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If mechanical penetration methods (microcapillary injection) are used to deliver cargo into cells, then delivery precision is improved, but cell viability deteriorates due to membrane trauma and the method is limited to small cargo sizes
Solution Approach 1:
The patent replaces mechanical penetration methods with a photothermal method using laser-induced cavitation bubbles. The laser heats a photothermal agent (e.g., gold nanoparticle, carbon nanoparticle, or iron oxide nanoparticle) localized at the target site, generating a cavitation bubble that mechanically disrupts the cell membrane to create a pore for cargo delivery, avoiding direct mechanical trauma from pipette penetration.
Solution Approach 2:
The patent introduces a photothermal agent (intermediary material such as gold nanoparticle, carbon nanoparticle, or iron oxide nanoparticle) that absorbs laser energy and converts it to thermal energy, generating the cavitation bubble. This intermediary enables indirect mechanical disruption of the cell membrane without direct contact from mechanical instruments.
2Volume of moving object
If pore size is increased to deliver large cargo, then cargo delivery capability is improved, but cell viability deteriorates due to excessive membrane damage
Solution Approach 1:
The patent creates a dynamic, transient pore through laser-induced cavitation that opens briefly to allow cargo entry then closes automatically. The pore exists only during the cavitation bubble formation and collapse (microseconds to milliseconds), providing temporary access for large cargo while minimizing lasting membrane damage and maintaining cell viability.
Solution Approach 2:
The patent uses pulsed laser irradiation to create periodic cavitation bubbles at controlled intervals. Each pulse generates a transient pore that opens and closes rapidly, allowing repeated opportunities for cargo delivery while limiting total exposure time and cumulative membrane trauma, thereby maintaining cell viability even when delivering large cargo.
3Productivity
If electroporation methods are used to create pores for cargo delivery, then delivery efficiency is improved, but the method produces randomly distributed pores and has limited control over pore location and size
Solution Approach 1:
The patent applies photothermal heating locally at the target site by focusing laser energy on a photothermal agent positioned at the desired location. This creates a localized cavitation bubble and pore precisely where needed, enabling controlled pore location, size, and timing without random distribution, while maintaining high delivery efficiency.
Solution Approach 2:
The patent controls pore characteristics (location, size, duration) by adjusting laser parameters (power, pulse duration, wavelength) and photothermal agent properties (concentration, size, composition). This provides precise control over pore formation parameters, enabling tailored delivery conditions for different cargo types and cell types while maintaining high efficiency.
4Quantity of substance
If viral or chemical delivery methods are used, then cargo packaging capacity is improved, but toxicity and cell-type specific uptake limit applicability
Solution Approach 1:
The patent employs a universal photothermal delivery platform that can deliver diverse cargo types (small molecules, proteins, nucleic acids, organelles, cells) across different cell types without requiring cargo-specific viral vectors or chemical formulations. The laser-induced cavitation mechanism is broadly applicable and not limited by cargo properties or cell-type specificity, providing universal delivery capability.
Solution Approach 2:
The patent replaces biological (viral) and chemical delivery systems with a physical photothermal method using laser-induced cavitation. This eliminates toxicity associated with viral vectors and chemical transfection reagents, while the mechanical cavitation force can accommodate any cargo size without the packing capacity limitations of viral vectors, greatly expanding versatility.
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 method enables high-throughput delivery of various cargos, including large particles and organelles, with maintained cell viability and broad applicability across cell types, achieving efficient and rapid delivery to multiple cells simultaneously.
Implementation Method 1
a thin film coating a material that heats up when exposed to optical radiation
Implementation Method 2
forming cavitation bubbles to transiently open cell membranes
Data Source
AI summary
Methods, devices, and systems are provided for the delivery of agents (e.g., nucleic acids, proteins, organic molecules, organelles, antibodies or other ligands, etc.) into live cells and/or the extraction of the same from said cells. In various embodiments the photothermal platforms and systems incorporating such photothermal platforms are provided that permit efficient, high-throughput cargo delivery into live cells.