Systems, devices, and methods for electroporation induced by magnetic fields
Inventors
PIHL, CHRISTOPHER JAMES • Scholz, Matthew Rein • Kirtley, David Edwin
Assignees
Publication Number
US-11442117-B2
Publication Date
2022-09-13
Expiration Date
2037-11-09
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Abstract
A system includes a control device and a magnetic device coupled to the control device. The magnetic device is configured to inductively couple to a treatment target including one or more cells exposed to an agent, and includes one or more magnetic coils. The control device and the magnetic device are collectively configured to generate and apply a transient magnetic field to the treatment target to induce an electric field and porate the one or more cells and to permit the agent to enter the one or more cells.
Core Innovation
The invention provides systems, devices, and methods for porating biological cells using transient magnetic fields to induce electric fields within a treatment target. A system includes a control device and one or more magnetic devices, each comprising magnetic coils, configured to magnetically couple to a treatment target containing cells exposed to an agent. The control device and magnetic device generate and apply a transient magnetic field to porate the cells, allowing the agent to enter the cells.
The problem being solved addresses the shortcomings of traditional electroporation, such as the tradeoff between effective reversible poration and undesirable cell death due to current flowing between electrodes through the medium. Traditional methods also suffer from field enhancements caused by electrodes, nonhomogeneous geometries, arcing due to bubbles or salts, invasiveness and pain in vivo from electrode penetration, and poor electroporation efficiency with impure nucleic acid preparations or high salt concentrations.
The invention overcomes these issues by using magnetically induced transient fields that generate electric fields within the sample, enabling poration without the need for direct electrode contact or current flow through electrodes. The method allows for reversible or irreversible poration and can treat various volumes by adjusting coil geometry and electrical signals. The system can include multiple independently addressable magnetic coils and circuits to provide tailored spatial and temporal magnetic field application to the target. The use of inductors and ferromagnetic cores can further enhance transient electric fields and poration efficiency.
Claims Coverage
The claims include one independent system claim and one independent method claim. These claims cover inventive features related to generating and applying transient magnetic fields using multiple independently addressable magnetic devices to porate cells and permit agent entry.
System with independently addressable magnetic devices and circuits
A system comprising a control device with multiple independent circuits and a set of magnetic devices magnetically or inductively coupled to a treatment target with cells exposed to an agent. Each magnetic device includes one or more magnetic coils and is independently addressable by a corresponding circuit. The system includes a user interface to receive spatial information, and collectively generates and applies transient magnetic fields based on this spatial information to porate cells and allow agent entry.
Transient magnetic fields inducing electric fields to porate cells
The transient magnetic fields generated by the system are configured to induce electric fields in the treatment target to porate the cells, with magnetic coils positioned in proximity to at least a portion of the treatment target during use.
Signal generator producing various electrical waveforms
The control device includes a signal generator configured to apply electrical signals to each magnetic device. The signal generator can be an oscillator, frequency synthesizer, sine-wave generator, pulse generator, random noise generator, arbitrary waveform generator, or combinations thereof. The electrical signal can be a pulsed ¼ sine wave followed by an L/R decay, a sine wave, decaying sine wave, square wave, or arbitrary waveform.
Magnetic devices comprising ferromagnetic elements or superconducting electromagnets
Each magnetic device can include a ferromagnetic circuit element acting as an inductor or a superconducting electromagnet configured to generate transient magnetic fields.
Magnetic coils configured as oscillating antennae
The magnetic coils can be one or more oscillating antennae, each independently addressable.
Transient magnetic fields defining treatment volumes
The set of transient magnetic fields defines a treatment volume of at least about 10 microliters.
Reversible or irreversible poration configuration
The transient magnetic fields are configured to porate cells reversibly or irreversibly to permit the agent to enter the cells.
Treatment target variety and cell types
The treatment target can be a container, medical device, or mammalian target with cells in vitro, in vivo, or ex vivo. The cells include mammalian cells (various tissue types), bacterial, fungal, parasitic, or plant cells.
Agents introduced into cells
The agent can be a nucleic acid, a polypeptide (including enzymes, ligands, receptors, antigens, antibodies or fragments), a conjugated drug or molecule (e.g., radioimmunotherapy, antibody-drug conjugate), or a small molecule drug.
Method of porating cells with spatially informed transient magnetic fields
A method comprising exposing cells in a treatment target to an agent, receiving spatial information, and applying a set of transient magnetic fields based on the spatial information to porate the cells and permit agent entry.
The claims collectively cover systems and methods that utilize multiple independently addressable magnetic coils driven by independent circuits under spatial control to generate transient magnetic fields that induce electric fields in treatment targets, thereby porating cells and facilitating agent entry. The claims include varied forms of magnetic devices, signal generators, target types, cell types, and agents.
Stated Advantages
Magnetoporation does not use electrodes, producing a smooth field that induces uniform current without highly ionized paths, reducing arcing and associated cell death.
The method allows precise control to maximize efficiency with minimal cell death and less pain compared to electrode-based in vivo electroporation.
It is scalable to treat small or large volumes, showing superior current uniformity and distribution, inherent arc suppression, and no contamination risk from electrodes.
The system can selectively target cell types like skeletal muscle, enhancing protein production due to long-lived myocytes.
The process can be controlled with greater precision than traditional electroporation methods.
Documented Applications
Treating infections.
Treating cancer.
Performing gene therapy.
Producing polypeptides.
Treating or correcting hereditary disorders such as cystic fibrosis, Down Syndrome, autoimmune diseases, muscular dystrophy, hemophilia, and sickle cell anemia.
Ex vivo or in vivo modification of cells for vaccination-like applications, including introducing exogenous agents into immune cells like B cells, T cells, or antigen-presenting cells.
Ex vivo protein production and altering trafficking of cells or exosomes for therapeutics.
Poration of blood cells, including red blood cells for transport across the blood-brain barrier.
Genome engineering with reduced tissue damage compared to electroporation and enhanced delivery of constructs like CRISPR.
Immunotherapy, including cancer immunotherapy by introducing constructs that alter tumor immunomodulatory environments or induce apoptosis.
Altering non-endogenous cells such as CHO cells, yeast, bacteria, or parasites.
Agricultural applications for crop and plant cell modification.
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