METHOD AND APPARATUS FOR FOCUSED RESONANCE NANOPERMEABILIZATION (FORN)

• US 20120004591A1
• Filed: 03/16/2009
• Published: 01/05/2012
• Est. Priority Date: 03/16/2009
• Status: Active Grant

• Current Assignee: Rajah Vijay Kumar
• Original Assignee: Rajah Vijay Kumar
• Inventors: Kumar, Rajah Vijay
• Granted Patent: US 9,616,245 B2
• Time in Patent Office: Days
• US Class Current: 604/20
• CPC Class Codes: A61N 1/327 for enhancing the absorption properties of tissue, e.g. by electroporation
• CPC Class Codes: A61N 1/40 Applying electric fields by inductive or capacitive coupling microwave apparatus A61N5/00; Applying radio-frequency signals
• CPC Class Codes: A61N 2/004 specially adapted for a specific therapy
• CPC Class Codes: C12N 13/00 Treatment of microorganisms or enzymes with electrical or wave energy, e.g. magnetism, sonic waves

Abstract

This Invention relates to a method for achieving Focused Resonance Nanopermeabilization (FORN), which can be utilized in a novel anticancer therapy, and other selective permeabilization therapy and a machine to carryout the said method, where the transient permeabilization of cells by Focused Resonance pulses induces a significant increase of anti-tumor drug concentration in tumor or other interested cells. This invention can be successfully applied to the treatment of tumors in humans and Animals by using antimitotic drugs, chemotherapy. The invention is also useful in transpermeabilization of drug molecules for non cancer applications like vaccine and delivery of genetic materials for therapeutic purposes. Focused Resonance Nanopermeabilization (FORN), would enable a practical solution to a whole body application in its natural environment, without implanting electrodes or external probes, FORN is completely non-invasive. This invention also relates to an apparatus for carrying out the above method.

Claims

1. A method for achieving Focused Resonance Nanopermeabilization (FORN) which can be utilized in a novel anticancer therapy, immunization and drug prevention comprising the steps of

i. positioning a drug molecule around the cells generally in the interstitial space wherein the cell is covered with the intact cell membrane;

ii. delivering focused resonance radio frequency pulses to the tumor using specifically designed delivery system; and

iii. creating controlled resonance and beating it accurately so as to increase the difference in potential between membranes to a specific value and for a predetermined time interval sufficient to transport the interested molecule trough the temporary pathway and deliver to the tumor.

2. A method according to claim 1, including the steps of

a. Determining the type of cancer or other cells that needs to be permeated including collecting details such as:

i. the cell size;

ii. the cell radius or radii, in case of a set of cells; and

iii. the thickness of the cell wall, which is determined from a photo microgram prepared from the cell samples obtained during biopsy.

b. Selecting on the best possible drug that has to be permeated, including;

i. The molecular weight of the drug;

ii. peak plasma concentration;

iii. mode of delivery; and

iv. the dosage of the drug.

c. Preparing the “

Target Planning Films”

, derived from the 3D-PD sequence of MRI, that shows the core of the tumor mass and then positioning as many guns as required to be fired depending on the disease and the type of molecules to be permeated wherein a detailed treatment schedule is prepared by an expert, from the data obtained in step (a) such that the tumor is identified and marked on the Patient'"'"'s body under computer aided topography scanner guidance such that these marks are transferred onto a template for future use during the start of the FORN treatment.

3. A method according to claim 1, wherein the required dose of drug molecule is administered X-minutes before step ii of claim 1, where X represents peak plasma concentration of the drug to be administered followed by exposing the patient for Y-hours each day for Z-days, where Y is the half-life period of the drug and Z is the course or number of cycles of the drug, while performing periodic assessment using ultrasound or CT/MRI, wherein the machine is rolled in and the RF-guns are focused at the target using a laser-guided system.

4. A method of claim 1 wherein the most common molecules generally needed to be transpermeated are DNA, Protein, Antibodies, vaccines and heavy molecules for disease prevention especially in non-communicable diseases by obtaining beforehand parameters including:

i. Molecular weight;

ii. Peak plasma concentration;

iii. Washout time; and

iv. the proton density of the tissue to which transpermeation is required.

5. A method of claim 1 wherein the drugs administered are antimitotic drugs having the properties of (a) cytotoxicity and (b) non permeance and includes any molecule that has a therapeutic benefit.

6. An apparatus for achieving Focused Resonance Nanopermeabilization (FORN) which can be utilized as a novel anticancer therapy, immunization and drug prevention comprising:

a. A Gantry, which is a large tunnel like construction, housing special RFQMR delivery guns with near field antenna system;

b. A long table that holds the patient bed;

c. A Patient Transmission System housing located below the bed, which transports the patient into the bore of the gantry;

d. A back plane, which is the end part of the device;

it houses some of the safety devices; and

e. A Central Control Unit (CCU) that controls the entire operation of the Device comprised of two powerful Industrial Computers, two touch screen high performance LCD monitors, a video communication system and dose delivery monitors.

7. An apparatus of claim 6 wherein the patient transmission system (PTC) is a very important part of the device controls the movement of the bed, the speed of transport of patient, the direction of the bed movement and the control of laser guiding system, wherein the laser guide control is used for targeting the anatomical region of the patient that requires the treatment.

8. An apparatus of claim 6 wherein the patient transmission system (PTC) uses a variable frequency drive to control the speed of the movement of the bed into and out of the gantry including an emergency button that can be used in case of any malfunction of the transmission system.

9. An apparatus of claim 6 wherein the CCU comprises:

a. A Dose Delivery and Monitoring Computer (DMC), which is used to prepare the dosimetry for patients whose treatment has to be planned wherein the DMC can work independently from that of the other sub-assemblies on the CCU where the planning and preparation of dose will not effect the control of the gantry and thus does not effect the patient undergoing the treatment on the FORN Device;

b. A Gantry control computer (GCC), which is the main supervisory computer that controls all functions relating to the operation of the Gantry and all its guns. The GCC also handles communication between different axis and controls the delivered dose;

c. Dose Delivery Monitors (DDM), which indicate the delivered dose and firing of all guns wherein DDMs are divided into three sets each and is named “

Delivery X”

, “

Delivery Y” and

“

Delivery Z”

each of these being subdivided into axis A to Axis I wherein these DDMs also indicate if any of the guns in any of the axis is not firing; and

d. A Video Communication System (VCS) to communicate to the patient taking treatment inside the Gantry of the Cytotron device comprising a two way audio communication and one-way video communication system enabling the operator to monitor the patient continuously as well as give any instruction to the patients during the treatment time.

10. An apparatus of claim 6 comprising the critical mechanical components of:

i. Gantry Bore and Gun Assembly;

ii. Patient Transmission Assembly; and

iii. Bore and gun mounting assembly.

11. A system for achieving Focused Resonance Nanopermeabilization (FORN) which can be utilized in a novel anticancer therapy, immunization and disease prevention comprising:

i. A Supervisory Computer and control center;

ii. On-Board Computer for Axis Control System;

iii. High Current/High Voltage Power supply sub-assembly;

iv. Power Controller sub-assembly;

v. High speed switching sub-assembly called Gun Control;

vi. Patient Transport Control System;

vii. Laser Guiding and focus system;

viii. Delivery Guns with parabolic Antenna; and

ix. Cooling System.

12. A system of claim 11 wherein the Supervisory Computer and control center is the Master control of the entire system wherein all treatment related computation is done such that:

a. The system processes MRI information to obtain the Proton density of the tissue to be treated;

b. The required inputs like Molecular weight, Peak Plasma concentration, total washout time, tissue volume and the thickness of the cell membrane for computing the dosimetry is fed into this computer;

c. The supervisory computer and control center is connected to the on board Axis control computer and communicates via a RS232 communication protocol; and

d. The Supervisory Computer also keeps track of the patient'"'"'s data.

13. A system of claim 11 wherein the On-Board computer for Axis Control System further comprises (a) a Signal Modulator Sub-Assembly that is an important subunit of the On-Board computer and Axis Control System which receives multiple commands from the On-Board computer and Axis Control System and modulates them producing a unique Quantum RF Pulse that is supplied to the HSS sub-assembly for firing and (b) a field Rotator Sub-assembly that receives rotational information from the On-Board computer and Axis Control System and this is also an integral part of the On-Board Computer and sends it to the HSS sub-assembly for the control of field rotation, wherein the On-Board computer for Axis Control System further:

i. receives all information relating to the dose of the patient and controls all other sub-assemblies of the FORN system;

ii. contains all the necessary intelligence to takeover control if the Main control system fails during a treatment secession;

iii. controls the entire power controller and the switching sub-assemblies;

iv. receives the commands from the main computer pertaining to the dose such as resonant frequency, wave front frequency, spin frequency applied field strength, modulation details and the rate of change of the membrane potential required for a particular patient and his treatment schedule; and

v. computes and processes this data and transmits to other sub-assemblies for the smooth and coordinated operation of the entire system.

14. A system of claim 11 wherein the High Current/High Voltage Power supply (HCHV) is a sub-assembly that takes in the AC 230 volts power from the mains and converts into various high voltage low current as well as high current low voltage power sources for the operation of various sub-assemblies as well as the FORN guns and acts as the energy source for the entire system such that the power supply works in the switched mode and also provides excellent isolation, withstanding a dielectric breakdown in the order of 4 Kv.

15. A system of claim 11 wherein Power Controller sub-assembly receives the power from the HCHV power supply and controls the distribution of the same to the various other sub-assembly under the command and control of the On-Board computer and Axis Control System and further takes care of the safety aspects, like over loads, temperature or thermal shutdown etc. for the safe running of the system.

16. A system of claim 11 wherein High Speed Switching Sub-Assembly (HSS) receives multiple inputs from signal modulators, RF amplifiers and field rotators and operates under the command and control of the On-Board computer and Axis Control System such that the HSS sub-assembly is capable of handling high voltages and currents and switch them on and off at very high frequencies, thus is capable of producing fine modulated pulses of millionth of a second wherein this sub-assembly directly fires the QMR guns, under the instruction and regulation of the On-Board computer and Axis Control System.

17. A system of claim 11 wherein the Delivery Guns with parabolic Antenna are special antenna device made of high permeability material that produces high instantaneous magnetic field and RF pulses comprising:

i. three delivery systems known as “

delivery X”

, “

delivery Y”

, and “

delivery Z”

, each of these delivery systems consists of 3 axis totaling to 9 axis in total;

ii. the guns are accurately focused at the target tissue at the time of treatment; and

iii. independent switching devices drive these guns from the HSS sub-assembly.

18. A system of claim 11 wherein the Patient Transport Control System is that part of the machine that accurately positions the patients on the Bed inside the bore of the gantry of the FORN machine such that this sub-system consists of Motors, drives and gearbox for the purpose of smooth and efficient control.

19. A system of claim 11 wherein the Laser Guiding and focus system is used for focusing the emissions of the guns precisely to the effected part of the body wherein the patient gets a marking on the surface of the body under which the tissue to be treated is located such that the marking is done using the computerized tomography (CT) and the patient'"'"'s part of the body to be treated is placed inside the bore of the gantry of the FORN device and the Laser guides are turned on including final adjustments of the patient transmission system is done to obtain precise focusing.

20. A system of claim 11 wherein the Cooling System is intended to cool the machine so it functions within its operating temperature range such that temperature control is very important as the delivered signal can change its characteristics when there is a large temperature variation and the cooling system is based on heat conduction away from the source of the heat and a forced air cools the heat conduction system.

21. A system of claim 11 wherein the delivery of the desired molecule is delivered to target cells, cancerous or other vice using the novel technique of focused resonance nanopermeabilization within the natural environment of these cells.