Invented by Edward R. Flynn, Senior Scientific LLC
The Senior Scientific LLC invention works as followsThe present invention provides methods for detecting, locating, or measuring cells or substances in very low concentrations, in vivo, in subjects using magnetic nanoparticles. Magnetizing subsystems can be combined with sensors subsystems. Examples include SQUID sensors or atomic magnetometers. The magnetic systems are able to detect, measure or locate particles bound by antibodies with cells or substances that have been predetermined. Magnetic systems can detect nanoparticles in sub-nanogram quantities.
Background for Detection and measurement of cells, such as cancer, and other biological substances using magnetic properties and targeted nanoparticles
Early detection of disease increases the chances of a successful recovery and treatment. Early detection and localization allows for targeted therapy at the site of disease, optimizing treatment efficiency. With the use of a suitable detection device, treatment can be monitored to increase the effectiveness of drugs or other forms therapy. Treatment outcomes can be improved by targeting specific diseases. Cancer, the second-leading cause of death in America, can be detected early and treated more effectively. All of the most common methods for cancer detection are non-specific. They cannot differentiate between cancerous and benign tumors, nor can they provide 100% accuracy. All the methods have their own weaknesses and disadvantages, which can lead to a high rate of false diagnoses, and a low rate of positive diagnoses, leading to an increased mortality rate. “The most common clinical modalities available today are (1) X-ray Mammography, (2) Magnetic Resonance Imaging (MRI), (3) Ultrasound scanning and (4) Positron-Emission Tomography (PET) as an option.
The FDA has approved this device, which is the most commonly used tool to detect cancer and other diseases. This is responsible for many false negative and false positive results. Cancer tumors in the early stages can be detected, but without specificity as to whether they are cancerous or benign. Healthy tissue can cause artifacts and false positive results. The exposure to radiation and X-rays is of increasing concern, even though the dose is very low. The number of false-positives in x ray imaging of cancer is high, and the method cannot detect early-stage tumours.
Ultrasound can be used as a second imaging method. The spatial resolution of ultrasound is lower than that of x-rays or other imaging methods. The FDA has not approved ultrasound as a primary cancer screening tool. However, it is used to follow-up on abnormalities found during routine. It is often used to confirm suspicious areas on x-rays of breast and ovarian carcinoma.
MRI can be used to monitor potential problem areas that were seen in x-rays. However, the cost of an MRI scan is often prohibitive. MRI is useful for detecting small abnormalities and determining if a cancer has spread. The Dynamic Contrast Enhanced MRI (DCE) can distinguish between cancerous and benign tumors, but it also produces a lot of false positives. The cost of MRI makes it less useful as a screening method. MRI imaging for cancer is often done using magnetic nanoparticles. This protocol provides standards for the injection. “Intravascular MRI contrast agents have been used at a dose 2 mg/kg nanoparticle weight to detect metastatic lesions.
There are many other imaging techniques being investigated because of the importance early detection. Scintimammography with PET or SPECT is one of the techniques being studied. Others include Impedance Tomography and other forms of RF Imaging.
Early detection is critical, as many cancers that are detected early can be cured. Often, existing imaging methods do not detect lesions until they have grown significantly. Research is being conducted on alternative methods such as MRI, PET scans, ultrasound, scintigraphy and others. Currently, none of the methods can differentiate between cancerous tissue and non-cancerous tissues based on differences in tissue properties. A new method that does not require radiation or expensive procedures and can detect tumors very early is needed. The present invention offers new capabilities for cancer detection in-vivo.
DISCLOSURE of INVENTION
This application is related with the following applications. Each of them is incorporated by reference herein: U.S. “This application is related to the following applications, each of which is incorporated herein by reference: U.S. 61/259,011 filed 6 Nov. 2009; 61/308,897 filed 27 Feb. 2010; and 61/314,392 filed 16 Mar. Each of which are incorporated by reference.
The present invention provides devices and methods for detecting cells or substances, such as cancerous cells in tissue. The system includes a magnetic system that comprises a magnetic generator that applies a known magnetic fields to tissue of a subject, magnetizing paramagnetic particles bound to cells or substances of interest, and a sensitive magnet sensor that detects the residual magnetic field when the magnetization of nanoparticles decreases. A magnetic system example comprises a superconducting quanta interference device sensor that includes a magnetic pulser adapted to apply an uniform magnetizing pulse to cancer tissue of a subject placed on a measuring stage, and a remnant field detector adapted for detecting and imaging the residual magnetic fields produced by the pulsed field. The magnetic pulser may consist of a pair Helmholtz coils. The remnant magnetic detector can be an array of gradiometers. A second example of a magnetic system includes an atomic magnetometer, and an array gradiometers. These are very sensitive magnetic field sensors which can be used to detect extremely weak magnetic fields using the Larmor Precession of atoms within a magnetic field. In certain embodiments, the atomic magnometer is a chip set that contains a small cavity with an atomic vapour cell. This vapor cells contains Rb atoms and is optically pump by circularly-polarized laser beam. The atoms undergo a Larmor Precession, and the frequency of that precession changes the index of reflection of the vapor when a magnetic field is applied. The second laser can act as a measuring field to determine the change in refraction by using a set gratings that measure the interference patterns as the magnetic field changes. The vapor cell can be arranged as a gradiometer to measure changes in the field as a function distance.
The present invention describes a method that involves providing a magnetic system, injecting a number of paramagnetic (e.g. labeled) nanoparticles for binding specifically to cancer cells, or other cells, or substances of interest, applying a known magnetizing pulse to magnetize the particles in the subject tissue, and then detecting the residual magnetized field of the magnetized microparticles to provide an image of nanoparticles bound with the cancer tissue of a patient. The magnetic nanoparticle that is targeted can be a magnetic core with a biocompatible surface to which at least one antibody has been attached. The magnetic core, for example, can be made of a ferromagnetic substance, such as iron dioxide. Below are some examples of targeting agents, such as antibodies.
BRIEF DESCRIPTION DES DRAWINGS
The accompanying drawings are part of and incorporated into the specification. They illustrate the invention, and together with the description describe it. “In the drawings, similar elements are referred by like numbers.
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