This invention relates to apparatus for creating a magnetic field to externally propel a magnetic device within a matrix of material, such as a viscous medium in a biological tissue.
In many medical applications, it can be useful to have a miniaturized mobile device (herein denoted as a “bot”) to move in a medium such as found in a biological organism. For example, it may be desirable to move an internal device through tissue to a particular anatomic location to release a drug, gather diagnostic data, or conduct a remote-controlled surgical procedure. To facilitate such movement, propulsion and navigation utilizing magnetic fields has been developed.
One mode of propulsion involves applying an external uniform rotating magnetic field on internal device located inside the body. According to this mode, the internal device has a helical or a related shape (screw-like) exhibiting asymmetry and it comprises an embedded magnet with diametric magnetization. Rotating the external field exerts congruent rotational torque on the device, propelling it forward (like a screw). It is expected that reversing the external rotational field direction will yield a respective reverse particle dynamics. This propulsion method is denoted as “rotation.”
Another propulsion mode involves applying an external non-uniform magnetic field (a “magnetic gradient”) performing increasing strength along a controllable line (a “gradient line”) to an internal device located inside the body. The device includes an embedded magnet or a metallic component. In response to the external field gradient, the device moves along the gradient lines generated by the external magnet. This propulsion method is denoted as “gradient-based motion.”
A combination of the two above propulsion techniques are required to properly propel the bot through the tissue as each propulsion mode impacts the bot differently.
It is worth noting that the same magnetic system can be used to control other types of functionality of the bot remotely using a combination of magnetic field rotation and/or magnetic gradient, applied at a predefined time at a particular configuration, in parallel or separately from the propulsion of the bot. For example, in one embodiment the bot may contain an internal magneto-mechanic mechanism which extrudes a particular payload to the surrounding matrix in response to a predefined magnetic gradient or a predefined rotation of the external magnetic field generated by the magnetic system.
Various embodiments of the present invention provide external apparatus that establishes a variable magnetic field to manipulate a bot, for example, to propel a bot through a matrix of interest or to expel or deliver a payload from the bot into a matrix of interest. Such a matrix of interest includes, but is not limited to, a media, extracellular matrix, a compartment, tissue, organ, blood, lymph, biliary or cerebrospinal fluid in the region of the magnetic field.
The term “magnet” herein denotes any object having a magnetic field. In particular, a combination of individual magnets, including an “array” of individual magnets is herein itself considered a “magnet”. In some descriptions herein, a distinction is made between an “individual magnet” and an “array of magnets”, but it is understood that an “array of magnets” is also considered to be a “magnet”.
The term “propel” herein denotes the causing of any kind of physical motion, including, but not limited to: rotation, translation, vibration, oscillation, and combinations thereof.
The term “creating and manipulating a magnetic field” herein denotes making any changes to a magnetic field in a region, including, but not limited to: introducing a magnetic field into the region; moving a magnetic field from one place to another; and varying the intensity, flux, direction, and/or polarity of a magnetic field in the region.
According to certain embodiments, the external apparatus includes features such as:
An array according to a related embodiment is affixed, directly or indirectly, to a structural member, including but not limited to a platform, support, bracket, orienting apparatus, disk or other defined surface.
In another related embodiment, the magnet or array of magnets is attached to a mobility device having a motor to provide motion of the magnet or array, non-limiting examples of such motion including: rotation, cyclic motion (angular regular or irregular “rocking”; translational oscillation; and other such motion); vibration; trajectory motion (such as orbitally-circling a region); and combinations thereof.
As noted previously, a device according to various embodiments of the invention moves a bot via a torque, a linear force, and/or combinations thereof, wherein the torques and linear forces are applied via a magnetic field established by permanent magnets and arrays and/or electro-magnets which are prepared and arranged as disclosed herein.
According to certain embodiments, the function of torque applied to a bot is to overcome friction of the bot against surrounding media (such as diverse matrices, biological tissues and compartments) or other propulsion resistance forces, while the linear force propels the bot through the media itself. A rotating magnetic field perpendicular to the direction of bot motion provides torque on the bot, while a controlled gradient of that same field amplitude along the direction of desired bot motion, provides a linear attractive force on the bot.
According to an embodiment of the present invention, there is provided a system for creating and manipulating a magnetic field to propel a magnetic device in a specimen, the system comprising: (a) a cylindrically-disposed plurality of rod shaped or related magnets enclosing a hollow space to include the analyte, matrix, subject or specimen of interest, each rod magnet thereof having a transverse magnetization; (b) wherein the plurality of rod shaped or related magnets form an array including but not limited to a Halbach array which includes: (c) a first array of rod magnets; and (d) a second array of rod magnets; (e) wherein the first array of rod magnets and the second array of rod magnets are interleaved in an alternating fashion such that magnets from the first array always have magnets from the second array as their nearest neighbors; (f) and could be manipulated to: (g) alter positioning of all the magnets of the first array; and (h) alter positioning of all the magnets of the second array; (i) wherein the dynamics of the magnets of the first array is independent of the dynamics of the magnets of the second array.
In addition, according to another embodiment of the present invention, there is further provided a device for creating and manipulating a magnetic field to propel a magnetic device in a specimen including but not limited to an ex vivo matrix, biological specimen as exemplified by blood, lymph, bile, spinocerebral fluid, tissue, organ or compartment, the device comprising: (a) a magnet for creating the magnetic field; (b) a stage for holding the specimen; (c) support and orienting apparatus for the magnet, to which the magnet is attached; (d) support and orienting apparatus for the stage, to which the stage is attached; and (e) at least one positioning drive apparatus containing a motor; (f) controlling mechanism, wherein: (g) the support and orienting apparatus for the magnet includes at least a first rotatable offset bracket; and (h) the support and orienting apparatus for the stage includes at least a second rotatable offset bracket; (i) wherein the second rotatable offset bracket is rotated according to a position of the first rotatable offset bracket, so as to allow the first rotatable offset bracket to rotate to any angular position without having the magnet blocked by the second rotatable offset bracket, (j) such that the system is operative to orient the magnet over a solid angle of 4π steradians with respect to the stage.
In addition, so far as the embodiment of the previous device, in which the stage holding the specimen may also be placed inside the magnet and the magnet may therefore be rotated 4π steradians with respect to the stage.
The current embodiments of the invention have the current advantages: (a) Gradient to mediate reliable, reproducible motion at considerable distances, (b) Versatility in a combination with mechanical component: 2D/3D options, (c) Feasible size, safety, modular nature, applicability to studies of diverse matrices including animals, (c) Ability to accommodate i) diverse particles, ii) imaging, iii) delivery and retraction, iv) other (micro)devices used in (micro)manipulation including microsurgery, (d) Facile integration into a platform along with other modules.
The subject matter regarded as the invention is particularly pointed out and distinctly claimed herein. Embodiments of the invention, however, both as to organization and method of operation, together with objects, features, and advantages thereof, may best be understood by reference to the following detailed description when read with the accompanying drawings in which:
It will be appreciated that for simplicity and clarity of illustration, elements shown in the figures have not necessarily been drawn to scale. For example, the dimensions of some of the elements may be exaggerated relative to other elements for clarity. Further, where considered appropriate, reference numerals may be repeated among the figures to indicate corresponding or analogous elements.
In the following detailed description, numerous specific details are set forth in order to provide a thorough understanding of the invention. However, it will be understood by those skilled in the art that the present invention may be practiced without these specific details. In other instances, well-known methods, procedures, and components have not been described in detail so as not to obscure the present invention.
One of the key features provided by embodiments of the present invention is the ability to position magnet 401 at any desired location around a specimen, and to move magnet 401 continuously in any trajectory from that location to any other location. Mathematically, this requires being able to move magnet 401 continuously over a complete solid angle of 4π steradians. The described dynamics is accomplished by the apparatus shown in
In the following description, a system for positioning and orienting a magnet to propel a magnetic device in a specimen is described and illustrated for clarity in the specific case of a conical magnet. It is understood that this is a non-limiting example; in related embodiments, the same apparatus is used to position and orient other magnetic devices, including, but not limited to magnets of other shapes and having other field distributions, and arrays of magnets.
It is also contemplated that devices with a magnetic component for use in systems according to embodiments of the present invention will include devices described in International Patent Application PCT/US2018/030960 filed on May 3, 2018 and titled “METHODS AND SYSTEMS TO CONTROL PARTICLES AND IMPLANTABLE DEVICES,” which is hereby incorporated by reference in its entirety. Briefly, such devices with a magnetic component are microelectromechanical (MEM) devices, which comprise: (i) an actuator; (ii) a responsive element; (iii) a sensor; and (iv) an electronic circuit; wherein: said actuator controls and operates said responsive element; said electronic circuit controls said actuator; and said sensor receives signals transmitted by a remote unit. It is also contemplated that systems according to embodiments of the present invention will be included in the platforms described in International Patent Application PCT/US2018/030960. Briefly, such platforms comprise the following modules: (a) one or more devices with a magnetic component and comprising embedded logic and various MEM components; (b) a delivery and/or retraction module, configured to deliver and/or retract the devices; (c) an external signal generator; (d) an imaging module, configured to monitor said particles; and (e) an integration module configured to receive inputs from and to provide output control commands to other modules; wherein: said modules are configured to interact/communicate with each other; and said modules are internally controlled, externally controlled or both; and wherein said platform provides active, pre-determined, fully controlled, precise delivery of said devices in vitro, in vivo, and/or in a patient.
According to various embodiments of the present invention, offset brackets 503 and 508 provide support that is offset from vertical axis 505, and offset bracket 504 provides support that is offset from horizontal axis 515. This enables magnet 501 to be positioned directly in-line along both vertical axis 505 and horizontal axis 515, without interference from any supporting members that would block magnet 501 from being positioned as desired. In this manner, magnet 501 covers the full 4π steradian solid angle surrounding the specimen. According to these embodiments, the 4π steradian solid angle coverage is readily achieved by rotating offset bracket 508 so that it is always oriented 180° opposite to the rotated angular position of offset bracket 503. Meeting this orientation constraint guarantees that offset bracket 504 (to which magnet 501 is directly affixed) can be rotated to any angle around horizontal axis 515 without having magnet 501 blocked by offset bracket 508. In certain embodiments of the invention, offset bracket 508 is continuously rotated synchronously with respect to offset bracket 503 so that the above orientation constraint is always met; in other embodiments, however, offset bracket 508 is rotated only when necessary to avoid blocking magnet 501 by offset bracket 508.
The combination of magnet 501 with the above apparatus constitutes a system for creating and manipulating a magnetic field to propel a magnetic device in a specimen. The following discussion and drawings illustrate how such a combination can be constructed and used.
This application is a U.S. national stage application under 37 U.S.C. 371 of PCT International Application PCT/US2019/059096, filed Oct. 31, 2019, which claims benefit of U.S. Provisional Application No. 62/755,660 filed Nov. 5, 2018, the priority dates of which are hereby claimed, and the contents of each of which are hereby incorporated by reference in their entireties.
Filing Document | Filing Date | Country | Kind |
---|---|---|---|
PCT/US2019/059096 | 10/31/2019 | WO |
Publishing Document | Publishing Date | Country | Kind |
---|---|---|---|
WO2020/096855 | 5/14/2020 | WO | A |
Number | Name | Date | Kind |
---|---|---|---|
6876284 | Wright | Apr 2005 | B2 |
10539644 | Alarcon Herrera | Jan 2020 | B1 |
20030181788 | Yokoi et al. | Sep 2003 | A1 |
20040066107 | Gery | Apr 2004 | A1 |
20080097487 | Pool et al. | Apr 2008 | A1 |
20100217275 | Carmeli et al. | Aug 2010 | A1 |
20110215888 | Abbott et al. | Sep 2011 | A1 |
20120238796 | Conlon | Sep 2012 | A1 |
20130172672 | Iddan et al. | Jul 2013 | A1 |
20130245356 | Fernandez et al. | Sep 2013 | A1 |
20130289579 | Yeung et al. | Oct 2013 | A1 |
20130303847 | Sitti | Nov 2013 | A1 |
20140103765 | Post | Apr 2014 | A1 |
20140111202 | Wald | Apr 2014 | A1 |
20140187907 | Duan | Jul 2014 | A1 |
20140312716 | Hunter | Oct 2014 | A1 |
20150018615 | Duan | Jan 2015 | A1 |
20150177343 | Wald et al. | Jun 2015 | A1 |
20150374395 | Creighton | Dec 2015 | A1 |
20150380140 | Duan | Dec 2015 | A1 |
20180223481 | Dunham | Aug 2018 | A1 |
20210052190 | Kiselyov | Feb 2021 | A1 |
20210228298 | Qiu | Jul 2021 | A1 |
Number | Date | Country |
---|---|---|
2 196 131 | Jun 2010 | EP |
2 923 629 | Sep 2015 | EP |
3260259 | Sep 2020 | EP |
3411697 | Nov 2021 | EP |
2005-161052 | Jun 2005 | JP |
2013-108986 | Jun 2013 | JP |
2015-519175 | Jul 2015 | JP |
7429995 | Feb 2024 | JP |
WO-2007130634 | Nov 2007 | WO |
WO-2011029592 | Mar 2011 | WO |
WO-2011072060 | Jun 2011 | WO |
WO-2017134635 | Aug 2017 | WO |
WO-2018108850 | Jun 2018 | WO |
WO-2018187826 | Oct 2018 | WO |
WO-2018187826 | Oct 2018 | WO |
WO-2019005293 | Jan 2019 | WO |
WO-2019005293 | Jan 2019 | WO |
WO-2019213362 | Nov 2019 | WO |
Entry |
---|
Extended EP Search Report dated Mar. 7, 2022 in respect of EP Patent Application No. 19833954.1. |
Partial Supplementary Search Report dated Jul. 22, 2022 in respect of EP Patent App. No. 19881328.9. |
Extended EP Search Report dated Oct. 25, 2022 in respect of EP Patent Application No. 19881328.9. |
Office Action dated Aug. 9, 2022 in respect of JP Patent Application No. 2021-523489 (with English translation thereof). |
International Search Report dated Oct. 7, 2019 in respect of PCT Int'l Application No. PCT/US2019/041309. |
International Preliminary Report on Patentability dated Jan. 21, 2021 in respect of PCT Int'l Application No. PCT/US2019/041309. |
International Preliminary Report on Patentability dated May 20, 2021 in respect of PCT Int'l Application No. PCT/US2019/059096. |
Joshi, et al., “Circular Halbach array for fast magnetic separation of hyaluronan-expressing tissue progenitors”, Anal Chem. 2015, 87(19): pp. 9908-9915. |
International Search Report dated Mar. 18, 2020 from corresponding International Patent Application No. PCT/US19/59096. |
Number | Date | Country | |
---|---|---|---|
20210407717 A1 | Dec 2021 | US |
Number | Date | Country | |
---|---|---|---|
62755660 | Nov 2018 | US |