Batch-fabricated gradient glossary

• US 20030222648A1
• Filed: 06/02/2003
• Published: 12/04/2003
• Est. Priority Date: 06/03/2002
• Status: Active Grant

• Current Assignee: Long-Sheng Fan
• Original Assignee: Long-Sheng Fan
• Inventors: Fan, Long-Sheng
• Granted Patent: US 6,798,200 B2
• Time in Patent Office: Days
• US Class Current: 324/318
• CPC Class Codes: B82Y 15/00 Nanotechnology for interacting, sensing or actuating, e.g. quantum dots as markers in protein assays or molecular motors
• CPC Class Codes: G01R 33/302 Miniaturized sample handling arrangements for sampling small quantities, e.g. flow-through microfluidic NMR chips
• CPC Class Codes: G01R 33/5604 Microscopy; Zooming

Abstract

A batch micro-fabricable array of dimensionally scaled-down Integrated Micro Coil Structure (IMCS) having a plurality of multi-layer gradient coils and a set of RF coils is disclosed for Magnetic Resonance Imaging (MRI). The coil traces are made of electrically conductive material. The key scaled-down parameters include a maximum coil size of about 20 μm in diameter, a minimum layer thickness of about 20 μm, an analysis chamber size of 50 μm and an overall IMCS size of less than 10 mm. Coupled with an external MRI electronic driving and signal acquisition system, the IMCS functions to capture the three dimensional image of a magnetic nano article, located within the IMCS analysis chamber, with a high resolution of less than a μm. Also disclosed is a method of driving a small magnetic object having a magnetic moment, also located within the analysis chamber, by properly energizing the gradient coils.

Claims

1. A batch-fabricated array of dimensionally scaled-down Integrated Micro Coil Structure (IMCS) wherein each IMCS having a plurality of multi-layer gradient coils and a set of multi-layer Radio Frequency (RF) coils for high resolution Magnetic Resonance Imaging to capture the time evolution of a three dimensional image of an object, the IMCS comprising, expressed in an x-y-z Cartesian coordinate system:

an x-gradient coil set generating, when energized with an x-gradient coil current, a magnetic field B1 with a uniform x-gradient;

a y-gradient coil set co-located with said x-gradient coil set, said y-gradient coil set generating, when energized with a y-gradient coil current, a magnetic field B2 with a uniform y-gradient and substantially overlapping the uniform space of the said magnetic field B1;

a z-gradient coil set co-located with said x-gradient coil set and said y-gradient coil set, said z-gradient coil set generating, when energized with a z-gradient coil current, a magnetic field B3 with a z-gradient and substantially overlapping the uniform gradient space of said magnetic field B1 and said magnetic field B2 thus defining an analysis chamber being the spatial zone of overlapping of said uniform gradient space of said magnetic fields B1, B2 and B3;

an RF coil set for, when coupled with an external RF power driver and an external RF receiver, generating and introducing an RF excitation into said analysis chamber and detecting an RF signal emitted from said analysis chamber;

a shielding coil set for compensating magnetic field components to achieve a desired magnetic field pattern outside of said analysis chamber;

the coil traces of said x-, y- and z-gradient coil sets, said RF coil set and said shielding coil set being made of an electrically conductive material; and

where the key scaled-down geometric parameters having the following ranges;

a maximum wire size in the range of about 10 μ

m to 50 μ

m for said x-, y- and z-gradient coil sets, said RF coil set and said shielding coil set;

a minimum layer thickness of about 20 μ

m;

said analysis chamber size being in a range of about 25 μ

m to 100μ

m; and

the overall size, in terms of a maximum overall linear dimension, of said IMCS being less than or equal to about 10 mm.

2. The array of dimensionally scaled-down IMCS of claim 1 wherein said electrically conductive material for said coil traces being selected from the group consisting of Copper, Permalloy, Invar, Nickel and Gold.

3. The array of dimensionally scaled-down IMCS of claim 1 wherein the detailed geometry and orientation of said x-gradient coil set and said y-gradient coil set is a Golay coil.

4. The array of dimensionally scaled-down IMCS of claim 1 wherein the detailed geometry and orientation of said z-gradient coil set is a Helmholtz pair.

5. The array of dimensionally scaled-down IMCS of claim 1 wherein the detailed geometry and orientation of said RF coil set is an RF saddle coil.

6. The array of dimensionally scaled-down IMCS of claim 1 wherein the captured three dimensional image having a high spatial resolution, being equal to or less than a μ

m.

7. The array of dimensionally scaled-down IMCS of claim 1 wherein a highly uniform, within about 5%, high magnetic field gradient of at least about 10 T/m (Tesla per meter) is generated within said analysis chamber.

8. The array of dimensionally scaled-down IMCS of claim 1 wherein said x-, y- and z-gradient coil sets require only a low operating current of no more than an Ampere.

9. A method of batch microfabricating an array of dimensionally scaled-down IMCS wherein each IMCS having a maximum overall linear dimension of less than or equal to about 10 mm and having an x-gradient coil set, a y-gradient coil set and a z-gradient coil set expressed in an x-y-z Cartesian coordinate system and being spatially arranged to define an analysis chamber, which is coupled with a set of multi-layer RF coils and a shielding coil set for high resolution MRI wherein said x-, y- and z-gradient coil sets, said RF coil set and said shielding coil set having a maximum wire size in the range of about 10 μ

m to 50 μ

m comprising the steps of;

(a) making a cell-carrier plate with the following steps;

(a1) providing and passivating a substrate for electrical insulation;

(a2) forming, atop the passivated substrate, a metallic structure layer, destined to form a first coil of said z-gradient coil set and one part of return paths of said x- and y-gradient coil sets, by an electrochemical forming process into a photo-lithographically defined plating mold;

(a3) removing a plating seed layer associated with step (a2);

(a4) planarizing the top surface with a polymer layer and using Reactive Ion Etching (RIE), lapping or Chemical Mechanical Polishing (CMP);

(a5) depositing two etch stop layers till the complete formation of the main coil traces of said x- and y-gradient coil sets plus all their return paths and said RF coil set;

(a6) forming a return path of said RF coil set;

(a7) etching back said polymer layer with automatic stop at the first one of said two etch stop layers to form a number of alignment socket lips;

(a8) forming a cell-well with another etch process using a metal hard mask wherein the etch depth is defined by the second one of said two etch stop layers;

(a9) depositinga passivation layer that is Silicon Nitride, Silicon dioxide or polymer; and

(a10) plating and patterning a patterned thin solder layer on the top surface for later assembly;

(b) making a top cover plate with the following steps;

(b1) providing and passivating a substrate for electrical insulation;

(b2) forming, atop the passivated substrate, a metallic structure layer, destined to form a second coil of said z-gradient coil set and the other part of the return paths of said x- and y-gradient coil sets, by an electrochemical forming process into a photo-lithographically defined plating mold;

(b3) removing a plating seed layer associated with step (b2);

(b4) planarizing the top surface using RIE, lapping or CMP;

(b5) repeating steps (b2) through (b4) till the complete formation of the main coil traces of said x- and y-gradient coil sets plus all their return paths and said RF coil set;

(b6) forming the return paths of said x- and y-gradient coil sets;

(b7) plating and patterning a patterned thin solder layer, with a pattern matching that of step (a10), on the top surface for later assembly;

(b8) etching a central opening using a thin-film metal hard mask through the substrate;

(b9) removing said thin-film metal hard mask; and

(b10) depositing a passivation layer that is Silicon Nitride, Silicon dioxide or polymer; and

(c) assembling said cell-carrier plate with said top cover plate with the following steps;

(c1) flipping the top cover plate from step (b) and aligning the flipped top cover plate to the cell-carrier plate from step (a);

(c2) bonding the aligned top cover plate and cell-carrier plate together using a self-aligned solder reflow process predicated upon the matching thin solder patterns of steps (a10) and (b7); and

(c3) removing, as an option, the substrate of the top cover plate for easy access.

10. The method of batch microfabricating an array of dimensionally scaled-down IMCS of claim 9 wherein said substrate is made of glass, alumina or other ceramics.

11. The method of batch microfabricating an array of dimensionally scaled-down IMCS of claim 9 further comprising making an injection molded thin micro plate, and sandwiching said thin micro plate between said cell-carrier plate and said top cover plate before step (c).

12. The method of batch microfabricating an array of dimensionally scaled-down IMCS of claim 9 wherein said steps (a1) and (b1) employ Silicon Nitride, Silicon dioxide or polyme for electrical insulation.

13. The method of batch microfabricating an array of dimensionally scaled-down IMCS of claim 9 wherein said passivation layer of steps (a9) and (b10) is formed by Plasma-Enhanced Chemical Vapor Deposition (PECVD).

15. The driving method of claim 9 further comprising a preparatory magnetic labeling step of binding a target non-magnetic object with a magnetic carrier having a magnetic moment to form said small magnetic object such that said target non-magnetic object is indirectly driven via said small magnetic object.

16. The driving method of claim 10 wherein said magnetic carrier is a magnetic nano particle.

17. The driving method of claim 11 wherein said magnetic nano particle is a ferritesuper-paramagnetic particle.

18. The driving method of claim 10 wherein said target non-magnetic object is a biomolecule or a collection of biomolecules.

19. The driving method of claim 13 wherein said biomolecules are oligos, aptomers or antibodies.

14. A method of driving, causing a corresponding trajectory of movement, a small magnetic object having a magnetic moment and being disposed within a dimensionally scaled-down IMCS wherein each IMCS wherein each IMCS having a maximum overall linear dimension of less than or equal to about 10 mm and having an x-gradient coil set, a y-gradient coil set and a z-gradient coil set expressed in an x-y-z Cartesian coordinate system and being spatially arranged to define an analysis chamber, which is coupled with a set of multi-layer RF coils and a shielding coil set for high resolution MRI wherein said x-, y- and z-gradient coil sets, said RF coil set and said shielding coil set having a maximum wire size in the range of about 10 μ

m to 50 μ

m, comprising the steps of

(a) introducing a small magnetic object within said analysis chamber;

(b) for an x-component force, if desired, energizing said x-gradient coil set with a pre-determined polarity and amount of x-gradient coil current thus generating a magnetic field Bz1 with an x-gradient causing said x-component force, being proportional to said x-gradient, to be exerted on said magnetic object;

(c) for a y-component force, if desired, energizing said y-gradient coil set with a pre-determined polarity and amount of y-gradient coil current thus generating a magnetic field Bz2 with a y-gradient causing said y-component force, being proportional to said y-gradient, to be exerted on said magnetic object; and

(d) for a z-component force, if desired, energizing said z-gradient coil set with a pre-determined polarity and amount of z-gradient coil current thus generating a magnetic field Bz3 with a z-gradient causing said z-component force, being proportional to said z-gradient, to be exerted on said magnetic object.