Guided transport of magnetically labeled biological molecules and cells

Patent metadata

Field	Value
Publication number	US-9656271-B2
Application number	US-99917107-A
Country	US
Kind code	B2
Filing date	Dec 4, 2007
Priority date	Dec 4, 2007
Publication date	May 23, 2017
Grant date	May 23, 2017

Abstract

Presented herein is a method and devices for identifying biological molecules and cells labeled by small magnetic particles and by optically active dyes. The labeled molecules are typically presented in a biological fluid but are then magnetically guided into narrow channels by a sequential process of magnetically trapping and releasing the magnetic labels that is implemented by sequential synchronized reversing the magnetic fields of a regular array of patterned magnetic devices that exert forces on the magnetic particles. These devices, which may be bonded to a substrate, can be formed as parallel magnetic strips adjacent to current carrying lines or can be substantially of identical structure to trilayered MTJ cells. Once the magnetically labeled molecules have been guided into the appropriate channels, their optical labels can be detected by a process of optical excitation and de-excitation. The molecules are thereby identified and counted.

First claim

What is claimed is:

1. A device for guided transport of magnetically labeled entities comprising:
a substantially planar confining region, said region having a bottom surface and confining sides for confining a liquid solution containing mobile magnetically labeled entities, said confining region including at least one sample pool region and at least one concentrating region and wherein said at least one concentrating region guides said entities into at least one transport channel; and
an array of discrete, patterned, layered thin film magnetic structures for transporting said magnetically labeled mobile entities within said confining region, wherein each said structure comprises three parallel layers, two of said layers having magnetic moments of substantially equal magnitude, being separated by a non-magnetic layer, wherein the magnetic moment of one layer is pinned in direction but wherein the magnetic moment of the other layer is free to move and can be changed in direction relative to that of the pinned layer from parallel to antiparallel by application of an electric current in a conducting line adjacent to said structure;
wherein said structures are formed beneath said bottom surface, each said structure having a length and a width and a horizontal cross-sectional shape having at least four edges and wherein at least two of said edges are parallel to each other and transverse to said transport channel and whose separation defines said width and wherein facing adjacent edges of immediately neighboring said structures are substantially parallel to each other and there is a uniform spacing therebetween; and
a source of a variable external magnetic field that is directed substantially perpendicularly to the plane of said confining region wherein said magnetic field impinges upon said magnetic labels; and

whereby
trapping or releasing energy states of said magnetic labels are formed when said magnetic labels are between separated edges of adjacent layered structures in accord with relative directions of their magnetic moments combined with the effects of said external magnetic field on said magnetic labels;

whereby
spatially sequential and temporally synchronized directional changes of said free layer magnetic moments produced by corresponding variations of said electric current flowing adjacent to each said structure within said array, when acting together with a temporally synchronized application of said external magnetic field produces a corresponding synchronous progression of said magnetic labels towards low energy states that transports said magnetically labeled mobile entities from said at least one holding pool region, through said at least one concentration region and, thereafter, on a single entity at a time basis, into said at least one transport channel.

2. The device of claim 1 wherein said entities also include optically excitable labels and wherein said device includes an optical detecting unit capable of exciting said labels with incident radiation and detecting the radiation emitted therefrom as said entities move past said optical detecting unit, in a one-at-a-time fashion implemented by said synchronous progression of trapping and release states, while guided and transported through said at least one transport channel.

3. The device of claim 2 , wherein said optical detection of said labeled entity is by an optical signal generated by a luminescent or fluorescent dye attached to said entity, whereby a counting of the population of said entities can be performed by excitation and detection optics situated adjacent to said transport channel and focused on an area thereof preferably wherein said one-at-a-time motion occurs.

4. The device of claim 1 wherein said magnetic labels are superparamagnetic particles.

5. The device of claim 4 wherein a magnetization is induced in said particles by magnetic fields produced at an edge of said patterned magnetic structure or between parallel facing adjacent edges of adjacent patterned magnetic structures when a net amount of magnetic charge appears at said edge or between said edges.

6. The device of claim 5 wherein a local minimum of magnetostatic energy associated with the combined fields of said particles and said patterned magnetic structures produces a trapping state for said particles.

7. The device of claim 1 wherein said externally applied magnetic field induces a magnetization in said particle to predispose said particle to move towards a trapping state.

8. The device of claim 1 , wherein each said patterned magnetic thin film structure comprises:
a first magnetic layer having parallel lateral edges directed in a first direction and having a magnetic moment that can be switched between two orientations along a second direction that is substantially perpendicular to said first direction;
a second magnetic layer formed identically to and coextensive with said first layer, said second layer having a magnetic moment that is pinned in one orientation along said second direction,
a non-magnetic layer formed between and separating said first and second magnetic layers; wherein said first and second magnetic layers and said non-magnetic layer share a common horizontal cross-sectional shape that is rhombic, trapezoidal, rectangular or square; and
a current carrying layer formed over said first layer or under said second layer and extending in said first direction.

9. The device of claim 8 , wherein a current flowing in the layer plane of said current carrying layer in said first direction can produce a magnetic field in said second direction to switch a magnetic moment direction of said first layer.

10. The device of claim 9 , wherein when said first layer magnetic moment is switched by the current field to be in the same direction as the magnetic moment of said second magnetic layer, said two magnetic layers produce a magnetic field at said lateral edges, which is of sufficient strength to attract said magnetic labels and trap them on said edges.

11. The device of claim 9 , wherein when said first layer magnetic moment is switched by the current field to be in the opposite direction as the magnetic moment of said second magnetic layer the magnetic fields from the two magnetic layers cancel each other and produce an effective near zero magnetic field in said magnetic labels, whereby said labels are not trapped and can be released if they were trapped.

12. The device of claim 8 , wherein said second layer magnetic moment is pinned by an adjacent antiferromagnetic layer, or by a synthetic antiferromagnetic structure or by an internal crystalline anisotropy.

13. The device of claim 1 , wherein each said patterned magnetic thin film structure comprises:
a first magnetic layer having parallel lateral edges directed in a first direction and having a magnetic moment that can be switched between two orientations along a second direction that is perpendicular to said first direction;
a second magnetic layer formed identically to and coextensive with said first layer, said second layer having a magnetic moment that is pinned in one orientation along said second direction,
a non-magnetic layer formed between and separating said first and second magnetic layers and serving as a current carrying layer; wherein
said three layers have a common horizontal cross-sectional shape.

14. The device of claim 13 wherein said common cross-sectional shape is rhombic, trapezoidal or rectangular.

15. The device of claim 1 wherein each of said patterned, layered thin film magnetic structures is formed of two layers, wherein each of said two layers has a width and

Assignees

• Zhou Yuchen
• Guo Yimin
• Headway Tech Inc

Inventors

• Zhou Yuchen
• Guo Yimin

Classifications

• B03C2201/26

  for use in medical or biological applications · CPC title

• B03C1/033 Primary

  characterised by the magnetic circuit · CPC title

• B03C1/288

  disposed at the outer circumference of a recipient · CPC title

• B03C1/034

  characterised by the matrix elements · CPC title

• B03C2201/18

  Magnetic separation whereby the particles are suspended in a liquid · CPC title