# US 11,112,468 B2 · Magnetoresistive sensor array for molecule detection and related detection schemes

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- Number: US 11,112,468 B2
- Document ID: US11112468B2
- Status: Granted
- Kind: B2
- Application number: 16/659,383
- Filed: 2019-10-21
- Published: 2020-10-15
- Granted: 2021-09-07
- Earliest claimed: 2019-04-12
- Assignees: Western Digital Technologies, Inc.
- Applicants: Western Digital Technologies, Inc.
- Inventors: Patrick Braganca; Daniel Bedau
- Web page: https://patentgrep.com/patent/US11112468B2

## CPC

- G01R 33/093: {using multilayer structures, e.g. giant magnetoresistance sensors (thin magnetic films H01F10/00)}
- C12Q 1/6869: Methods for sequencing
- C12Q 1/6874: involving nucleic acid arrays, e.g. sequencing by hybridisation
- G01N 27/745: {for detecting magnetic beads used in biochemical assays (concerning the assays G01N33/54326; sensors therefor G01R33/1269; automatic analysers therefor G01N35/0098)}
- G01R 33/0029: {Treating the measured signals, e.g. removing offset or noise}
- G01R 33/0041: {using feed-back or modulation techniques}
- G01R 33/0094: {Sensor arrays}
- G01R 33/091: {Constructional adaptation of the sensor to specific applications}
- G01R 33/098: {comprising tunnel junctions, e.g. tunnel magnetoresistance sensors}
- G01R 33/1269: {of molecules labeled with magnetic beads (magnetic particles for bio assay G01N33/54326)}
- G01R 33/1276: {of magnetic particles, e.g. imaging of magnetic nanoparticles (G01R33/1269 takes precedence)}
- G01R 33/1284: {Spin resolved measurements; Influencing spins during measurements, e.g. in spintronics devices}
- G11B 5/02: Recording, reproducing, or erasing methods; Read, write or erase circuits therefor
- G11B 5/3903: {using magnetic thin film layers or their effects, the films being part of integrated structures}
- C12Q 2563/107: fluorescence
- G11B 5/3909: {Arrangements using a magnetic tunnel junction}
- G01R: MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES (indicating correct tuning of resonant circuits H03J3/12)
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)
- G11B: INFORMATION STORAGE BASED ON RELATIVE MOVEMENT BETWEEN RECORD CARRIER AND TRANSDUCER (recording measured values in a way that does not require playback through a transducer G01D9/00; recording or playback apparatus using mechanically marked tape, e.g. punched paper tape, or using unit records, e.g. punched or magnetically marked cards G06K; transferring data from one type of record carrier to another G06K1/18; circuits for coupling output of reproducer to radio receiver H04B1/20; gramophone pick-ups or like acoustic electromechanical transducers or circuits therefor H04R)

## Abstract

A sensing device comprises a plurality of magnetoresistive (MR) sensors, at least one fluidic channel, and detection circuitry coupled to the MR sensors. Each MR sensor is configured to detect the presence of molecules (e.g., biologic molecules) labeled by magnetic nanoparticles (MNPs). The sensors are encapsulated by an insulating material that protects the sensors from the contents of the at least one fluidic channel. The insulating material has a surface within the fluidic channel that provides sites for binding the molecules to be detected. The detection circuitry is configured to detect (a) a characteristic of magnetic noise of each MR sensor, the characteristic being influenced by a presence or absence of one or more MNPs at each site, or (b) a change in resistance, current, and/or voltage drop of each MR sensor, wherein the change is influenced by the presence or absence of one or more MNPs at each site.

## Claims

### Claim 1

A sensing device, comprising:
at least one fluidic channel configured to receive a plurality of molecules to be detected, wherein at least some of the plurality of molecules to be detected are coupled to respective magnetic nanoparticles (MNPs);
a plurality of magnetoresistive (MR) sensors;
an insulating material encapsulating the plurality of MR sensors and for providing a barrier between the plurality of MR sensors and contents of the at least one fluidic channel; and
detection circuitry coupled to each of the plurality of MR sensors,
wherein:
a surface of the insulating material within the fluidic channel provides a plurality of sites for binding the plurality of molecules to be detected, the plurality of sites being located among the plurality of MR sensors, and
the detection circuitry is configured to detect a characteristic of a magnetic noise of each of the plurality of MR sensors, wherein the characteristic of the magnetic noise is influenced by a presence or absence of one or more MNPs at each of the plurality of sites.

### Claim 2 (depends on 1)

The sensing device of claim 1, wherein the characteristic is an amplitude of the magnetic noise at a particular frequency or within a particular frequency band.

### Claim 3 (depends on 2)

The sensing device of claim 2, wherein the detection circuitry comprises:
a bias element coupled to at least one of the plurality of MR sensors and configured to generate a bias across the at least one of the plurality of MR sensors;
a first low pass filter and amplifier combination coupled to the at least one of the plurality of MR sensors to filter and amplify a signal from the at least one of the plurality of MR sensors;
a reference oscillator configured to generate a reference signal having a particular frequency chosen to maximize a change in the signal at the particular frequency when at least one of the one or more MNPs labeling a particular molecule type is detected by the at least one of the plurality of MR sensors at one or more of the plurality of sites;
a mixer coupled to the reference oscillator and an output of the first low pass filter and amplifier combination, wherein the mixer is configured to mix an output signal from the first low pass filter and amplifier combination with the reference signal;
a second low pass filter and amplifier combination coupled to the mixer; and
an envelope detector configured to receive an output signal from the second low pass filter and amplifier combination and provide a signal for detection, wherein a voltage of the signal for detection is proportional to the amplitude of the magnetic noise.

### Claim 4 (depends on 1)

The sensing device of claim 1, wherein the characteristic is a fluctuation of the magnetic noise.

### Claim 5 (depends on 4)

The sensing device of claim 4, wherein the detection circuitry comprises:
a bias element coupled to at least one of the plurality of MR sensors and configured to generate a bias across the at least one of the plurality of MR sensors;
an amplifier coupled to the at least one of the plurality of MR sensors to filter and amplify a signal from the at least one of the plurality of MR sensors;
a filter coupled to the amplifier; and
an envelope detector configured to receive an output signal from the filter and provide a signal for detection, wherein a voltage of the signal for detection is proportional to the fluctuation of the magnetic noise.

### Claim 6 (depends on 1)

The sensing device of claim 1, wherein the characteristic is a phase of the magnetic noise.

### Claim 7 (depends on 6)

The sensing device of claim 6, wherein the detection circuitry comprises a phase locked loop configured to provide an error signal output that corresponds to the phase of the magnetic noise.

### Claim 8 (depends on 1)

The sensing device of claim 1, further comprising:
a plurality of lines coupled to the plurality of MR sensors; and
a plurality of selector elements, each of the plurality of selector elements coupled to at least one of the plurality of lines and to a respective one of the plurality of MR sensors.

### Claim 9 (depends on 8)

The sensing device of claim 8, wherein the plurality of selector elements comprises a transistor.

### Claim 10 (depends on 8)

The sensing device of claim 8, wherein the plurality of selector elements comprises an in-stack selector element.

### Claim 11 (depends on 1)

The sensing device of claim 1, wherein the sensing device is a sequencing device, and wherein the molecules are biologic molecules.

### Claim 12 (depends on 11)

The sensing device of claim 11, wherein the biologic molecules are nucleic acid molecules.

### Claim 13 (depends on 1)

The sensing device of claim 1, wherein at least one of the MR sensors comprises a pinned layer, a free layer, and a spacer layer disposed between the pinned layer and the free layer, and wherein, absent an applied magnetic field and absent the presence of one or more MNPs, an orientation of a magnetic moment of the free layer is approximately 90° from an orientation of a magnetic moment of the pinned layer.

### Claim 14 (depends on 1)

The sensing device of claim 1, wherein:
a first subset of the plurality of MR sensors is arranged in a first row;
a second subset of the plurality of MR sensors is arranged in a second row, the second row being parallel to the first row; and
the at least one fluidic channel is disposed between the first and second rows.

### Claim 15 (depends on 1)

The sensing device of claim 1, further comprising a selector element.

### Claim 16 (depends on 15)

The sensing device of claim 15, wherein the selector element comprises a transistor.

### Claim 17 (depends on 15)

The sensing device of claim 15, wherein the selector element is an in-stack selector element.

### Claim 18 (depends on 1)

The sensing device of claim 1, further comprising a magnetic component configured to apply a magnetic field across the sensing device.

### Claim 19 (depends on 18)

The sensing device of claim 18, wherein the magnetic component comprises one or more of an electromagnet, a distributed coil, a solenoid, a permanent magnet, or a super-conducting magnet.

### Claim 20 (depends on 1)

A method of using the sensing device of claim 1, comprising:
applying a magnetic field across the sensing device; and
the detection circuitry detecting the characteristic of the magnetic noise of each of the plurality of MR sensors.

### Claim 21 (depends on 20)

The method of claim 20, wherein, in a vicinity of each of the plurality of MR sensors, the applied magnetic field is (a) in a substantially same direction as a field emanating from the one or more MNPs, or (b) in a substantially opposite direction from the field emanating from the one or more MNPs.

### Claim 22 (depends on 1)

A method of fabricating the sensing device of claim 1, wherein at least one of the MR sensors comprises a pinned layer, a free layer, and a spacer layer disposed between the pinned layer and the free layer, and wherein an orientation of a magnetic moment of the free layer is approximately 90° from an orientation of a magnetic moment of the pinned layer, and wherein the method comprises at least one of:
applying a hard bias field;
patterning the at least one of the MR sensors into a rectangle or ellipse;
etching the free and pinned layers along an axis to induce texturing; or
using perpendicular magnetic anisotropy to pull the free layer out of plane while keeping the pinned layer in the plane of the at least one of the MR sensors.

### Claim 23

A sensing device, comprising:
at least one fluidic channel configured to receive a plurality of molecules to be detected, wherein at least some of the plurality of molecules to be detected are coupled to respective magnetic nanoparticles (MNPs);
a plurality of magnetoresistive (MR) sensors;
an insulating material encapsulating the plurality of MR sensors and for providing a barrier between the plurality of MR sensors and a contents of the at least one fluidic channel; and
detection circuitry coupled to each of the plurality of MR sensors,
wherein:
a surface of the insulating material within the fluidic channel provides a plurality of sites for binding the plurality of molecules to be detected, the plurality of sites being located among the plurality of MR sensors, and
the detection circuitry is configured to detect one or more of a change in resistance, current, or voltage drop across each of the plurality of MR sensors, wherein the change in resistance, current, or voltage drop is influenced by the presence or absence of one or more MNPs at each of the plurality of sites.

### Claim 24 (depends on 23)

The sensing device of claim 23, wherein the detection circuitry is further configured to report the change in resistance, current, or voltage drop as a binary output that indicates the presence or absence of a particular MNP labeling a particular molecule type at each of the plurality of sites.

### Claim 25 (depends on 23)

The sensing device of claim 23, wherein the detection circuitry is further configured to report the change in resistance, current, or voltage drop at each of the plurality of sites as a quantized output having one of a plurality of levels, at least some of the levels being used to differentiate MNPs having different saturation magnetizations, with each saturation magnetization corresponding to a particular MNP labeling a particular molecule type.

### Claim 26 (depends on 23)

The sensing device of claim 23, further comprising:
a plurality of lines coupled to the plurality of MR sensors; and
a plurality of selector elements, each of the plurality of selector elements coupled to at least one of the plurality of lines and to a respective one of the plurality of MR sensors.

### Claim 27 (depends on 26)

The sensing device of claim 26, wherein the plurality of selector elements includes a transistor.

### Claim 28 (depends on 26)

The sensing device of claim 26, wherein the plurality of selector elements comprises an in-stack selector element.

### Claim 29 (depends on 23)

The sensing device of claim 23, wherein the sensing device is a sequencing device, and wherein the molecules are biologic molecules.

### Claim 30 (depends on 29)

The sensing device of claim 29, wherein the biologic molecules are nucleic acid molecules.

### Claim 31 (depends on 23)

The sensing device of claim 23, wherein each of the MR sensors comprises a pinned layer, a free layer, and a spacer layer disposed between the pinned layer and the free layer, and wherein, absent an applied magnetic field and absent the presence of one or more MNPs, an orientation of a magnetic moment of the free layer is approximately 90° from an orientation of a magnetic moment of the pinned layer.

### Claim 32 (depends on 23)

The sensing device of claim 23, wherein:
a first subset of the plurality of MR sensors is arranged in a first row;
a second subset of the plurality of MR sensors is arranged in a second row, the second row being parallel to the first row; and
the at least one fluidic channel is disposed between the first and second rows.

### Claim 33 (depends on 23)

The sensing device of claim 23, further comprising a selector element.

### Claim 34 (depends on 33)

The sensing device of claim 33, wherein the selector element comprises a transistor.

### Claim 35 (depends on 33)

The sensing device of claim 33, wherein the selector element is an in-stack selector element.

### Claim 36 (depends on 23)

A method of fabricating the sensing device of claim 23, wherein at least one of the MR sensors comprises a pinned layer, a free layer, and a spacer layer disposed between the pinned layer and the free layer, and wherein an orientation of a magnetic moment of the free layer is approximately 90° from an orientation of a magnetic moment of the pinned layer, and wherein the method comprises at least one of:
applying a hard bias field;
patterning the at least one of the MR sensors into a rectangle or ellipse;
etching the free and pinned layers along an axis to induce texturing; or
using perpendicular magnetic anisotropy to pull the free layer out of plane while keeping the pinned layer in the plane of the at least one of the MR sensors.