U.S. patent application number 14/958753 was filed with the patent office on 2016-03-31 for identification of molecules based on frequency responses using electromagnetic write-heads and magneto-resistive sensors.
The applicant listed for this patent is International Business Machines Corporation. Invention is credited to Allen K. Bates, Anna W. Topol, Daniel J. Winarski.
Application Number | 20160091461 14/958753 |
Document ID | / |
Family ID | 47262306 |
Filed Date | 2016-03-31 |
United States Patent
Application |
20160091461 |
Kind Code |
A1 |
Bates; Allen K. ; et
al. |
March 31, 2016 |
IDENTIFICATION OF MOLECULES BASED ON FREQUENCY RESPONSES USING
ELECTROMAGNETIC WRITE-HEADS AND MAGNETO-RESISTIVE SENSORS
Abstract
The invention relates to the identification of molecules using
electromagnetic write-heads and magneto-resistive sensors. In one
embodiment, an electromagnetic write-head magnetically excites a
molecule with an alternating magnetic field. A magneto-resistive
sensor measures the resonant response of the magnetically excited
molecule. A processor compares the resonant response to a table of
known responses of different molecules to identify the chemical
composition of the molecule based in whole or in part on the
comparison.
Inventors: |
Bates; Allen K.; (Tucson,
AZ) ; Topol; Anna W.; (Clifton Park, NY) ;
Winarski; Daniel J.; (Tucson, AZ) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
International Business Machines Corporation |
Armonk |
NY |
US |
|
|
Family ID: |
47262306 |
Appl. No.: |
14/958753 |
Filed: |
December 3, 2015 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
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13151258 |
Jun 1, 2011 |
9229071 |
|
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14958753 |
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Current U.S.
Class: |
324/252 |
Current CPC
Class: |
G01N 27/72 20130101;
G01R 33/091 20130101; G01R 33/1269 20130101; G01R 33/093
20130101 |
International
Class: |
G01N 27/72 20060101
G01N027/72 |
Claims
1. An apparatus, comprising: an electromagnetic write-head
configured to magnetically excite a molecule to be identified with
an alternating magnetic field, wherein the molecule to be
identified is disposed on a biosample substrate configured for use
with the apparatus; a magneto-resistive sensor configured to
measure a resonant response of the magnetically excited molecule to
be identified; and a processor coupled to the magneto-resistive
sensor, the processor being configured to: compare the resonant
response to a table of known resonant responses; and identify a
chemical composition of the molecule to be identified based on the
comparison.
2. The apparatus of claim 1, comprising a magnetic shield
configured to prevent cross-talk between the electromagnetic
write-head and the magneto-resistive sensor while the
electromagnetic write-head magnetically excites the molecule to be
identified.
3. The apparatus of claim 2, comprising a position error servo
(PES) read head configured to align the electromagnetic write-head
and the magneto-resistive sensor with a biosample track in the
biosample substrate.
4. The apparatus of claim 3, wherein the PES read head comprises
one or more of a GMR sensor, a TMR sensor, and an AMR sensor.
5. The apparatus of claim 1, comprising a protective layer
configured to electrically insulate the electromagnetic write-head
from the molecule to be identified.
6. The apparatus of claim 5, the protective layer comprising
diamond-like carbon (DLC).
7. The apparatus of claim 1, comprising an outer layer configured
to protect the electromagnetic write-head from corrosion.
8. The apparatus of claim 7, the outer layer comprising one or more
of gold and platinum.
9. The apparatus of claim 1, the electromagnetic write-head
comprising a thin-film write-head.
10. The apparatus of claim 1, comprising a protective layer
configured to electrically insulate the magneto-resistive sensor
from the molecule to be identified.
11. The apparatus of claim 10, the protective layer comprising
diamond-like carbon (DLC).
12. The apparatus of claim 1, comprising an outer layer configured
to protect the magneto-resistive sensor from corrosion.
13. The apparatus of claim 12, the outer layer comprising one or
more of gold and platinum.
14. The apparatus of claim 1, the processor being configured to
identify the chemical composition in response to determining, based
on the comparison, a correlation between the measured resonant
response of the magnetically excited molecule to be identified and
an ideal resonant response for the chemical composition exceeds a
predetermined correlation threshold.
15. The apparatus of claim 1, the resonant response table
comprising a matched filter.
16. The apparatus of claim 1, comprising a magnet configured to
facilitate the measurement of the resonant response by exposing the
molecule to be identified to a DC magnetic field while the molecule
to be identified is being magnetically excited by the alternating
magnetic field.
17. The apparatus of claim 1, the biosample substrate comprising a
plurality of biosample tracks.
18. The apparatus of claim 1, comprising: a plurality of the
electromagnetic write-heads; and a plurality of the
magneto-resistive sensors; and wherein the electromagnetic
write-heads and the magneto-resistive sensors are arranged in a
plurality of head/sensor pairs.
19. The apparatus of claim 1, comprising an amplifier configured to
amplify the resonant response of the magnetically excited molecule
to be identified.
20. The apparatus of claim 1, wherein the biosample substrate
comprises one or more of a Peltier substrate and a magnetic tape
medium.
Description
BACKGROUND
[0001] The invention relates to analytical devices and processes,
and more particularly, to devices and processes that incorporate
electromagnetic write-heads and magneto-resistive read-sensors to
identify the chemical composition of molecules based on the
frequency responses of magnetically excited molecules.
[0002] Microchip sensors are incorporated into bio-assay devices
and systems to detect the presence of viruses, cancer proteins, and
other biological substances of interest. The microchip sensors may
be in the form of silicon chip arrays and contain thousands of
sensors, each coated with a different antibody that would latch on
a particular virus or protein, and thus indicating the presence of
target viruses or proteins and their concentration in a biological
sample.
[0003] It is desirable to exploit the use of magnetic signaling
technology to automate the identification of molecules, such as
viruses and cancer proteins, and to further apply this technology
to the detection of any biological matter.
BRIEF SUMMARY
[0004] Exemplary embodiments of the invention relate to analytical
devices and processes. More particularly, the embodiments provide
an apparatus, method, and computer program product that use
electromagnetic write-heads and magneto-resistive read-sensors to
identify the chemical composition of molecules based on the
frequency responses of magnetically excited molecules.
[0005] In an exemplary embodiment of the invention, an apparatus
for identifying a molecule is disclosed. The apparatus includes an
electromagnetic write-head configured to magnetically excite a
molecule to be identified with an alternating magnetic field, a
magneto-resistive sensor for measuring the resonant response of the
magnetically excited molecule, and a processor for comparing the
resonant response to a table of known responses to identify the
chemical composition of the molecule. The molecule to be identified
is disposed on a biosample substrate configured for use with the
apparatus.
[0006] In further embodiments, methods and computer program
products for identifying a molecule are disclosed.
[0007] For a fuller understanding of the invention, reference is
made to the following detailed description taken in conjunction
with the accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
[0008] FIG. 1 illustrates a top view of an exemplary substrate that
includes biosample tracks for carrying biosample molecules that may
be scanned and identified by the embodiments of the invention.
[0009] FIG. 2 is a block diagram of an exemplary Z-pattern
servo-alignment mark for aligning an electromagnetic read-write
head with a biosample track, in accordance with an embodiment of
the invention.
[0010] FIG. 3 is a block diagram of a side view of an exemplary
biosample track relative to an electromagnetic read-write head for
analyzing and identifying molecules in a biosample, in accordance
with an embodiment of the invention.
[0011] FIG. 4A illustrates a block diagram of a system for
identifying a molecule using an electromagnetic read-write head, in
accordance with an embodiment of the invention.
[0012] FIG. 4B illustrates an example of a glucose molecule being
encapsulated in a carbon nanotube, in accordance with an embodiment
of the invention.
[0013] FIG. 5 is a block diagram of an exemplary circuit for
controlling the X-axis and Y-axis motion of the read-write
head-module of an analytical device, in accordance with an
embodiment of the invention.
[0014] FIG. 6 is a block diagram of an exemplary write and read
circuit for use with an analytical device, in accordance with an
embodiment of the invention.
[0015] FIG. 7 is a flowchart illustrating an exemplary process for
identifying a molecule using an electromagnetic read-write head, in
accordance with an embodiment of the invention.
DETAILED DESCRIPTION
[0016] Embodiments of the invention relate to methods and systems
for identifying molecules in biosamples using electromagnetic
thin-film write-heads and magneto-resistance read-sensors. The
invention is described in exemplary embodiments with reference to
the Figures, in which like numbers represent the same or similar
elements. It will be appreciated by those skilled in the art that
variations may be accomplished in view of these teachings without
deviating from the spirit or scope of the invention.
[0017] Referring to FIG. 1, there is illustrated a top view of an
example substrate 101, which may comprise a Peltier.TM.
hard-substrate, a glass substrate, a polyethylene terephthalate
(PET, which is commonly known by the trade name of Mylar.TM.)
flexible-substrate, or other materials having similar properties.
In an exemplary embodiment of the invention, head-module 105 scans
across stationary substrate 101 from left-to-right, along the
+Y-axis, individually sampling one or simultaneously sampling a
plurality of biosample tracks 102. Alternatively, substrate 101 may
be swept across stationary head-module 105 from right-to-left,
along the -Y-axis. If substrate 101 is of a flexible polyethylene
terephthalate material, then in one embodiment, this right-to-left
motion may be performed as data read-write operations in a magnetic
tape drive. As an alternate embodiment of the invention,
head-module 105 comprises a helical-scan rotary head-module, and
the Y-axis of the biosample tracks 102 is at an angle to the
substrate.
[0018] FIG. 1 shows electromagnetic write-heads 107 and
magneto-resistive read-sensors 106 arranged in pairs in head-module
105. In one embodiment, write-heads 107 and read-sensors 106 are on
the same head-module 105. In an alternate embodiment, write-heads
107 and read-sensors 106 may be independently adjustable. In yet
another embodiment, a write-head 107 and a read-sensor 106 in a
pair may be orthogonal to one another so that the magnetic
excitation signal of write-head 107 is less dominant to read-sensor
106. The electromagnetic write-heads 107 first write to biosample
tracks 102, and then the adjacent magneto-resistive read-sensors
107 immediately read from biosample tracks 102, which is referred
to as a read-after-write operation. The magnetic excitation of a
molecule by a write-head 107 may be done with a "spike" or impulse
signal. In an alternate embodiment, the write head 107 magnetically
excites the molecule with a swept sine or random noise
magnetic-excitation and the read head simultaneously reads the
resonant response of the molecule.
[0019] In an exemplary embodiment of the invention, substrate 101
comprises eight biosample tracks 102 corresponding to eight bits in
a byte, and hence to eight electromagnetic write-head 107 and
magnetoresistive read-sensor 106 pairs in a typical head-module 105
used in magnetic tape drive products. However, as alternatives, any
number of biosample tracks 102 may be used. The number of
electromagnetic write-head 107 and magneto-resistive read-sensor
106 pairs in head-module 105 may be any number ranging from a
minimum of one to the number of electromagnetic write-head and
magneto-resistive read-sensor pairs in the head-modules of the tape
drives. For example, there are sixteen such electromagnetic
write-head and magneto-resistive read-sensor pairs in a head module
of an IBM 3480.TM. tape drive. Typically, the number of biosample
tracks 102 is an integral multiple of the number of write-head 107
and read-sensor 106 pairs. In an alternate embodiment, a single
device may perform the functions of both the write-head 107 and
read-sensor 106.
[0020] Write-heads 107 may comprise miniature electromagnets, with
a coil sandwiched between to poles, such as taught without
limitation by U.S. Pat. No. 5,452,164, entitled "Thin Film Magnetic
Write-head," which is hereby incorporated by reference in its
entirety. Write-heads 107 may comprise other structures with
similar functionality.
[0021] Read-sensors 106 may be anisotropic magneto-resistive (AMR),
giant magneto-resistive (GMR), or tunnel magneto-resistive (TMR)
read-sensors, or other devices having similar functionality. AMR
read-sensors are taught without limitation by U.S. Pat. No.
5,005,096, entitled "Magnetoresistive Read Transducer Having Hard
Magnetic Shunt Bias," which is hereby incorporated by reference in
its entirety. AMR read-sensors may comprise other structures having
similar functionality. GMR read-sensors, which are also known as
spin-valve read-sensors, are taught without limitation by U.S. Pat.
No. 5,206,590, entitled "Magnetoresistive Sensor Based On The Spin
Valve Effect," which is hereby incorporated by reference in its
entirety. GMR read-sensors may comprise other structures having
similar functionality.
[0022] The GMR read-sensors typically have an internal antiparallel
pinned layer for increased sensitivity, as taught without
limitation by U.S. Pat. No. 5,465,185, entitled "Magnetoresistive
Spin Valve Sensor With Improved Pinned Ferromagnetic Layer And
Magnetic Recording System Using The Sensor," which is hereby
incorporated by reference in its entirety. A recent form of
read-sensor, TMR, uses a tunnel barrier layer to augment the GMR
internal structure and to provide increased sensitivity, as taught
without limitation by U.S. Pat. No. 5,764,567, entitled "Magnetic
Tunnel Junction Device With Nonferromagnetic Interface Layer For
Improved Magnetic Field Response," which is hereby incorporated by
reference in its entirety. TMR read-sensors may comprise other
structures having similar functionality.
[0023] In the exemplary embodiment illustrated in FIG. 1,
write-head 107 is longer along the X-axis direction than
read-sensor 106. The active sensing portion of read-sensor 106 is
smaller than write-head 107, along the X-axis, as write-head 107 is
used to magnetically excite molecule 302 as described with
reference to FIG. 3, for identifying the molecule 302 by
read-sensor 106. If read-sensor 106 were too large in the X-axis
direction, it could potentially encounter non-magnetically excited
molecules 302 and thus register an undesired false identification
of molecule 302, as described with reference to FIG. 3.
[0024] Head-module 105 may be maintained in linear alignment with
biosample tracks 102 along the X-axis by position-error-servo (PES)
read-head 108, which reads magnetically encoded servo-alignment
marks 104 from servo track 103 on substrate 101. PES read-head 108
may be, for example, an AMR, GMR, or TMR read-sensor. Magnetically
encoded servo alignment marks 104 are encoded by the manufacturer
of substrate 101 on either a piece of magnetic tape adhered to
substrate 101 or encoded on a magnetic recording layer directly
deposited on substrate 101.
[0025] In the example illustrated in FIG. 1, particular
servo-alignment marks 104 shown in servo track 103 are Timing Based
Servo (TBS) servo-alignment marks such as those used in IBM's
Linear Tape Open (LTO) tape drive products, e.g., IBM tape drive
models TS1120.TM. and TS1210.TM.. TBS servo-alignment marks are
taught without limitation by U.S. Pat. No. 6,320,719, entitled
"Timing Based Servo System for Magnetic Tape Systems," which is
hereby incorporated by reference in its entirety. Servo-alignment
marks 104 may comprise other structures with similar functionality.
The writing of TBS servo-alignment marks 104 in servo track 103, as
shown in FIG. 1, is taught without limitation by U.S. Pat. No.
6,282,051, entitled "Timing Based Servo System for Magnetic Tape
Systems," which is hereby incorporated by reference in its
entirety. TBS servo-alignment marks 104 may comprise other
structures with similar functionality.
[0026] FIG. 2 illustrates an exemplary embodiment of
servo-alignment marks 104 in the form of magnetically-encoded
Z-pattern 210 that comprises servo-alignment marks in servo track
203. Relative to the Y-axis, the distance between the top and
bottom legs of Z-pattern 210 is constant and equal to the sum of
line segments AB and BC, which is equal to the sum of line segments
A1B1 and B1C1 in path 211. This distance is also equal to the sum
of line segments A2B2 and B2C2 in path 212, and the sum of line
segments A3B3 and B3C3 in path 213. Thus, the velocity of head
module 105 along the Y-axis relative to substrate 101 may be
calculated by dividing the sum of line segments (AB+BC) by the time
to transit Z-pattern 210 by head module 105. This velocity
calculation is not affected by the position of PES read-head 108
along the X-axis, because the top and bottom of Z-pattern 210 are
both parallel to the X-axis.
[0027] The position-error-servo (PES) signal corresponding to the
position of PES read-head 108, and hence write-heads 107 and
read-sensors 106, along the X-axis may be determined by subtracting
the distance AB from the distance BC each time a Z-pattern 210 is
encountered by PES read-head 108. As can be seen in FIG. 2, the PES
signal from PES read-head 108 following path 212 is less than zero
because the distance difference (B2C2-A2B2) is less than zero.
Similarly, the PES signal from PES read-head 108 following path 211
is greater than zero because the difference (B1C1-A1B1) is greater
than zero. Additionally, the value of (BC-AB) varies linearly as
PES read-head 108 moves from left to right along the X-axis. Thus
the PES signal, as calculated by the difference in distance
(BC-AB), provides an X-axis PES signal for head-module 105 and its
pairs of electromagnetic write-heads 107 and magneto-resistive
read-sensors 106. This PES signal is incorporated into servo
control circuit 500 shown in FIG. 5.
[0028] In an exemplary embodiment of the invention, the value of
the line segment difference (BC-AB) is evaluated based on the time
it takes for the PES read head 108 to cross segments AB and BC when
the head-module 105 is moving at a constant velocity during its
Y-axis seek operation. This is the case where the transit time for
the PES read head 108 to cross each Z-pattern 210 is constant. In
the exemplary embodiments of the invention shown in FIGS. 1 and 2,
TBS servo-alignment marks 104 and Z-pattern 210 could be
non-magnetic stripes, either lithographed, silk-screened, or
ink-jet printed, and read with an optical laser.
[0029] In FIG. 2, path 213 is the desired path for PES read-head
108 as electromagnetic write-heads 107 and magneto-resistive
read-sensors 106 are aligned with biosample tracks 102. With path
213, the distance difference (B3C3-A3B3) is equal to zero, i.e.,
line segment B3C3 is equal to line segment A3B3. For path 211, the
distance difference (B1C1-A1B1) is greater than zero, which means
that head-module 105 must be moved in the +X direction by X-axis
actuator 529 of FIG. 5 so that electromagnetic write-heads 107 and
magneto-resistive read-sensors 106 are aligned with biosample
tracks 102. The operation of the X-axis actuator 529 is described
below with reference to FIG. 5. Similarly, for path 212, the
distance difference (B2C2-A2B2) is less than zero, which means that
head-module 105 must be moved in the -X direction by X-axis
actuator 529 so that electromagnetic write-heads 107 and
magneto-resistive read-sensors 106 are aligned with biosample
tracks 102.
[0030] FIG. 3 illustrates a side view of an exemplary biosample
track relative to an electromagnetic read-write head for analyzing
a biosample. A biosample track 301 may be deposited on a substrate
such as a Peltier.TM. substrate or a magnetic tape media as
described in FIGS. 1 and 2. A biosample 302 may be positioned on
the biosample track 301 to be analyzed by an electromagnetic
read-write head 306 in accordance with an embodiment of the
invention. Magnetic shield 305 separates write-head 303 and
read-sensor 304 so that there is no meaningful cross-talk between
write-head 303 and read-sensor 304 while the electromagnetic
read-write head module 306 scans along the biosample track 301. The
scan may be performed by moving head-module read-write head module
306 linearly in the +Y direction relative to biosample track 301,
which could equally be done by moving the substrate carrying the
biosample track 301 linearly in the -Y direction relative to
read-write head-module 306. In an alternate embodiment, write-head
303 and read-sensor 304 may switch positions.
[0031] FIG. 4A illustrates a block diagram of a molecule analysis
system 400 for magnetically exciting molecules 402 in a biosample
302 and identifying the molecules 402 based on the frequency
responses of the magnetically excited molecules, in accordance with
an embodiment of the invention. The molecule analysis system 400
comprises an electromagnetic thin-film write-head 403 for
magnetically exciting the molecules 402 in the biosample 302 while
the electromagnetic thin-film write-head 403 scans biosample track
301.
[0032] In one embodiment, the electromagnetic thin-film write-head
403 may magnetically excite the molecules 402 using a swept-sine
signal. The swept-sine signal is a sine wave with a frequency that
increases over time and may be generated by a signal generator 415.
The electromagnetic thin-film write-head 403 may magnetically
excite the biosample molecules 402 using a range of frequencies in
order to magnetically excite the molecules 402 with an alternating
magnetic field.
[0033] In another embodiment, the electromagnetic thin-film
write-head 403 may magnetically excite the molecules 402 using an
impulse signal having a generally narrow square-wave spike that is
applied once during the measurement of the resonant response.
Alternatively, the electromagnetic thin-film write-head 403 may
magnetically excite the biosample molecules 402 with an alternating
magnetic field that is generated by a random-noise signal. The
random noise signal may be produced by sending a reverse polarity
voltage across a diode.
[0034] In another embodiment, the analytical system 400 may further
expose the molecules 402 to a direct current (DC) magnetic field
while the molecules 402 are being magnetically excited to
facilitate the measurement of the resonant responses from the
magnetically excited molecules 402. A permanent magnet or an
electromagnet may be used to provide such a DC magnetic field. The
DC magnetic field aligns the magnetically excited molecules 402 for
improved signal-to-noise ratio during the alternating magnetic
field excitation.
[0035] The electromagnetic thin-film write-head 403 may be coated
in one or more protective layers such as a diamond carbon layer 411
to act as an electrical insulator between the biosample molecules
402 and the electromagnetic thin-film write-head 403. An outer
layer 412, which may be gold or platinum, covers the diamond carbon
layer 411 and thin-film write-head 403 to protect the thin-film
write-head 403 from corrosion caused by the salinity in the
biosample 302.
[0036] The molecule analysis system 400 further comprises an
electromagnetic read-sensor 404 for sensing the frequency responses
of the magnetically excited molecules 402. Molecules 402 are
comprised of atoms which are bonded together by ionic or covalent
bonds. A mass-spring mechanical system, such as a car and its
springs, will resonate at a natural frequency which is a function
of the square root of the spring rate (in Newtons per meter)
divided by the mass (kilograms), and a multiple spring--multiple
mass system will have multiple resonances. By analogy, bonds
between atoms in molecules provide a spring action and the atoms
themselves possess mass, and thus molecules can have multiple
resonances which are a function of the chemical makeup of the
molecule. It is these resonances that are excited by write-head
403.
[0037] A target molecule 402 may be held in position during its
magnetization by encapsulating it in a carbon nanotube. As an
example, FIG. 4B illustrates an example of a glucose molecule 418
being encapsulated in a carbon nanotube 419. In an alternate
example, a target molecule 402 may be held in place by an antibody,
as taught in the commonly-assigned patent application entitled
"Detection Of Analytes Via Nanoparticle-Labeled Substances With
Electromagnetic Read-Write Heads", Ser. No. 12/888,388, herein
incorporated by reference in its entirety. In another alternate
embodiment, the target molecule 402 is held in position by surface
aligned molecules (SAMs). In yet another alternate embodiment,
target molecule 402 is held in a liquid suspension, such as a
saline suspension. The resonant response of the antibody, SAMs, and
liquid suspension are first gathered without the target molecule
402 so that the resonant response of the target molecule 402 can be
isolated from the surrounding environment.
[0038] The electromagnetic read-sensor 404 may be a giant
magneto-resistance (GMR) sensor, a tunnel magneto-resistance (TMR)
sensor, or an anisotropic magneto-resistance (AMR) sensor.
Similarly to the thin-film write-head 403, the electromagnetic
read-sensor 404 may be coated in one or more protective layers such
as a diamond carbon layer 414 to act as an electrical insulator
between the biosample molecules 402 and the electromagnetic
read-sensor 404. An outer layer 413, which may be gold or platinum,
covers the diamond carbon layer 414 and electromagnetic read-sensor
404 to protect the electromagnetic read-sensor 404 from corrosion
caused by the salinity in the biosample 303.
[0039] The frequency responses of the magnetically excited
biosample molecules 402 that are detected by the electromagnetic
read-sensor 404 are generally small, for example, on the order of
0.1 to 10 microvolts. The molecule analysis system 400 may comprise
an amplifier 416 for amplifying the detected response, which is
then further processed by processor 410 to identify the molecules
402. For example, a solid-state voltage amplifier having a gain
ranging from 10X to 1000X may be used.
[0040] In one embodiment, the processor 410 may compare the
amplified frequency responses, or a range of responses, of the
magnetically excited biosample molecules 402 to a table of known
frequency responses of a group of molecules. For example, the
sucrose molecule, C12H22O11, will have different resonances than
that of polytetrafluoroethylene, C2F4. By identifying the
resonances as a function of their frequency and amplitude, the
molecule analysis system 400 can identify whether a molecule is
sucrose or polytetrafluoroethylene.
[0041] In another embodiment, the processor 410 may calculate Bode
plots of the frequency response of a molecule divided by the
excitation signal to detect tell-tale resonances. The Bode plots
may be calculated by dividing the Fourier transform F(w) of the
amplified frequency response (i.e., the output of the amplifier
416) by the Fourier transform of the signal from the signal
generator 415, in order to normalize the resonant response to the
magnetic-excitation. Alternatively, processor 410 could use power
spectrum or Fourier transforms of the output of the electromagnetic
read-sensor 404 to detect tell-tale resonances. The power spectrum
is the square of the magnitude of the Fourier transform output and
is calculated by taking the product of the Fourier transform times
its complex conjugate. The power spectrum is useful because there
is no phase, only amplitude, and thus resonances are readily
identified.
[0042] The Bode plot is the most useful for detecting the tell-tale
resonances as the output of the electromagnetic read-sensor 404 may
be normalized to the excitation signal to facilitate the
identification of tell-tale resonances. Processor 410 may access an
internal table 420 of known resonant responses for different
biosample molecules 402 and match the measured resonant response
with the internal table 420 to identify the biosample molecules
402. The internal table 420 is stored in a nonvolatile portion of
processor 410 and may include a list of known molecules and their
resonant frequencies, as well as normalized amplitudes of those
resonant frequencies.
[0043] As an example, resonances R1 and R2 may have generally the
same amplitudes but resonance R3 has generally twice the amplitudes
of resonances R1 and R2. The table may include harmonics of these
resonant frequencies, if they exist. For example, resonant
frequency R1 has a first harmonic at frequency 2*R1 and a second
harmonic at frequency 3*R1, but no additional harmonics of
frequency R1 are present. The molecule analysis system 400 may look
up the resonant frequencies, normalized amplitudes, and harmonic
frequencies in identifying the chemical composition of a
molecule.
[0044] In one embodiment, the molecule analysis system 400 may
filter out DC signals from the measured resonant response of the
magnetically excited molecules 402 to improve the signal-to-noise
ratio (SNR) of the response. The removal of the unwanted DC signals
may be accomplished by balancing a resistive Wheatstone bridge in
which one leg of the Wheatstone bridge contains the
magneto-resistive sensor. An example of the use of a Wheatstone
bridge in a molecule resonance sensing circuit is illustrated in
FIG. 6.
[0045] In another embodiment, the molecule analysis system 400 may
further filter out AC noise signals from the measured resonant
response of the magnetically excited molecules 402 to improve the
signal-to-noise ratio (SNR) of the response, using a filter. AC
noises, such as those introduced by lighting and electric power
equipment in a laboratory, may be removed using a band pass filter,
band block filter, high-pass filter, Hamming filter, or Butterworth
filter, which are known to one skilled in the art.
[0046] FIG. 5 shows an exemplary embodiment of a servo control
system 500 for controlling the X-axis and Y-axis motion of
head-module 520. As an example, FIG. 5 shows one biosample track
521, and one pair of write-head 522 and read-sensor 523. Processor
524 receives position-error-servo (PES) signals from PES read-head
525 when PES read-head 525 reads servo-alignment marks 526 in servo
track 527. Based on this PES information, processor 524 sends a
signal to power amplifier 528 to control X-axis actuator 529 which
in turn controls the motion of head module 520 in the X-axis
direction. With X-axis actuator 529 connected to head-module 520
via mechanical connector 530, head-module 520 may be positioned to
center write-head 522 and read-sensor 523 on biosample track 521.
Processor 524 may send signals to power amplifier 531 to control
Y-axis actuator 532 for conducting a scan by head module 520 across
substrate 533. With Y-axis actuator 532 connected to X-axis
actuator 529 via mechanical connector 534, head-module 520 can be
moved along the Y-axis in a controllable manner.
[0047] As an example, when a predetermined number of
servo-alignment marks 526 are read by PES read-head 525, processor
524 stops the Y-axis motion of head-module 520. A servo-system for
control of X-axis actuator 529 and head-module 520 along the X-axis
direction, particular to servo-alignment marks 526 shown in servo
track 527, is taught without limitation by U.S. Pat. No. 5,689,384,
entitled "Timing Based Servo System for Magnetic Tape System,"
which is hereby incorporated by reference in its entirety. The
servo-system may comprise other structures with similar
functionality. As previously described regarding Z-pattern 210, the
velocity of head module 520 relative to substrate 533 along the
Y-axis can be calculated by dividing distance AB+BC by the time it
takes for head module 520 to transit Z-pattern 210. This velocity
measurement can be used by processor 524 to control Y-axis actuator
532 to keep head module 520 at a constant Y-axis velocity Vy
relative to substrate 533. The position along the Y-axis of head
module 520 relative to substrate 533 can be obtained by counting
servo-alignment marks 526 or Z-pattern 210 by PES read head 525 and
processor 524.
[0048] FIG. 6 shows an exemplary embodiment of a write and read
circuitry 600 for writing to a biosample track 621 (i.e., for
magnetically exciting molecules 402) and reading from the biosample
track 621 (i.e., for sensing and identifying the magnetically
excited molecules 402) on substrate 633. Processor 624 may send
signals to power amplifier 646 which provides power to write-head
647 on head module 620 for magnetically exciting molecules 402 with
spike (impulse), swept sine, or random noise wave-forms. Processor
624 may further send signals to power amplifier 645 which powers
Wheatstone bridge 640. Read-sensor 623 is one component in
Wheatstone bridge 640 and thus receives DC current from the
Wheatstone bridge 640. Wheatstone bridge 640 serves the function of
balancing out the zero-magnetism resistance of read-sensor 623 so
that only the change in resistance of read-sensor 623 is passed
onto amplifier 641. Such resistance change is due to the detection
of a resonating 402, which is sent to amplifier 641 and filter 642
before being received by processor 624.
[0049] Filter 642 filters out 60 Hz noise, which is pervasive noise
in an office or laboratory with lighting where processes of the
invention are typically performed. Processor 624 makes the
determination of whether a molecule 402 was detected. The change in
resistance of read-sensor 623 is directly proportional to the
magnetic field provided by a magnetically excited molecule 402. As
a result, processor 624 could register the detection of different
molecules 402 during the sensing of read-sensor 623, depending on
different frequencies received by the read-sensor 623. The
identification of the various molecules 402 simultaneously on the
same biosample track 621 may be facilitated by a lookup table 644
in processor 624, as described in detail with reference to FIG. 7.
In one exemplary embodiment of the invention, the lookup table 644
contains a list of different molecules 402, and their respective
resonance frequencies.
[0050] The resonant response table 644 may include a list of known
molecules and radicals such as H+, OH--, C--H, H--C--H and the
like, and their resonant frequencies, as well as normalized
amplitudes of those resonant frequencies. The resonant response
table 644 may further include harmonics of the resonant
frequencies, if they exist. The resonant frequencies, normalized
amplitudes, and harmonic frequencies assist in the identification
of the chemical composition of the magnetically excited molecules.
A matched filter 643 may be present to provide a correlation
between ideal resonances and the measured resonances, and
resonances are considered to be detected if the correlation exceeds
a user-selectable threshold, such as 80%, where 0% indicates no
correlation and 100% indicates a perfect correlation. PES read head
625, alignment servo marks 626, and servo track 627 are identical
to 525, 526, and 527 of FIG. 5, respectively.
[0051] FIG. 7 is a flowchart illustrating an exemplary process for
identifying a molecule using an electromagnetic read-write head, in
accordance with an embodiment of the invention. The process may be
performed by an excitation-response molecular-identification
system, such as system 400, on a biosample as illustrated in FIGS.
1-3. Such an analytical system 400 may include appropriate
electrical circuits, devices, computer hardware and program
instructions to carry out the illustrated operations. At step 701,
an electromagnetic write-head 403 receives an alternating AC
current and generates an alternating magnetic field which
magnetically excites a target molecule 402. This magnetization
causes an oscillation of the atoms in the molecule 402.
[0052] In one embodiment, the alternating magnetic field generated
by write-head 403 is supplemented by a steady-state,
non-oscillating magnetic field, which may be supplied by a
permanent magnet or an electromagnet supplied with direct DC
current. Such a non-oscillating magnetic field tends to align the
atoms in the molecule to maximize the excitation provided by the
alternating magnetic field, thus increasing the signal-to-noise
ratio (SNR). In an alternate embodiment, the write-head 403
generates the non-oscillating magnetic field that is superimposed
over the alternating magnetic field.
[0053] In one embodiment, the excitation provided by the power
supply feeding write-head 403, and hence the alternating magnetic
field generated by write-head 403 may be a swept-sine signal. The
swept-sine signal is a simple sine wave with a frequency that
changes over time and may be generated by a signal generator 415.
Generally the frequency of the sine wave starts at a low frequency
and increases with time. Alternatively, the frequency of the sine
wave starts at a high frequency and decreases with time.
[0054] In another embodiment, the alternating magnetic field
generated by write-head 403 may be a white noise excitation, which
is the statistical equivalent of random noise. An example of white
noise is the static one hears on an AM radio. The random noise
signal may be generated by sending a reverse polarity voltage
across a diode.
[0055] In a yet another embodiment, the alternating magnetic field
generated by write-head 403 may be an impulse signal, which is a
narrow square wave of a single magnetic polarity. The square wave
is applied only once by the write-head 403 during a sample period,
i.e., during the measurement of the resulting resonant response
from the excited molecule 402. The read-sensor 108 may register the
resonant response only after the generation of the impulse "spike"
wave is completed by write-head 403.
[0056] The goal of the swept sine, white noise, and impulse
excitations is to cause the molecule 402 to resonate, and it is
this resonance which is detected by read-sensor 404. This resonance
may comprise one or more fundamental resonances, and each
fundamental resonance may have harmonic resonances which are
integer multiples of the fundamental resonance. For example, a
fundamental resonance of frequency .omega.1 may have a first
harmonic of frequency 2* .omega.1, a second harmonic of frequency
3* .omega.1, a third harmonic of frequency 4* .omega.1, etc.
[0057] When the atoms in a molecule 402 are magnetically excited,
the molecule 402 generates a resonant response that may be detected
and measured by a magneto-resistive read-sensor 404 in step 702.
The magneto-resistive read-sensor 404 may be, for example, a GMR
sensor, a TMR sensor, or an AMR sensor. The use of these sensors,
which are generally used in data storage tape systems, provides an
advantage when using the tape systems to detect and analyze
antigens. In order to facilitate the measurement of the resonant
response from the magnetically excited molecule 402, the analytical
system 400 may expose the molecule 402 to a DC magnetic field while
the molecule 402 is being magnetically excited by the alternating
magnetic field.
[0058] Magnetic shield 305, as illustrated in FIG. 3, separates
write-head 403 and read-sensor 404 so that there is no harmful
cross-talk between write-head 403 and read-sensor 404 during steps
701 (molecule excitation) and 702 (resonant response measurement).
Read-sensor 404 is typically one leg of a Wheatstone bridge, so
that the nominal (zero-excitation) resistance of the read-sensor
404 may be zeroed-out by balancing the Wheatstone bridge.
Accordingly, the output of the Wheatstone bridge is only the change
in resistance experienced by the read-sensor 404 as it detects the
resonances of the target molecule 402.
[0059] The resonant response from the magnetically excited molecule
402 that the magneto-resistive read-sensor 404 measures is
generally too small for positively identifying the molecule 402.
Thus, an amplifier 641 in the detection circuit 600 may be employed
to amplify the measured response at step 703. Amplifier 641 is
typically a solid state amplifier with predetermined gains of 10X,
100X and 1000X. Such solid state amplifiers may allow user
controlled gain. In addition, the measured resonant response from
the magnetically excited molecule 402 may include a zero-magnetism
resistance of read-sensor 623. This DC signal may be filtered out
from the resonant response, at step 704, by balancing a resistive
Wheatstone bridge in which one leg of the Wheatstone bridge is the
magneto-resistive sensor 404. Such a Wheatstone bridge is
illustrated in FIG. 6. The DC signal filtering assures that only
changes in resistance of read-sensor 623 are passed to the
amplifier 641.
[0060] At step 705, a filter 642 in the detection circuit 600 may
be employed to eliminate AC background noise, such as 60 Hertz
noise emanated by common lighting and electric power equipment in a
laboratory. As examples, the noise filter 642 may be a band pass
filter, band block filter, high-pass filter, Hamming filter, or
Butterworth filter, which are known to one skilled in the art.
[0061] The amplified and filtered resonant response of the
magnetically excited molecule 402 may be further transformed to a
power spectrum at step 706 to facilitate the identification of
fundamental frequencies and harmonic frequencies, as follows.
First, a Fourier transform F(.omega.) is created of the filtered
and amplified output .omega. of the Wheatstone bridge, of which
read-sensor 404 is a part. Fourier transform F(.omega.) is in the
frequency domain, and is the frequency representation of the
time-domain signal from read-sensor 404. Next, the Fourier
transform F(.omega.) is multiplied by its complex conjugate
F*(.omega.) to give the power spectrum .phi.(.omega.) per equations
(1) and (2). Equation (1) is for an analog Fourier transform, one
which is continuous in frequency. Equation (2) is for a digital
Fourier transform, which is expressed, for example, in discrete
increments in frequency.
.PHI. ( .omega. ) = 1 2 .pi. .intg. - .infin. .infin. f ( t ) -
.omega. t t 2 = F ( .omega. ) F * ( .omega. ) 2 .pi. Equation ( 1 )
.PHI. ( .omega. ) = 1 2 .pi. n = - .infin. .infin. f n - .omega. n
2 = F ( .omega. ) F * ( .omega. ) 2 .pi. Equation ( 2 )
##EQU00001##
[0062] The resonances and harmonic frequencies are peaks in the
power spectrum .phi.(.omega.) and may be identified by peak-detect
algorithms, as known in the art, such as used in recording
technology such as for tape drives. The resonances and harmonic
frequencies detected by the read-sensor are compared to a table of
known resonant responses for known chemical radicals, such as H+,
OH--, C--H, H--C--H, etc. From this table, and the aforementioned
resonances and harmonic frequencies, the chemical composition the
target molecule 402 is identified, at step 707. Once the molecule
402 is identified, the analytical system 400 may present the
results of the molecule scan to a physician or clinician at step
708, for example, by informing the physician or clinician of the
presence or absence of target molecules in the biological
sample.
[0063] Referring again to FIG. 1, there may be multiple target
molecules in the biosample tracks 180 that the excitation-response
process described above may identify. If there are more biosample
tracks 180 than write-head 106 and read-sensor 108 pairs in
head-module 104, head-module 104 may scan the biosample tracks 180
in a serpentine pattern. The head-module 104 performs a scan in the
+Y direction, as head-module 104 only provides read-after-write
capability in the +Y direction as illustrated in FIG. 1. Then a
second head-module comprising a mirror image of head-module 104 may
perform a read-after-write operation in the -Y direction. In one
embodiment, during the excitation-response process, the write-head
106 and read-sensor 108 pairs are stationary and physical motion
along the +/-Y direction only occurs in moving from one sample site
to the next. The use of IBM's Timing Based Servo, as read by a
servo read-head on head module 104, may assist in the guiding of
write-head 106 and read-sensor 108 from one target molecule to the
next.
[0064] To facilitate the detection of different target molecules,
calibration of read-sensor 108 may be performed. An exemplary
read-sensor calibration process is described, for example, in the
commonly-assigned patent application entitled "A Circuit For
Detecting Analytes Via Nanoparticle-labeled Substances With
Electromagnetic Read-Write Heads", Ser. No. 12/888,408, herein
incorporated by reference in its entirety. The calibration process
may use of a variety of known molecules positioned in known
locations in biosample tracks 180, where the resonant responses of
these molecules are known. Variants of known molecules are formed
of atoms of carbon isotopes. For example, Carbon-12 is replaced by
Carbon-13 or Carbon-14. This affects the resonances of the known
molecule, causing a shift in the resonant frequencies, because of
the change of mass of the atoms. magnetically excited nanoparticles
of known magnetic intensity may be used in fixed positions along
biosample track 180 to "label" the known molecules used for
calibration purposes. These nanoparticle labels would typically be
of a high coercivity, such as Barium Ferrite, so that the
magnetization of these nanoparticles is not affected by write-head
106 during the excitation-response molecular-identification
process.
[0065] While the exemplary embodiments of the invention have been
illustrated and described in detail, it should be apparent that
modifications and adaptations to those embodiments may occur to one
skilled in the art without departing from the scope of the
invention. Aspects of the present disclosure may be embodied as a
method, system or computer program product, and may take the form
of an entirely hardware embodiment, an entirely software embodiment
(including firmware, resident software, micro-code, etc.) or an
embodiment combining software and hardware aspects that may all
generally be referred to herein as a "circuit," "module" or
"system." Furthermore, aspects of the present disclosure may take
the form of a computer program product embodied in one or more
computer readable medium(s) having computer readable program code
embodied thereon.
[0066] Any combination of one or more computer readable medium(s)
may be utilized. The computer readable medium may be a computer
readable signal medium or a computer readable storage medium. A
computer readable storage medium may be, for example, but not
limited to, an electronic, magnetic, optical, electromagnetic,
infrared, or semiconductor system, apparatus, or device, or any
suitable combination of the foregoing. More specific examples (a
non-exhaustive list) of the computer readable storage medium would
include the following: an electrical connection having one or more
wires, a portable computer diskette, a hard disk, a random access
memory (RAM), a read-only memory (ROM), an erasable programmable
read-only memory (EPROM or Flash memory), an optical fiber, a
portable compact disc read-only memory (CD-ROM), an optical storage
device, a magnetic storage device, or any suitable combination of
the foregoing. In the context of this document, a computer readable
storage medium may be any tangible medium that can contain, or
store a program for use by or in connection with an instruction
execution system, apparatus, or device.
[0067] A computer readable signal medium may include a propagated
data signal with computer readable program code embodied therein,
for example, in baseband or as part of a carrier wave. Such a
propagated signal may take any of a variety of forms, including,
but not limited to, electro-magnetic, optical, or any suitable
combination thereof. A computer readable signal medium may be any
computer readable medium that is not a computer readable storage
medium and that can communicate, propagate, or transport a program
for use by or in connection with an instruction execution system,
apparatus, or device.
[0068] Program code embodied on a computer readable medium may be
transmitted using any appropriate medium, including but not limited
to wireless, wireline, optical fiber cable, RF, etc. or any
suitable combination of the foregoing.
[0069] Computer program code for carrying out operations for
aspects of the present disclosure may be written in any combination
of one or more programming languages, including an object oriented
programming language such as Java, Smalltalk, C++ or the like and
conventional procedural programming languages, such as the "C"
programming language or similar programming languages. The program
code may execute entirely on the user's computer, partly on the
user's computer, as a stand-alone software package, partly on the
user's computer and partly on a remote computer or entirely on the
remote computer or server. In the latter scenario, the remote
computer may be connected to the user's computer through any type
of network, including a local area network (LAN), a wide area
network (WAN), Ethernet, or the connection may be made to an
external computer, for example, through the Internet using an
Internet Service Provider.
[0070] Aspects of the present disclosure are described above with
reference to flowchart illustrations and/or block diagrams of
methods, apparatus (systems) and computer program products
according to embodiments of the disclosure. It will be understood
that each block of the flowchart illustrations and/or block
diagrams, and combinations of blocks in the flowchart illustrations
and/or block diagrams, can be implemented by computer program
instructions. These computer program instructions may be provided
to a processor of a general purpose computer, special purpose
computer, or other programmable data processing apparatus to
produce a machine, such that the instructions, which execute via
the processor of the computer or other programmable data processing
apparatus, create means for implementing the functions/acts
specified in the flowchart and/or block diagram block or
blocks.
[0071] These computer program instructions may also be stored in a
computer readable medium that can direct a computer, other
programmable data processing apparatus, or other devices to
function in a particular manner, such that the instructions stored
in the computer readable medium produce an article of manufacture
including instructions which implement the function/act specified
in the flowchart and/or block diagram block or blocks.
[0072] The computer program instructions may also be loaded onto a
computer, other programmable data processing apparatus, or other
devices to cause a series of operational steps to be performed on
the computer, other programmable apparatus or other devices to
produce a computer implemented process such that the instructions
which execute on the computer or other programmable apparatus
provide processes for implementing the functions/acts specified in
the flowchart and/or block diagram block or blocks.
[0073] The flowchart and block diagrams in the figures described
above illustrate the architecture, functionality, and operation of
possible implementations of systems, methods and computer program
products according to various embodiments of the present
disclosure. In this regard, each block in the flowchart or block
diagrams may represent a module, segment, or portion of code, which
comprises one or more executable instructions for implementing the
specified logical function(s). It should also be noted that, in
some alternative implementations, the functions noted in the block
may occur out of the order noted in the figures. For example, two
blocks shown in succession may, in fact, be executed substantially
concurrently, or the blocks may sometimes be executed in the
reverse order, depending upon the functionality involved. It will
also be noted that each block of the block diagrams and/or
flowchart illustration, and combinations of blocks in the block
diagrams and/or flowchart illustration, can be implemented by
special purpose hardware-based systems that perform the specified
functions or acts, or combinations of special purpose hardware and
computer instructions.
* * * * *