SPIN TORQUE OSCILLATOR (STO) SENSORS USED IN NUCLEIC ACID SEQUENCING ARRAYS AND DETECTION SCHEMES FOR NUCLEIC ACID SEQUENCING
Disclosed herein are methods and apparatuses for sequencing nucleic acids using a detection device, the detection device comprising a plurality of spin torque oscillators (STOs) and at least one fluidic channel. In some embodiments of a method, a nucleotide precursor is labeled with a magnetic nanoparticle (MNP), and the labeled nucleotide precursor is added to the fluidic channel of the detection device. It is determined whether at least one of the plurality of STOs is generating a signal. Based at least in part on the determination of whether the at least one of the plurality of STOs is generating the signal, it is determined whether the labeled nucleotide precursor has been detected.
1 . A method of distinguishing between labeled nucleotide precursors using a detection device and at least two distinct groups of magnetic nanoparticles (MNPs), the detection device comprising a plurality of spin torque oscillators (STOs) and at least one fluidic channel, the method comprising:
labeling a first nucleotide precursor with a first MNP, the first MNP being from a first group of the at least two distinct groups of MNPs, the first group selected to cause a magnetization of each of the plurality of STOs to oscillate at approximately a first frequency;
labeling a second nucleotide precursor with a second MNP, the second MNP being from a second group of the at least two distinct groups of MNPs, the second group selected to cause the magnetization of each of the plurality of STOs to oscillate at approximately a second frequency;
adding the labeled first and second nucleotide precursors to the fluidic channel of the detection device;
detecting a frequency of a signal generated by at least one of the plurality of STOs;
determining whether the frequency of the signal generated by the at least one of the plurality of the STOs matches the first frequency or the second frequency; and
in response to the determining, identifying whether the first nucleotide precursor or the second nucleotide precursor has been detected.
2 . The method of claim 1 , wherein detecting the frequency of the signal generated by the at least one of the plurality of STOs comprises:
collecting samples of the signal generated by the at least one of the plurality of STOs; and
applying a Fourier transform to the samples.
3 . The method of claim 1 , wherein detecting the frequency of the signal generated by the at least one of the plurality of STOs comprises:
collecting samples of the signal generated by the at least one of the plurality of STOs; and
determining frequency content of the samples.
4 . The method of claim 1 , wherein detecting the frequency of the signal generated by the at least one of the plurality of STOs comprises:
multiplying the signal generated by the at least one of the plurality of STOs by a first reference signal of approximately the first frequency; and
multiplying the signal generated by the at least one of the plurality of STOs by a second reference signal of approximately the second frequency,
and wherein determining whether the frequency of the signal generated by the at least one of the plurality of the STOs matches the first frequency or the second frequency comprises:
identifying the frequency of the signal generated by the at least one of the plurality of STOs as the first frequency in response to a result of the multiplying being greater than a first threshold; and
identifying the frequency of the signal generated by the at least one of the plurality of STOs as the second frequency in response to a result of the multiplying being greater than the first threshold or a second threshold.
5 . The method of claim 1 , wherein determining whether the frequency of the signal generated by the at least one of the plurality of the STOs matches the first frequency or the second frequency comprises determining whether the frequency of the signal generated by the at least one of the plurality of STOs is approximately the first frequency or approximately the second frequency.
6 . The method of claim 1 , wherein determining whether the frequency of the signal generated by the at least one of the plurality of the STOs matches the first frequency or the second frequency comprises determining whether the frequency of the signal generated by the at least one of the plurality of STOs is within a first frequency band or within a second frequency band, wherein the first frequency band includes the first frequency, and the second frequency band includes the second frequency.
7 . The method of claim 6 , wherein the first frequency band and the second frequency band are disjoint.
8 . The method of claim 1 , wherein detecting the frequency of the signal generated by the at least one of the plurality of STOs is performed by a super-heterodyne circuit coupled to the at least one of the plurality of STOs.
9 . The method of claim 1 , further comprising:
in response to identifying that the first nucleotide precursor has been detected, recording an identity of the first nucleotide precursor or an identity of a base complementary to the first nucleotide precursor, and/or
in response to identifying that the second nucleotide precursor has been detected, recording an identity of the second nucleotide precursor or an identity of a base complementary to the second nucleotide precursor.
10 . A method of detecting a labeled nucleotide precursor using a detection device, the detection device comprising a plurality of spin torque oscillators (STOs) and at least one fluidic channel, the method comprising:
labeling a nucleotide precursor with a magnetic nanoparticle (MNP);
adding the labeled nucleotide precursor to the fluidic channel of the detection device;
determining whether at least one of the plurality of STOs is generating a signal in a specified frequency band, wherein either (a) presence of the signal in the specified frequency band indicates presence of the MNP or (b) presence of the signal in the specified frequency band indicates absence of the MNP; and
based at least in part on the determination of whether the at least one of the plurality of STOs is generating the signal in the specified frequency band, determining whether the labeled nucleotide precursor has been detected.
11 . The method of claim 10 , wherein determining whether the at least one of the plurality of STOs is generating the signal in the specified frequency band comprises:
detecting a presence or absence of a signal at an output of a super-heterodyne circuit coupled to the at least one of the plurality of STOs.
12 . The method of claim 10 , further comprising:
before adding the labeled nucleotide precursor to the fluidic channel of the detection device, binding at least one nucleic acid strand to a binding site in the fluidic channel, and adding, to the fluidic channel, an extendable primer and a plurality of molecules of nucleic acid polymerase.
13 . The method of claim 10 , further comprising:
in response to determining that the labeled nucleotide precursor has been detected, recording (a) an identity of the nucleotide precursor, or (b) an identity of a base complementary to the labeled nucleotide precursor.
14 . An apparatus for molecule detection, the apparatus comprising:
at least one fluidic channel;
a plurality of spin torque oscillators (STOs), each of the plurality of STOs configured to:
(a) generate a radio-frequency (RF) signal in a specified frequency band in response to detecting a magnetic nanoparticle (MNP) labeling a molecule to be detected within the at least one fluidic channel, or
(b) cease to generate the RF signal in the specified frequency band in response to detecting the MNP labeling the molecule to be detected within the at least one fluidic channel;
means for determining whether at least one of the plurality of STOs is generating the RF signal in the specified frequency band; and
means for determining, in response to determining whether the at least one of the plurality of STOs is generating the RF signal in the specified frequency band, that the molecule to be detected has or has not been detected.
15 . The apparatus recited in claim 14 , wherein the means for determining whether the at least one of the plurality of STOs is generating the RF signal comprises a super-heterodyne circuit coupled to the at least one of the plurality of STOs.
16 . The apparatus recited in claim 14 , wherein the means for determining whether the at least one of the plurality of STOs is generating the RF signal is configured to apply a DC current to the at least one of the plurality of STOs.
17 . The apparatus recited in claim 14 , wherein the means for determining whether the at least one of the plurality of STOs is generating the RF signal comprises a reference oscillator configured to generate a reference signal.
18 . The apparatus recited in claim 17 , wherein a frequency of the reference signal is selectable, and wherein the means for determining whether the at least one of the plurality of STOs is generating the RF signal is configured to select the frequency of the reference signal to substantially match an expected oscillation frequency of the RF signal.
19 . The apparatus recited in claim 14 , wherein the means for determining whether the at least one of the plurality of STOs is generating the RF signal is configured to mix a signal output from the at least one of the plurality of STOs with a reference signal.
20 . The apparatus recited in claim 14 , wherein the means for determining, in response to determining whether the at least one of the plurality of STOs is generating the RF signal, that the molecule to be detected has or has not been detected comprises a processor.