U.S. patent application number 12/637245 was filed with the patent office on 2010-07-22 for method of electrically detecting biomolecule.
This patent application is currently assigned to SAMSUNG ELECTRONICS CO. LTD.. Invention is credited to Soo-hyung CHOI, Sung-ouk JUNG, Jun-hong MIN, Ji-na NAMGOONG, Jeo-young SHIM, Kyu-tae YOO.
Application Number | 20100181209 12/637245 |
Document ID | / |
Family ID | 37177303 |
Filed Date | 2010-07-22 |
United States Patent
Application |
20100181209 |
Kind Code |
A1 |
YOO; Kyu-tae ; et
al. |
July 22, 2010 |
METHOD OF ELECTRICALLY DETECTING BIOMOLECULE
Abstract
Provided is a method of sensing biomolecules using a bioFET, the
method including: forming a layer including Au on a gate of the
bioFET; forming a probe immobilized on a substrate separated from
the gate by a predetermined distance, and a biomolecule having a
thiol group (--SH) which is incompletely bonded to the probe;
reacting the probe with a sample including a target molecule; and
measuring a current flowing in a channel region between a source
and a drain of the bioFET.
Inventors: |
YOO; Kyu-tae; (Seoul,
KR) ; JUNG; Sung-ouk; (Suwon-si, KR) ; MIN;
Jun-hong; (Yongin-si, KR) ; NAMGOONG; Ji-na;
(Yongin-si, KR) ; CHOI; Soo-hyung; (Hwaseong-si,
KR) ; SHIM; Jeo-young; (Yongin-si, KR) |
Correspondence
Address: |
CANTOR COLBURN, LLP
20 Church Street, 22nd Floor
Hartford
CT
06103
US
|
Assignee: |
SAMSUNG ELECTRONICS CO.
LTD.
Suwon-si
KR
|
Family ID: |
37177303 |
Appl. No.: |
12/637245 |
Filed: |
December 14, 2009 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
11345790 |
Feb 2, 2006 |
7659149 |
|
|
12637245 |
|
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Current U.S.
Class: |
205/775 |
Current CPC
Class: |
G01N 33/54306
20130101 |
Class at
Publication: |
205/775 |
International
Class: |
G01N 27/26 20060101
G01N027/26 |
Foreign Application Data
Date |
Code |
Application Number |
Feb 3, 2005 |
KR |
10-2005-0010183 |
Claims
1. A method of sensing biomolecules in an electrolyte using a
bioFET, the method comprising: (a) immobilizing a first probe on a
layer comprising Au on a gate of the bioFET; (b) supplying a second
probe to which a liposome containing a thiol group (--SH) compound
is bonded; (c) reacting a target molecule-containing sample with
the first probe and the second probe, and then washing the result;
(d) bursting the liposome; and (e) measuring a current flowing in a
channel region between a source and drain of the bioFET.
2. The method of claim 1, wherein the target is DNA, RNA, or a
protein.
3. The method of claim 1, wherein a portion of the target
complementarily corresponds to the first probe and another portion
of the target complementarily corresponds to the second probe.
4. The method of claim 1, wherein the thiol group compound is one
of mercaptohexanol and cysteine.
5. The method of claim 1, wherein, in operation (d), the liposome
is burst due to a gradient in osmotic pressure.
6. The method of claim 1, wherein the flow of the current in
operation (e) is generated by bonding of a thiol group, which is
released by the burst of the liposome in operation (d), with Au
formed on the surface of the gate.
Description
CROSS-REFERENCE TO RELATED PATENT APPLICATIONS
[0001] This application is a divisional of U.S. application Ser.
No. 11/345,790, filed Feb. 2, 2006, which claims the benefit of
Korean Patent Application No. 10-2005-0010183, filed on Feb. 3,
2005, in the Korean Intellectual Property Office, the contents of
which in their entirety are herein incorporated by reference.
BACKGROUND OF THE INVENTION
[0002] 1. Field of the Invention
[0003] The present invention relates to a method of detecting a
biomolecule using a field effect transistor (FET), and more
particularly, to a method of electrically sensing a bond between a
probe biomolecule and a target biomolecule.
[0004] 2. Description of the Related Art
[0005] Biosensors, which include transistors, are sensors that
electrically sense biomolecules. Biosensors are manufactured using
semiconductor processes, quickly convert electric signals, and can
be easily applied to integrated circuits (ICs) and MEMS. Due to
these advantages, much research has gone into biosensors.
[0006] U.S. Pat. No. 4,238,757 was the first patent regarding the
detection of biological reactions using a FET, and is directed to a
biosensor capable of identifying an antigen-antibody reaction by
detecting a current that varies due to a change in the surface
charge concentration of a semiconductor inversion layer. This
patent is directed toward a biosensor for sensing proteins. In U.S.
Pat. No. 4,777,019 biological monomers are adsorbed onto the
surface of a gate, and hybridization between the biological
monomers and complementary monomers is measured using a FET. U.S.
Pat. No. 5,846,708 discloses a method of sensing hybridization
using a charged coupled device (CCD). In this method, the
hybridization can be identified using a phenomenon that bonded
biomolecules absorb light. In U.S. Pat. Nos. 5,466,348 and
6,203,981, a TFT is used and a S/N ratio is improved by application
to a circuit.
[0007] A thin film transistor (TFT) has lower manufacturing costs
than a transistor formed on a silicon substrate, and a TFT enables
the formation of an array-type chip with increased integrity by
increasing the area of a substrate. An FET used as a biosensor has
lower costs and requires less time than other conventional methods.
In addition, an FET can be easily applied to integrated circuit
(IC)/MEMS processes.
[0008] FIG. 1 is a sectional view of a typical bioFET. Referring to
FIG. 1, a source 12a and a drain 12b are respectively formed in
side portions of a substrate 11 doped with an n- or p-type
material. The source 12a and the drain 12b are of an opposite
conductivity type to the substrate 11. A gate 13 contacting the
source 12a and the drain 12b is formed on the substrate 11. The
gate 13 typically includes an oxidized layer 14, a poly silicon
layer 15, and a metal layer 16. A probe biomolecule 17 is bonded to
the metal layer 16 of the gate 13. When a predetermined target
biomolecule is bonded to the probe biomolecule 17 by, for example,
hydrogen bonding, the current changes. The change in the current is
measured and the bonding of the probe biomolecule 17 and the
predetermined target biomolecule can be identified.
[0009] The above-described conventional techniques, however, cannot
retain reliable accuracy and be reliably reproduced when charged
biomolecules are sensed in an electrolyte 10. In detail, the target
biomolecule is bonded to the probe biomolecule 17 immobilized on
the surface of the gate 13 in an electrolyte of a bioFET. At this
time, when charged biomolecules are separated from the surface of
the gate 13 by a debye length or farther, the charged biomolecules
cannot affect an electric potential at the surface of the gate 13
due to ionic shielding of ions adjacent to biomolecules in the
electrolyte 10, and it is difficult to accurately measure the
electrical potential of the surface of the gate 13. Accordingly,
the detection of immobilization of the probe biomolecule 17 to the
surface of the gate 13 and hybridization of the probe biomolecule
17 with the target biomolecule has low reproducibility and
accuracy.
[0010] In order to prevent ionic shielding, ionic concentration of
the electrolyte can be decreased to increase the debye length.
However, when the ionic concentration is decreased, for example,
when the concentration of NaCl is 0.01 M or less, the detection
efficiency decreases.
[0011] U.S. Pat. No. 5,466,348 discloses an apparatus for sensing
biomolecules in a dry environment to prevent ion shielding.
However, practical use of the apparatus is limited and a separate
apparatus is required.
[0012] In U.S. Pat. No. 6,203,981, two transistor are used to
decrease noise, and thus, increase the S/N ratio. However, desired
effects of signal amplification cannot be obtained.
[0013] In U.S. Pat. No. 6,482,639 B2, charged biomolecules and
uncharged biomoleclues are detected through a change in capacitance
due to adsorbtion/bonding of biomolecules between a reference
electrode and a gate surface. However, reproducibility and accuracy
for sensing using a bioFET are not reliable.
SUMMARY OF THE INVENTION
[0014] The present invention provides a method of detecting
biomolecules using a bio field effect transistor (FET). By using
the method, the hybridization of a probe biomolecule with a target
biomolecule at the surface of a bioFET can be accurately detected
and high signal amplification can be obtained.
[0015] According to an aspect of the present invention, there is
provided a method of sensing biomolecules in an electrolyte using a
bio field effect transistor (FET), the method including: (a)
forming a layer comprising Au on a gate of the bioFET; (b) forming
a probe immobilized to a substrate separated from the gate by a
predetermined distance, and a biomolecule having a thiol group
(--SH), which is incompletely bonded to the probe; (c) reacting the
probe with a sample including a target molecule; and (d) measuring
a current flowing in a channel region between a source and a drain
of the bioFET.
[0016] The biomolecule, the probe, or the target may be DNA, RNA,
or a protein.
[0017] A bonding force between the probe and the target molecule
may be greater than a bonding force between the probe and the thiol
group-containing biomolecule.
[0018] In operation (c), the biomolecule may be separated from the
probe when the target molecule is bonded to the probe.
[0019] In operation (d), the flow of the current may be formed by
bonding of the thiol group of the biomolecule with Au on the
surface of the gate.
[0020] The incomplete bonding in operation (b) may be formed by the
biomolecule whose bonding force with the probe is weaker than the
bonding force between the probe and the target biomolecule.
[0021] According to another aspect of the present invention, there
is provided a method of sensing biomolecules in an electrolyte
using a bioFET, the method including: (a) immobilizing a first
probe to a layer comprising Au on a gate of the bioFET; (b)
supplying a second probe to which a liposome containing a thiol
group (--SH) compound is bonded; (c) reacting a target
molecule-containing sample with the first probe and the second
probe, and then washing the result; (d) bursting the liposome; and
(e) measuring a current flowing in a channel region between a
source and a drain of the bioFET.
[0022] The first probe, the second probe, or the target is DNA,
RNA, or a protein.
[0023] A portion of the target may complementarily correspond to
the first probe and another portion of the target may
complementarily correspond to the second probe.
[0024] The thiol group compound may be any compound having a thiol
group, and may be mercaptohexanol or cysteine. In addition, the
thiol group compound may be any compound including an anionic
molecule, and may be aspartate or glutamate.
[0025] The burst of the liposome in operation (d) can be made using
any methods, preferably, using the difference of osmotic
pressure.
[0026] The flow of the current in operation (e) may be generated by
bonding of a thiol group, which is released by the burst of the
liposome in operation (d), with Au formed on the surface of the
gate.
BRIEF DESCRIPTION OF THE DRAWINGS
[0027] The above and other features and advantages of the present
invention will become more apparent by describing in detail
exemplary embodiments thereof with reference to the attached
drawings in which:
[0028] FIG. 1A is a sectional view of a typical bio field effect
transistor (FET);
[0029] FIG. 1B illustrates the structure and debye length of a
typical bioFET;
[0030] FIG. 1C is a graph of the drain current change of the bioFET
of FIG. 1B measured using a Kethley 4200;
[0031] FIG. 2 illustrates a method according to an embodiment of
the present invention;
[0032] FIG. 3 illustrates a method according to another embodiment
of the present invention;
[0033] FIG. 4 is a graph of current flowing in a channel between a
source and a drain when a target is detected using the method
illustrated in FIG. 2; and
[0034] FIG. 5 is a graph of current flowing in a channel between a
source and a drain when a target is detected using the method
illustrated in FIG. 3.
DETAILED DESCRIPTION OF THE INVENTION
[0035] A basic principle of the present invention will now be
described.
[0036] FIGS. 1A through 1C relate to a conventional bio field
effect transistor (FET). Referring to FIG. 1A, a probe DNA 17 is
immobilized on a gate 13 of a bioFET installed in an electrolyte
10. A source 12a and a drain 12b, which are composed of a
predetermined material, are formed on side portions of a substrate
11, respectively. The gate 13 contacts the source 12a and the drain
12b and is formed on the substrate 11. Although the structure of
the gate 13 is not limited, the gate 13 generally includes a gate
insulating layer 14, a gate electrode layer 15, and a metal
material layer 16, to which the probe DNA 17 is immobilized.
[0037] When the DNA immobilizes on the surface of the gate 13 of
the bioFET, the surface charge density changes, and thus, a current
flowing in a channel region of the substrate 11 is changed.
Immobilization of the probe DNA 17 and hybridization of a target
and the probe DNA 17 can be detected according to the change in the
current.
[0038] Referring to FIG. 1A, probe biomolecules, for example, probe
DNAs 17, are charged and immobilized on the substrate 11. As the
number of immobilized probe DNAs 17 increases, the surface charge
density increases, and thus, more current flows in the channel
between the source 12a and the drain 12b. Potential damping of
charged biomolecules due to ionic shielding in the electrolyte 10
is dependent on the debye length. That is, the degree to which the
bioFET channel region is effectively affected may vary according to
the debye length of immobilized or hybridized charged
biomolecules.
[0039] The entire surface of a typical FET, excluding the gate 13,
is subjected to passivation to prevent ionic diffusion in the
electrolyte 10. The gate 13 is coated with, for example, Au 16, and
the probe DNA 17 is modified to have a thiol group. In this case,
the thiol group of the probe DNA 17 is bonded to the Au 16 by
self-assembly so that the probe DNA 17 is immobilized on the gate
13.
[0040] When the probe DNA 17 with the thiol group is immobilized on
the Au 16 of the gate 13 and when the probe DNA 17 immobilized on
the surface of the gate 13 is hybridized with a target molecule,
the immobilization and hybridization directly affect a current
flowing in the channel region between the source 12a and the drain
12b when a predetermined voltage is applied between the source 12a
and drain 12b of the bioFET in the electrolyte 10.
[0041] However, based on the finding by the present inventors, as
illustrated in FIGS. 1B and 1C, when the Au 16 is bonded to the
thiol group of the probe DNA 17, the bonding occurs in the vicinity
of the gate 13, and thus, the debye length does not affect the
current flowing in the channel between the source 12a and drain 12b
and the change in the current is very large. On the other hand, the
hybridization between the probe DNA 17 and the target molecule
occurs away from the gate. As a result, the current is proportional
to the negative exponential of the distance between the surface of
the gate 13 and a point where the hybridization occurs. As a
result, the change in the current when hybridization occurs is
comparatively smaller than the change in the current when the
bonding between the Au 16 and the thiol group occurs. As
illustrated in FIG. 1C, when Au 16 is bonded to the thiol group of
the probe DNA 17, the change in the current is 202 .mu.A, but when
the probe DNA 17 is hybridized with the target molecule, the change
in the current is as little as 25 .mu.A. That is, the signal
resulting from the hybridization is very weak and a S/N ratio is
too small.
[0042] In order to solve this problem, the present inventors
developed a sensing method in which a large increase of the current
can be obtained when a probe molecule is hybridized with a target
molecule. That is, in embodiments of the present invention, the
bonding of Au and a thiol group, which can induce a dramatic change
in the current, is controlled according to the hybridization
between the target molecule and the probe.
A method of sensing biomolecules in an electrolyte using a bioFET
according to a first embodiment of the present invention includes
forming a layer including Au on a gate of the bioFET; forming a
probe immobilized to a substrate separated from the gate by a
predetermined distance, and a biomolecule having a thiol group
(--SH) which is incompletely bonded to the probe; reacting the
probe with a sample including a target molecule; and measuring a
current flowing in a channel region between a source and a drain of
the bioFET.
[0043] The sensing method according to the present embodiment will
now be described in detail with reference to FIG. 2.
[0044] In a conventional method, when a bond between a probe
(containing --SH) and a target molecule is induced after the probe
is immobilized on the surface of a gate (Au), the change in the
current is much lower when the target molecule is hybridized than
when the probe is immobilized. In order to solve this problem, in
the present embodiment, a probe 28 is immobilized on a substrate 31
separated from a gate 23, and a biomomolecule 27 having a thiol
group (--SH) is incompletely bonded to the probe 28. The term
`incomplete bonding` indicates a relatively weak bond. For example,
as for complementary bonding of DNA chains, `incomplete bonding`
indicates bonding, such as mismatch, that is not complete
complementary bonding. An example of DNA enabling such incomplete
bonding is a DNA chain having a thiol group that is shorter than a
target.
[0045] When the sample including the target is added to the bioFET
in which the biomolecule 27 is incompletely bonded to the probe 28,
the biomolecule 27 having the thiol group (--SH) which is
incompletely bonded to the probe 28 is separated from the probe 28,
and the target, which can relatively completely bind (for example,
complete complementary bonding for DNA) to the probe 28, is
competitively bonded to the probe 28 instead of the thiol group
(--SH). Such a replacement by the target can occur because the
bonding force between the target and the probe is much stronger
than the bonding force between the probe and the thiol group
(--SH).
[0046] The biomolecule 27, which includes thiol group, is bonded to
Au 26 of the gate 23, and thus, the current flowing in a channel
between a source 22a and a drain 22b changes dramatically. As a
result, hybridization between the target and the probe 28 can be
sensed.
[0047] In the above method, the probe, the target, or the
biomolecule may be DNA, RNA, or a protein. The protein can be any
biomolecule, such as an antigen, an antibody, a substrate protein,
an enzyme, a coenzyme, or the like.
[0048] The bonding to the probe 28 can be any biomolecule bonding
known in the art, such as nucleic hybridization, an
antigen-antibody reaction, an enzyme bonding reaction, and the
like.
A method of sensing biomolecules in an electrolyte using a bioFET
according to a second embodiment of the present invention includes
immobilizing a first probe to a layer comprising Au on a gate of
the bioFET; supplying a second probe to which a liposome containing
a thiol group (--SH) compound is bonded; reacting a target
molecule-containing sample with the first probe and the second
probe, and then washing the result; bursting the liposome; and
measuring a current flowing in a channel region between a source
and drain of the bioFET.
[0049] The present embodiment will now be described in detail with
reference to FIG. 3.
[0050] According to the present embodiment, first, a first probe 28
is immobilized on the surface of a gate (Au). The immobilizing
method is not limited and any method known in the art can be
used.
[0051] Then, a second probe 29 to which a liposome 30 is bonded is
added to an electrolyte in which reactions occur. The liposome 30
includes a compound including a thiol group (--SH). Such a thiol
group-containing compound can be any compound having the thiol
group, such as mercaptohexane or cysteine. In addition, the thiol
group-containing compound can be a compound having an anionic
molecule. The compound having an anionic molecule can be aspartate
or glutamate.
[0052] A sample including a target is added to the bioFET. As a
result, the target is reacted with the first probe 28 and the
second probe 29 so that the target is bonded to the first probe 28
and the second probe 29. After the bonding occurs, washing is
performed to remove non-bound probes.
[0053] Thereafter, the liposome 30 is burst to release the compound
having the thiol group. The released thiol group is bonded to Au of
the gate 23, and thus, a current flows in the channel region
between a source 22a and a drain 22b. As a result, hybridization
between the target and the probes 28 and 29 can be sensed.
[0054] As described above, since the bonding of Au and --SH, which
generates strong electrical signals, can occurred according to the
hybridization of a target and a probe and the amount of the
hybridized target, more accurate sensing can be achieved.
[0055] The present invention will now be described in further
detail with reference to the following examples. These examples are
for illustrative purposes only and are not intended to limit the
scope of the present invention.
EXAMPLES
Example 1
Immobilization of DNA Probe and Hybridization Between DNA Probe and
Target DNA
[0056] 1. Immobilization of DNA Probe
[0057] As illustrated in FIG. 2, a gate 23 including an oxidized
layer 24, a polysilicon layer 25, and a metal layer (Au layer); a
p-channel bioFET was used; and a reference bioFET that did not
include the metal layer (Au layer) on the gate was used so that
biomolecules were not immobilized.
[0058] First, .gamma.-aminopropyltrietoxysilane (GAPS) was coated
on a silicon oxide pad of a silicon substrate chip 31, and a DNA
having an amino group at its 5'-end was immobilized thereon.
[0059] That is, after GAPS was spin coated on the substrate 31, a
20 .mu.M probe polynucleotide having an aminohexyl group at its
5'-end (5'-ATGACAATGAGTATGCCTA-3') (SEQ ID No. 1), which was
dissolved in 6 mM PEG (Aldrich Co., molecular weight of 10,000) in
a 0.1 M NaHCO.sub.3 pH 9 solution containing 50% DMSO, was reacted
with the GAPS film to achieve immobilization of the probe.
[0060] After the probe was immobilized, the probe was hybridized
with a DNA that was modified to complementarily correspond to a
portion of the probe and had a thiol group (hereinafter, referred
to as `a hurdle DNA` (5'-SH-TAGGCATACTCATTG-3') (SEQ ID No. 2).
Since the bioFET in another channel was blocked through a valve,
the attachment of the modified hurdle DNA containing a thiol group
to the surface of the gate of the bioFET could be prevented. After
the hybridization, non-hybridized hurdle DNAs that were not reacted
with the probe were removed by washing.
[0061] 2. Hybridization of Probe and Target DNA
[0062] The valve between a micro channel including the silicon
oxide pad to which the probe was immobilized and a micro channel
including the bioFET and the reference bioFET were opened such that
the micro channels were connected to each other, and then a 1 .mu.M
target DNA (5'-TAG GCA TAC TCA TTGTCAT-3') (SEQ ID No. 3) was added
thereto.
[0063] 3. Hybridization of Probe and Mismatch Target
[0064] The valve between a micro channel including the silicon
oxide pad to which the probe was immobilized and a micro channel
including the bioFET and a reference bioFET were opened such that
these micro channel were connected to each other, and then a 1
.mu.M mismatch target DNA (5'-TGT TCT CTT GTC TTG-3') (SEQ ID No.
4) was added thereto.
[0065] 4. Measurement Method
[0066] A voltage was applied to the bioFET and the change in
current was measured using a Kiethley 4200 parameter analyzer. -2V
was applied to the gate through a standard electrode and -2V was
applied between a source and a drain, and the current between the
drain and source was measured.
[0067] The above processes 1 through 4 were repeated three times.
The results are shown in Table 1.
TABLE-US-00001 TABLE 1 Mismatch Injection Perfect Match Injection
Experiment 1 11 .mu.A 20 .mu.A Experiment 2 2 .mu.A 25 .mu.A
Experiment 3 32 .mu.A 60 .mu.A
[0068] The average value of the results obtained from the three
experiments is shown in FIG. 4. In this case, each chip included
the bioFET and the reference bioFET, which did not include a metal
layer (Au layer) on the surface of the gate. Since the reference
bioFET did not include the Au layer, the DNA having the thiol group
was not immobilized thereon. Referring to FIG. 4, for the reference
bioFET, the addition of the mismatch DNA and the target DNA
resulted in a small change in the current. However, for the bio FET
including the Au layer, the addition of the mismatch DNA resulted
in a small current change while the addition of the match target
DNA resulted in an increase of about 20 .mu.A or more in the
current.
Example 2
Sensing Method Using Liposome
[0069] 1. Immobilization of DNA Probe
[0070] As illustrated in FIG. 3, a gate 23 was formed on an
oxidized layer 24, a polysilicon layer 25, and a metal layer (Au
layer); a p-channel bioFET was used; and a reference bioFET that
did not include a metal layer (Au layer) on a gate was used so that
biomolecules were not immobilized.
[0071] A thiol-modified probe DNA (5'-SH-ATGACAATGAGTATGCCTA-3')
(SEQ ID No. 5) was immobilized on the Au layer, the surface of the
gate, using a self assembly monolayer (SAM) method.
[0072] 2. Hybridization of Probe and Target DNA
[0073] A target gene having a liposome-epoxy at its 5' end
(liposome-epoxy-NH.sub.2-TAG GCA TAC TCA TTGTCAT-3') (SEQ ID No. 6)
was injected to the bioFET. The liposome included mercaptohexanol
(MCH).
[0074] The target gene was reacted with a probe DNA at 40.degree.
C. for 3 hours so that the target gene was hybridized with the
probe DNA.
[0075] 3. Burst of Liposome
[0076] The liposome was burst by adding methanol.
[0077] Thereafter, the current was measured in the same manner as
in Example 1. The results are shown in FIG. 5.
[0078] As shown in FIG. 5, the change in the current occurred when
an amine-modified match target gene connected to a liposome-epoxy
including mercaptohexnol was hybridized with an immobilized probe
gene and then the liposome was burst to release mercaptohexanol.
That is, the target gene connected to the liposome was added and
then methanol was added to burst the liposome. In this case, the
current was increased by about 40 .mu.A.
[0079] Based on the above experimental results, it was determined
that the liposome could be bonded to a second probe, instead of a
target, and then, the target could be added. When this was
performed, a sandwich-shaped bond was formed, as shown in FIG. 3.
The liposome was burst by the variation in osmotic pressures, and
the change in the current was measured. As a result, the presence
of a target gene was identified.
[0080] A method of sensing biomolecules in an electrolyte using a
bioFET has high signal amplification and a high S/N ratio so that
excellent reproducibility and accuracy can be attained.
[0081] While the present invention has been particularly shown and
described with reference to exemplary embodiments thereof, it will
be understood by those of ordinary skill in the art that various
changes in form and details may be made therein without departing
from the spirit and scope of the present invention as defined by
the following claims.
Sequence CWU 1
1
6119DNAArtificial Sequenceprobe DNA 1atgacaatga gtatgccta
19215DNAArtificial Sequenceprobe DNA 2taggcatact cattg
15319DNAArtificial Sequencetarget DNA 3taggcatact cattgtcat
19415DNAArtificial Sequencemismatch target DNA 4tgttctcttg tcttg
15519DNAArtificial Sequenceprobe DNA 5atgacaatga gtatgccta
19619DNAArtificial Sequencetarget DNA 6taggcatact cattgtcat 19
* * * * *