# US 2015/0147756 A1 · Sensor Device and Method for Label-Free Detecting of Nucleic Acid Sequences

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- Number: US 2015/0147756 A1
- Document ID: US20150147756A1
- Status: Published application
- Kind: A1
- Application number: 14/341,973
- Filed: 2014-07-28
- Published: 2015-05-28
- Earliest claimed: 2013-08-05
- Inventors: Frank Vollmer; Yuqiang Wu; David Zhang
- Web page: https://patentgrep.com/patent/US20150147756A1

## CPC

- C12Q 1/6825: Nucleic acid detection involving sensors
- G02B 17/004: {Systems comprising a plurality of reflections between two or more surfaces, e.g. cells, resonators (multipass arrangements for optical cuvettes G01N21/031; laser resonators H01S3/05)}
- G02B 26/001: {based on interference in an adjustable optical cavity (interference filters G02B5/28; devices or arrangements using multiple reflections in spectrometry or monochromators G01J3/26)}
- 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
- G02B: OPTICAL ELEMENTS, SYSTEMS OR APPARATUS

## Abstract

A sensor device (100), which is adapted for detecting target molecules having a target nucleic acid sequence, comprises an optical whispering gallery mode (WGM) resonator (10) having a resonance frequency, wherein the WGM resonator is functionalized with a double-strand DNA precursor compound and the 10 resonance frequency depends on a mass load provided by the double-strand precursor compound, the double-strand precursor compound is capable of a target-specific strand displacement reaction with the target molecules, and in response to the strand displacement reaction, the double-strand precursor 15 compound is capable to be partially decoupled from the WGM resonator (10), wherein the mass load can be decreased and the resonance frequency of the WGM resonator can be increased. Furthermore, a sensing method for detecting target molecules including nucleic acid sequences is described.

## Claims

### Claim 1

A sensor device, which is adapted for detecting target molecules having a target nucleic acid sequence, comprising:
an optical whispering gallery mode (WGM) resonator having a resonance frequency, wherein
the WGM resonator is functionalized with a double-strand DNA precursor compound and the resonance frequency depends on a mass load provided by the double-strand precursor compound;
the double-strand precursor compound is capable of a target-specific strand displacement reaction with the target molecules; and
in response to the strand displacement reaction, the double-strand precursor compound is capable to be partially decoupled from the WGM resonator, wherein the mass load can be decreased and the resonance frequency of the WGM resonator can be increased.

### Claim 2 (depends on 1)

The sensor device according to claim 1, wherein
the double-strand precursor compound has a primary strand and a secondary strand being hybridized with the primary strand, wherein the secondary strand is connected with the WGM resonator; and
the double-strand precursor compound is capable to be partially decoupled from the WGM resonator by replacing the secondary strand by the target molecule and dissociating the primary strand with the target molecule from the WGM resonator.

### Claim 3 (depends on 1)

The sensor device according to claim 1, wherein
the double-strand precursor compound (SBP) has a primary strand (B), a first secondary strand (P) being hybridized with the primary strand (B) and a second secondary strand (S) being hybridized with the primary strand (B), wherein
the first secondary strand (P) is connected with the WGM resonator, and
the double-strand precursor compound (SBP) is capable to replace the second secondary strand (S) by the target molecule (C), and
the double-strand precursor compound (SBP) is capable to replace the first secondary strand (P) by a further single-strand precursor compound (F) and to dissociate the primary strand (B) hybridized with the target molecule (C) and the single-strand precursor (F) compound from the WGM resonator.

### Claim 4 (depends on 3)

The sensor device according to claim 3, wherein
the single-strand precursor molecule (F) is capable to replace the target molecule from the primary strand, so that the target molecule is released.

### Claim 5

The sensor device according to one of the foregoing claims, —the WGM resonator is provided with at least one optical waveguide or optical prism being arranged for at least one of in-coupling sample light into the WGM resonator and out-coupling resonator light out of the WGM resonator.

### Claim 6 (depends on 5)

The sensor device according to claim 5, further comprising
a continuous wave tunable laser source being arranged for generating the sample light.

### Claim 7 (depends on 1)

The sensor device according to claim 1, further comprising
a sample cell being arranged for accommodating the WGM resonator and a sample liquid to be investigated.

### Claim 8 (depends on 1)

The sensor device according to claim 1, wherein
the WGM resonator has a surface layer made of a biotin streptavidin compound to which the double-strand precursor compound is coupled.

### Claim 9

A sensing method for detecting target molecules including nucleic acid sequences, comprising:
providing an optical whispering gallery mode (WGM) resonator having a resonance frequency, wherein the WGM resonator is functionalized with a double-strand precursor compound and the resonance frequency depends on a mass load provided by the double-strand precursor compound, wherein
the double-strand precursor compound is capable of a strand displacement reaction with the target molecules;
the double-strand precursor compound is capable to be partially decoupled from the WGM resonator; and
the mass load can be decreased and the resonance frequency of the WGM resonator can be increased in response to the strand displacement reaction,
contacting a sample liquid to be investigated with the WGM resonator;
monitoring the resonance frequency of the WGM resonator; and
detecting the target molecules if the resonance frequency of the WGM resonator is increased.

### Claim 10 (depends on 9)

The sensing method according to claim 9, wherein
the double-strand precursor compound has a primary strand and a secondary strand being hybridized with the primary strand, wherein the secondary strand is connected with the WGM resonator; and
the strand displacement reaction comprises partially decoupling the double-strand precursor compound from the WGM resonator by replacing the secondary strand by the target molecule and dissociating the primary strand with the target molecule from the WGM resonator.

### Claim 11 (depends on 9)

The sensing method according to claim 9, wherein
the double-strand precursor compound (SBP) has a primary strand (B), a first secondary strand (P) being hybridized with the primary strand (B) and a second secondary strand (S) being hybridized with the primary strand (B), wherein the first secondary strand (P) is connected with the WGM resonator, wherein the strand displacement reaction comprises:
a first step of replacing the second secondary strand (S) by the target molecule (C), and
a second step of replacing the first secondary strand (P) by a further single-strand precursor molecule (F) and dissociating the primary strand (B) hybridized with the target molecule (C) and the single-strand precursor (F) compound from the WGM resonator.

### Claim 12 (depends on 11)

The sensing method according to claim 11, wherein the strand displacement reaction comprises:
a third step of replacing the target molecule from the primary strand, so that the target molecule is released.
