BIOMOLECULAR SENSORS AND METHODS
Electronic sensors configured to detect single molecule targets and methods of using and manufacturing such electronic sensors are disclosed. A sensor may include a first electrode and a second electrode separated by a sensor gap. The first and second electrodes can be coupled by a sensor complex that can include a biopolymer bridge molecule and a probe. The probe can interact with a target molecule, and interaction of the probe and target molecule can produce a signal suitable to provide detection of the target molecule.
1 . A sensor device comprising:
a first contact coupled to a first electrode;
a second contact coupled to a second electrode;
a sensor gap defined between one of the first contact and the first electrode and one of the second contact and the second electrode; and
a bridge molecule comprising a first end and a second end; wherein the bridge molecule comprises a biopolymer, and wherein the bridge molecule is coupled to the first contact at the first end and coupled to the second contact at the second end; and
a probe molecule coupled to the biopolymer to form a sensor complex,
wherein the probe molecule is coupled to the biopolymer by a precisely positioned linker.
2 . The sensor of claim 1 , wherein the biopolymer bridge molecule has an atomically precise attachment point for a probe molecule.
3 . The sensor device of claim 1 , wherein the sensor gap has a sensor gap dimension of between about 5 nm and about 30 nm.
4 . The sensor device of claim 1 , wherein the first end comprises a first self-assembling anchor and the second end comprises a second self-assembling anchor.
5 . The sensor device of claim 1 , wherein the biopolymer bridge molecule comprises a linear biopolymer.
6 . The sensor device of claim 5 , wherein the linear biopolymer comprises an end-to-end length that is less than a persistence length of the linear biopolymer.
7 . The sensor device of claim 5 , wherein the linear biopolymer comprises an end-to-end length configured to approximate a sensor gap dimension of between about 5 nm and about 30 nm.
8 . The sensor device of claim 1 , further comprising a probe, wherein the probe is attached to the biopolymer bridge molecule by a precisely positioned linker of predetermined length, and whereby the probe is configured to engage a target molecule.
9 . The sensor device of claim 8 , wherein the probe comprises an enzyme configured to engage the target molecule.
10 . The sensor device of claim 9 , wherein the enzyme is a polymerase or a reverse transcriptase.
11 . A sensor device comprising:
a first electrode overlying a substrate surface;
a second electrode overlying the substrate surface;
a sensor gap defined between the first electrode and the second electrode; and
a bridge molecule comprising a first end and a second end; wherein the sensor gap comprises a sensor gap dimension of between about 5 nm and about 30 nm; wherein the bridge molecule comprises a biopolymer bridge molecule; and wherein the bridge molecule is coupled to the first contact at the first end and coupled to the second contact at the second end.
12 . The sensor device of claim 11 , wherein the biopolymer bridge molecule has an atomically precise attachment point for a probe molecule.
13 . The sensor device of claim 11 , wherein the first end comprises a first self-assembling anchor and the second end comprises a second self-assembling anchor.
14 . The sensor device of claim 11 , wherein the biopolymer bridge molecule comprises a linear biopolymer.
15 . The sensor device of claim 14 , wherein the linear biopolymer comprises an end-to-end length that is less than a persistence length of the linear biopolymer.
16 . The sensor device of claim 15 , wherein the linear biopolymer comprises an end-to-end length configured to approximate a sensor gap dimension of between about 5 nm and about 30 nm.
17 . The sensor device of claim 11 , further comprising a probe, wherein the probe is attached to the biopolymer bridge molecule by a linker, and wherein the probe is configured to engage a target molecule.
18 . The sensor device of claim 17 , wherein the probe comprises an enzyme configured to engage the target molecule.
19 . The sensor device of claim 18 , wherein the enzyme is a polymerase or a reverse transcriptase.
20 . The sensor device of claim 11 , wherein the biopolymer bridge molecule comprises a nucleic acid duplex.
21 . The sensor device of claim 20 , wherein the nucleic acid duplex comprises a DNA duplex, a DNA-RNA hybrid duplex, a DNA-PNA hybrid duplex, a PNA-PNA duplex, or a DNA-LNA hybrid duplex.
22 . The sensor device of claim 20 , wherein the nucleic acid duplex comprises a thiol-modified oligonucleotide.
23 . The sensor device of claim 13 , wherein one of the first self-assembling anchor and the second self-assembling anchor comprises a 5′-thiol modification
24 . The sensor device of claim 20 , wherein the nucleic acid duplex further comprises an internal modification.
25 . The sensor device of claim 13 , wherein the biopolymer bridge comprises a peptide sequence, and wherein one of the first self-assembling anchor and the second self-assembling anchor comprises a cysteine residue or a peptide configured to selectively bind gold, aluminum, silicon dioxide, or other specific metals or material contacts.
26 . The sensor device of claim 17 , wherein the probe is an enzyme configured to engage the target molecule during a reaction in a solution comprising a plurality of different target molecules, wherein the reaction comprises a time period t, and wherein contacting the target molecule produces a plurality of conformational changes in the enzyme in response to the plurality of target molecule features, wherein each of the plurality of conformational changes modulates an electrical measurement in the sensor to produce a signal feature.
27 . The sensor device of claim 26 , further comprising a signal processing system configured to detect the signal feature.
28 . The sensor device of claim 26 , wherein the sensor device is configured to produce a signal trace comprising a plurality of signal features detected over time period t.
29 . The sensor device of claim 11 , further comprising a signal interpretation device, wherein the signal interpretation device comprises a signal interpretation map, and wherein the signal interpretation map is calibrated against a signal trace from a known target sequence.
30 . A method of manufacturing a sensor device comprising:
(a) forming a first electrode and a second electrode on a substrate surface, wherein the first electrode and the second electrode are separated by a sensor gap;
(b) placing a first contact on the first electrode and a second contact on the second electrode, wherein the first contact and the second contact are separated by a contact gap; and
(c) attaching a bridge molecule to the first contact and the second contact.