High density and multiplexed nanopore devices with transverse tunneling junction for biomolecule detection and sequencing
View Patent ↗Disclosed are systems and methods for delivering and/or linking molecules, such as DNA, between tunable metal nanogaps and measuring electrical and/or optical properties. In one example, disclosed are high density multiplexed chips with a plurality of groups, each group including a plurality of nanodevices, the chips capable of coupling to one or more multiwell structures for providing samples to each individual group. In this way, the chips can be used for high-throughput analysis of molecules such as DNA.
1. A chip for measuring electrical and/or optical properties from one or more molecules, comprising:
a plurality of electronic devices, each of the plurality of electronic devices comprising:
a top fluidic channel/chamber and a bottom fluidic channel/chamber fabricated in a planar substrate, the top fluidic channel/chamber being sealed at a bottom of the electronic device and including a first open window at a top of the electronic device, and the bottom fluidic channel/chamber being sealed at the top of the electronic device and including a second open window at the bottom of the electronic device,
a first electrode and a second electrode positioned in a space of the electronic device between the top fluidic channel/chamber and the bottom fluidic channel/chamber, and
a nanogap having dimensions defined in part by a distance between the first electrode and the second electrode, the nanogap having a single path for a molecule to travel from the top fluidic channel/chamber to the bottom fluidic channel/chamber and/or from the bottom fluidic channel/chamber to the top fluidic channel/chamber,
wherein the distance is between about 1-100 nm, and wherein the nanogap has a narrowest bottleneck in the single path between the top fluidic channel/chamber and the bottom fluidic channel,
wherein the plurality of electronic devices are divided into a set number of different groups, and
wherein the chip further comprises one or more multiwell structures coupled to the chip, with individual wells of the one or more multiwell structures corresponding to each of the set number of different groups.
2. The chip of claim 1 , wherein, for a first electronic device of the plurality of electronic devices, the distance is defined via the first and the second electrodes being electrochemically deposited under feedback control with one or more metal materials within the top fluidic channel/chamber and/or the bottom fluidic channel/chamber, thereby forming the single path.
3. The chip of claim 2 , wherein, for the first electronic device, the planar substrate is a transparent substrate.
4. The chip of claim 3 , wherein, for the first electronic device, the transparent substrate is glass or quartz.
5. The chip of claim 2 , wherein, for the first electronic device, the planar substrate is a non-transparent substrate.
6. The chip of claim 5 , wherein, for the first electronic device, the planar substrate is silicon coated with SiO 2 and/or Si 3 N 4 .
7. The chip of claim 2 , wherein, for the first electronic device, the first electrode and the second electrode are formed of gold, palladium, platinum, or another noble metal or alloy compatible with top-down lithography and electrochemical deposition, or combinations thereof.
8. The chip of claim 2 , wherein, for the first electronic device, the space in which the first electrode and the second electrode are positioned is formed at least in part by one or more dielectric layers.
9. The chip of claim 8 , wherein, for the first electronic device, the one or more dielectric layers is HfO 2 , ZrO 2 , SiO 2 , Si 3 N 4 , or a combination thereof.
10. The chip of claim 8 , further comprising wherein the first electronic device further comprises an additional layer of polymer dielectric for sealing.
11. The chip of claim 10 , wherein, for the first electronic device, the additional layer of polymer dielectric comprises one or more of SU-8 polymer and parylene.
12. The chip of claim 11 , wherein, for the first electronic device, the one or more dielectric layers with or without the additional layer of polymer dielectric is about 100 nm to about 100 μm.
13. The chip of claim 2 , wherein, for the first electronic device, the one or more metal materials are Ni, Co, gold, palladium, platinum, iridium, alloys thereof or combinations thereof.
14. The chip of claim 13 , wherein, for the first electronic device, the first and second electrodes being electrochemically deposited with the one or more metal materials under feed-back control further comprises a pulsed electrochemical deposition operation with a pulse width of 50 ms or less and a rest period of between about 500 ms and 2 seconds between pulses.
15. The chip of claim 2 , wherein the molecule is DNA.
16. The chip of claim 1 , wherein, for a first electronic device of the plurality of electronic devices, the nanogap is self-aligned.
17. The chip of claim 1 , wherein the number of the plurality of electronic devices is between 2-1000.
18. The chip of claim 1 , wherein the number of the plurality of electronic devices is between 1000-10,000.
19. The chip of claim 1 , wherein the number of the plurality of electronic devices is greater than 10,000.
20. The chip of claim 1 , wherein the one or more multiwell structures further comprises a first multiwell structure that couples to a top-side of the chip for providing samples to the top fluidic channel/chamber of each of the plurality of electronic devices; and/or
a second multiwell structure that couples to a bottom-side of the chip for receiving the samples provided to the top fluidic channel/chamber following translocation of an analyte within each of the samples to the bottom fluidic channel/chamber.
21. A method, using an electronic device, to measure electronic and/or optical properties from one or more molecules, the electronic device comprising:
a top fluidic channel/chamber and a bottom fluidic channel/chamber fabricated in a planar substrate, the top fluidic channel/chamber being sealed at a bottom of the electronic device and including a first open window at a top of the electronic device, and the bottom fluidic channel/chamber being sealed at the top of the electronic device and including a second open window at the bottom of the electronic device;
a first electrode and a second electrode positioned in a space of the electronic device between the top fluidic channel/chamber and the bottom fluidic channel/chamber; and
a nanogap having dimensions defined in part by a distance between the first electrode and the second electrode, the nanogap having a single path for a molecule to travel from the top fluidic channel/chamber to the bottom fluidic channel/chamber and/or from the bottom fluidic channel/chamber to the top fluidic channel/chamber,
wherein the distance is between about 1-100 nm, and wherein the nanogap has a narrowest bottleneck in the single path between the top fluidic channel/chamber and the bottom fluidic channel,
wherein the method comprises:
detecting with the electronic device of an individual mounting and/or translocation event of the one or more molecules by correlating an ionic current between the top fluidic channel/chamber and the bottom fluidic channel/chamber, and a tunneling current between the first and second electrodes through the nanogap; and
performing electrical and/or optical characterization of at least one of the one or more molecules,
wherein the planar substrate is a transparent substrate, and
wherein the performing electrical and/or optical characterization includes performing Raman spectroscopy by performing tip-enhanced Raman spectroscopy through the transparent substrate to characterize a dynamic structure of the at least one of the one or more molecules.
22. The method of claim 21 , wherein the performing electrical and/or optical characterization includes determining a sequence corresponding to the at least one of the one or more molecules.
23. The method of claim 21 , wherein the distance is defined via the first and the second electrodes being electrochemically deposited under feedback control with one or more metal materials within the top fluidic channel/chamber and/or the bottom fluidic channel/chamber, thereby forming the single path.
24. A chip for measuring electrical and/or optical properties from one or more molecules, comprising:
a plurality of electronic devices, each of the plurality of electronic devices comprising:
a top fluidic channel/chamber and a bottom fluidic channel/chamber fabricated in a planar substrate, the top fluidic channel/chamber being sealed at a bottom of the electronic device and including a first open window at a top of the electronic device, and the bottom fluidic channel/chamber being sealed at the top of the electronic device and including a second open window at the bottom of the electronic device,
a first electrode and a second electrode positioned in a space of the electronic device between the top fluidic channel/chamber and the bottom fluidic channel/chamber, and
a nanogap having dimensions defined in part by a distance between the first electrode and the second electrode, the nanogap having a single path for a molecule to travel from the top fluidic channel/chamber to the bottom fluidic channel/chamber and/or from the bottom fluidic channel/chamber to the top fluidic channel/chamber,
wherein the distance is between about 1-100 nm, and wherein the nanogap has a narrowest bottleneck in the single path between the top fluidic channel/chamber and the bottom fluidic channel,
wherein the plurality of electronic devices are divided into a set number of different groups, and
wherein the chip further comprises one or more multiplexers for collecting signals from electronic devices corresponding to each of the set number of different groups.
25. The chip of claim 24 , wherein, for a first electronic device of the plurality of electronic devices, the distance is defined via the first and the second electrodes being electrochemically deposited under feedback control with one or more metal materials within the top fluidic channel/chamber and/or the bottom fluidic channel/chamber, thereby forming the single path.
26. A system for high-throughput analysis of single molecules, comprising:
a chip for measuring electrical and/or optical properties from one or more molecules, the chip comprising:
a plurality of electronic devices, each of the plurality of electronic devices comprising:
a top fluidic channel/chamber and a bottom fluidic channel/chamber fabricated in a planar substrate, the top fluidic channel/chamber being sealed at a bottom of the electronic device and including a first open window at a top of the electronic device, and the bottom fluidic channel/chamber being sealed at the top of the electronic device and including a second open window at the bottom of the electronic device,
a first electrode and a second electrode positioned in a space of the electronic device between the top fluidic channel/chamber and the bottom fluidic channel/chamber, and
a nanogap having dimensions defined in part by a distance between the first electrode and the second electrode, the nanogap having a single path for a molecule to travel from the top fluidic channel/chamber to the bottom fluidic channel/chamber and/or from the bottom fluidic channel/chamber to the top fluidic channel/chamber,
wherein the distance is between about 1-100 nm, and wherein the nanogap has a narrowest bottleneck in the single path between the top fluidic channel/chamber and the bottom fluidic channel, and
wherein the plurality of electronic devices are divided into a set number of different groups;
a fluidics device capable of delivering individual samples to each of the set number of different groups; and
a controller for storing instructions in non-transitory memory that, when executed, cause the controller to:
instruct the fluidics device to provide individual samples to one or more of the set number of different groups; and
following the providing of individual samples, record data comprising one or more of ionic current between the top fluidic channel/chamber and the bottom fluidic channel/chamber, tunneling current between the first electrode and the second electrode, and an optical signal from each electronic device of the set number of different groups, the data corresponding to individual mounting and/or translocation events of individual molecules within the electronic devices of the set number of different groups.
27. The system of claim 26 , wherein, for a first electronic device of the plurality of electronic devices, the distance is defined via the first and the second electrodes being electrochemically deposited under feedback control with one or more metal materials within the top fluidic channel/chamber and/or the bottom fluidic channel/chamber, thereby forming the single path.