IP Library › Granted Patent US 12,276,653
Granted Patent B2
US 12,276,653 · App. 17/333,087 · Granted Apr 15, 2025

Bioelectronic devices with programmable adaptors

Inventor: Stuart Lindsay (Phoenix, AZ)
Assignee: Arizona Board of Regents on behalf of Arizona State University
G01N33/48721C12Q1/005G01N27/3273
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Quick Facts
Patent No.
US 12,276,653
App. No.
17/333,087
Granted
Apr 15, 2025
Kind
B2
Abstract

The present disclosure provides devices, systems, and methods related to bioelectronic devices. In particular, the present disclosure provides bioelectronic devices, and methods of making bioelectronic devices, comprising adjustable adaptor polypeptides with repeatable motifs and enhanced conductive properties. The bioelectronic devices and methods of the present disclosure are useful for a variety of applications, including the direct measurement of protein activity (e.g., when sequencing a biopolymer).

Claims (42)

1. A bioelectronic device comprising:

a first electrode and a second electrode separated by a gap;

a protein attached to the first and second electrodes via a linker; and

at least one adaptor polypeptide coupled to the protein, thereby stabilizing the protein within the gap;

wherein the at least one adaptor polypeptide comprises at least one repeatable motif, wherein the number of repeatable motifs is adjustable based on the size of the gap between the first and second electrodes.

2. The bioelectronic device of claim 1 , wherein the at least one adaptor polypeptide comprises two adaptor polypeptides, each adaptor polypeptide coupled to the protein at difference positions on the protein.

3. The bioelectronic device of claim 1 , wherein the at least one adaptor polypeptide comprises a hydrophobic core.

4. The bioelectronic device of claim 1 , wherein the at least one adaptor polypeptide comprises a hydrophilic exterior.

5. The bioelectronic device of claim 1 , wherein the at least one repeatable motif comprises an α-helix and/or a β-sheet.

6. The bioelectronic device of claim 1 , wherein the at least one repeatable motif comprises at least two α-helices.

7. The bioelectronic device of claim 1 , wherein the at least one repeatable motif comprises a β-barrel.

8. The bioelectronic device of claim 1 , wherein the at least one adaptor polypeptide comprises at least one aromatic amino acid positioned within its hydrophobic core.

9. The bioelectronic device of claim 8 , wherein the at least one aromatic amino acid is tyrosine, tryptophan, or phenylalanine.

10. The bioelectronic device of claim 1 , wherein the at least one adaptor polypeptide comprises at least one amino acid substitution from a non-aromatic amino acid to an aromatic amino acid positioned within its hydrophobic core.

11. The bioelectronic device of claim 1 , wherein the at least one adaptor polypeptide comprises a C-terminal and/or N-terminal cysteine residue.

12. The bioelectronic device of claim 1 , wherein the at least one adaptor polypeptide is directly coupled to at least one of the first and second electrodes.

13. The bioelectronic device of claim 1 , wherein the at least one adaptor polypeptide is coupled to at least one of the first and second electrodes via a linker.

14. The bioelectronic device of claim 1 , wherein the linker is selected from the group consisting of a biotin-streptavidin linker, a spytag-spycatcher linker, a halotag linker, a thiolated linker, a thiolated tetratricopeptide repeat (TPR) linker, and a thiolated consensus tetratricopeptide repeat (CTPR) linker.

15. The bioelectronic device of claim 1 , wherein the at least one adaptor polypeptide is directly coupled to the protein.

16. The bioelectronic device of claim 1 , wherein the at least one adaptor polypeptide is coupled to the protein electrodes via a linker.

17. The bioelectronic device of claim 1 , wherein the at least one adaptor polypeptide comprises a consensus tetratricopeptide repeat (CTPR) adaptor polypeptide.

18. The bioelectronic device of claim 17 , wherein the CTPR is selected from the group consisting of CTPR1, CTPR2, CTPR3, CTPR4, CTPR5, CTPR6, CTPR7, CTPR8, CTPR9, CTPR10, CTPR11, CTPR12, CTPR13, CTPR14, CTPR15, CTPR16, CTPR17, CTPR18, CTPR19, CTPR20, and any derivatives or variants thereof.

19. The bioelectronic device of claim 1 , wherein the device comprises two CTPR adaptor polypeptides, and wherein the two CTPR adaptor polypeptides are the same size.

20. The bioelectronic device of claim 1 , wherein the device comprises two CTPR adaptor polypeptides, and wherein each CTPR adaptor polypeptide is a different size.

21. The bioelectronic device of claim 1 , wherein presence of the adaptor polypeptide reduces conductance decay as the gap between the first and second electrodes increases.

22. The bioelectronic device of claim 1 , wherein the protein is selected from the group consisting of a polymerase, a nuclease, a proteasome, a glycopeptidase, a glycosidase, a kinase and an endonuclease.

23. The bioelectronic device of claim 1 , wherein the linker and/or the at least one adaptor polypeptide is coupled to an inactive region of the protein.

24. The bioelectronic device of claim 1 , wherein the protein and the first and second electrodes are biotinylated, and wherein the linker comprises a streptavidin molecule comprising at least two biotin binding sites.

25. The bioelectronic device of claim 1 , wherein the linker comprises a distinctive negative charge.

26. The bioelectronic device of claim 25 , wherein the distinctive negative charge is conferred by addition of a glutamate moiety, an aspartate moiety, or a combination thereof, coupled to the linker.

27. The bioelectronic device of claim 25 , wherein the distinctive negative charge increases conductance through the protein.

28. The bioelectronic device of claim 25 , wherein the linker comprises a distinctive positive charge.

29. The bioelectronic device of claim 28 , wherein the distinctive positive charge is conferred by addition of an arginine moiety, a histidine moiety, a lysine moiety, or a combination thereof, coupled to the linker.

30. The bioelectronic device of claim 28 , wherein the distinctive positive charge increases or decreases conductance through the protein.

31. The bioelectronic device of claim 1 , wherein the first and/or the second electrode comprises gold, palladium, platinum, silver, copper, or any alloys thereof.

32. The bioelectronic device of claim 1 , wherein the device comprises a dielectric layer at least partially covering a surface of the first and/or second electrode.

33. The bioelectronic device of claim 1 , wherein the first electrode and second electrode are positioned so that about a 1 nm to about a 50 nm gap is formed between the two electrodes.

34. A method for direct electrical measurement of protein activity, the method comprising:

(a) introducing an analyte capable of interacting with the protein of the bioelectronic device of claim 1 ;

(b) applying a voltage bias between the first and second electrodes that is 100 mV or less; and

(c) observing fluctuations in current between the first and second electrodes that occur when the analyte interacts with the protein.

35. The method of claim 34 , wherein the analyte is a biopolymer selected from the group consisting of a DNA molecule, an RNA molecule, a peptide, a polypeptide, and a glycan.

Assignments (2)
CONFIRMATORY LICENSE Recorded Dec 5, 2023
From: ARIZONA STATE UNIVERSITY-TEMPE CAMPUS
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 065775/0535 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 15, 2022
From: LINDSAY, STUART
To: ARIZONA BOARD OF REGENTS ON BEHALF OF ARIZONA STATE UNIVERSITY
Reel/Frame 059018/0615 →
Continuity (3)
Provisional Application 63125674 · Dec 15, 2020
Provisional Application 63032266 · May 29, 2020
Related Publication 20210372986A1 · Dec 2, 2021
References Cited (218)
US 5198543A · Blanco · 1993 [cited by applicant]
US 6824974B2 · Pisharody et al. · 2004 [cited by applicant]
US 7632671B2 · Tong · 2009 [cited by applicant]
US 8628649B2 · Lindsay et al. · 2014 [cited by applicant]
US 8961757B2 · Nuckolls et al. · 2015 [cited by applicant]
US 8968540B2 · Reinhart et al. · 2015 [cited by applicant]
US 9140682B2 · Lindsay et al. · 2015 [cited by applicant]
US 9274430B2 · Gyarfas et al. · 2016 [cited by applicant]
US 9376713B2 · Bashir et al. · 2016 [cited by applicant]
US 9593372B2 · Lindsay et al. · 2017 [cited by applicant]
US 9938586B2 · Liang et al. · 2018 [cited by applicant]
US 10047392B2 · Ivankin et al. · 2018 [cited by applicant]
US 10051722B2 · Jin et al. · 2018 [cited by applicant]
US 10227694B2 · Jin et al. · 2019 [cited by applicant]
US 10378103B2 · Jin et al. · 2019 [cited by applicant]
US 10379102B2 · Lindsay et al. · 2019 [cited by applicant]
US 10422787B2 · Lindsay et al. · 2019 [cited by applicant]
US 10508296B2 · Merriman et al. · 2019 [cited by applicant]
US 10526696B2 · Jin et al. · 2020 [cited by applicant]
US 10584410B2 · Jin et al. · 2020 [cited by applicant]
US 10597767B2 · Merriman et al. · 2020 [cited by applicant]
US 10648941B2 · Merriman et al. · 2020 [cited by applicant]
US 10712334B2 · Choi et al. · 2020 [cited by applicant]
US 10737263B2 · Choi et al. · 2020 [cited by applicant]
US 10913966B2 · Merriman et al. · 2021 [cited by applicant]
US 20030124572A1 · Umek et al. · 2003 [cited by applicant]
US 20040146863A1 · Pisharody et al. · 2004 [cited by applicant]
US 20040249124A1 · Caruso et al. · 2004 [cited by applicant]
US 20050285275A1 · Son et al. · 2005 [cited by applicant]
US 20090215156A1 · Chung et al. · 2009 [cited by applicant]
US 20090226899A1 · Chen · 2009 [cited by applicant]
US 20100084276A1 · Lindsay · 2010 [cited by applicant]
US 20100184062A1 · Steinmuller-Nethl et al. · 2010 [cited by applicant]
US 20100206731A1 · Lau et al. · 2010 [cited by applicant]
US 20100285514A1 · Claussen et al. · 2010 [cited by applicant]
US 20110098218A1 · Han et al. · 2011 [cited by applicant]
US 20110312529A1 · He et al. · 2011 [cited by applicant]
US 20120228386A1 · Wu et al. · 2012 [cited by applicant]
US 20130302901A1 · Lindsay et al. · 2013 [cited by applicant]
US 20140141525A1 · Albert et al. · 2014 [cited by applicant]
US 20150010935A1 · Lindsay et al. · 2015 [cited by applicant]
US 20150017655A1 · Huang et al. · 2015 [cited by applicant]
US 20150086994A1 · Williams et al. · 2015 [cited by applicant]
US 20150142327A1 · Ashcroft et al. · 2015 [cited by applicant]
US 20150144506A1 · Lindsay et al. · 2015 [cited by applicant]
US 20150285818A1 · Banala et al. · 2015 [cited by applicant]
US 20160018384A1 · Lindsay et al. · 2016 [cited by applicant]
US 20160025702A1 · Lindsay et al. · 2016 [cited by applicant]
US 20160083789A1 · Turner et al. · 2016 [cited by applicant]
US 20160097759A1 · Lindsay et al. · 2016 [cited by applicant]
US 20160108002A1 · Zhang et al. · 2016 [cited by applicant]
US 20160146828A1 · Lindsay et al. · 2016 [cited by applicant]
US 20160177383A1 · Ashcroft et al. · 2016 [cited by applicant]
US 20160194698A1 · Lindsay · 2016 [cited by applicant]
US 20160258925A1 · Gyarfas et al. · 2016 [cited by applicant]
US 20160280723A1 · Zhang et al. · 2016 [cited by applicant]
US 20160282295A1 · Wang et al. · 2016 [cited by applicant]
US 20160319343A1 · Korlach et al. · 2016 [cited by applicant]
US 20170003245A1 · Lindsay et al. · 2017 [cited by applicant]
US 20170016852A1 · Lindsay et al. · 2017 [cited by applicant]
US 20170037462A1 · Turner et al. · 2017 [cited by applicant]
US 20170038333A1 · Turner et al. · 2017 [cited by applicant]
US 20170038369A1 · Lindsay et al. · 2017 [cited by applicant]
US 20170044605A1 · Merriman et al. · 2017 [cited by applicant]
US 20170067902A1 · Zhang et al. · 2017 [cited by applicant]
US 20170137389A1 · Zhang et al. · 2017 [cited by applicant]
US 20170168039A1 · Lindsay et al. · 2017 [cited by applicant]
US 20170276678A1 · Ervin · 2017 [cited by applicant]
US 20180031549A1 · Chen et al. · 2018 [cited by applicant]
US 20180073071A1 · Ju et al. · 2018 [cited by applicant]
US 20180095081A1 · Albert et al. · 2018 [cited by applicant]
US 20180120286A1 · Lindsay et al. · 2018 [cited by applicant]
US 20180155773A1 · Gunderson et al. · 2018 [cited by applicant]
US 20180180567A1 · Li et al. · 2018 [cited by applicant]
US 20180305727A1 · Merriman et al. · 2018 [cited by applicant]
US 20180340220A1 · Merriman et al. · 2018 [cited by applicant]
US 20190004003A1 · Merriman et al. · 2019 [cited by applicant]
US 20190041355A1 · Merriman et al. · 2019 [cited by applicant]
US 20190094175A1 · Merriman et al. · 2019 [cited by applicant]
US 20190112643A1 · Aran et al. · 2019 [cited by applicant]
US 20190234902A1 · Lima, Jr. et al. · 2019 [cited by applicant]
US 20190309008A1 · Ju et al. · 2019 [cited by applicant]
US 20190317040A1 · Lindsay et al. · 2019 [cited by applicant]
US 20190330695A1 · Guo et al. · 2019 [cited by applicant]
US 20190376135A1 · Mandell et al. · 2019 [cited by applicant]
US 20200157595A1 · Merriman et al. · 2020 [cited by applicant]
US 20210114025A1 · De Freitas Dias et al. · 2021 [cited by applicant]
US 20210208127A1 · Lindsay et al. · 2021 [cited by applicant]
US 20220252542A1 · Merriman et al. · 2022 [cited by applicant]
CN 104359946 · 2015 [cited by applicant]
JP 2016188794A · 2016 [cited by applicant]
WO WO2013038272 · 2013 [cited by applicant]
WO WO2013154999 · 2013 [cited by applicant]
WO WO2014074727 · 2014 [cited by applicant]
WO WO2015130781 · 2015 [cited by applicant]
WO WO2015131073 · 2015 [cited by applicant]
WO WO2015161119 · 2015 [cited by applicant]
WO WO2015170784 · 2015 [cited by applicant]
WO WO2016100635 · 2016 [cited by applicant]
WO WO2016161402 · 2016 [cited by applicant]
WO WO2016210386 · 2016 [cited by applicant]
WO WO2017084998 · 2017 [cited by applicant]
WO WO2017123416 · 2017 [cited by applicant]
WO WO2017189930 · 2017 [cited by applicant]
WO WO2018026855 · 2018 [cited by applicant]
WO WO2018132457 · 2018 [cited by applicant]
WO WO2018200687 · 2018 [cited by applicant]
WO WO2018208505 · 2018 [cited by applicant]
WO WO2019046589 · 2019 [cited by applicant]
WO WO2019086305 · 2019 [cited by applicant]
WO WO2019211622 · 2019 [cited by applicant]
WO WO2019217600 · 2019 [cited by applicant]
WO WO2019222527 · 2019 [cited by applicant]
WO WO2020160300 · 2020 [cited by applicant]
WO WO2020243207 · 2020 [cited by applicant]
WO WO2020257654 · 2020 [cited by applicant]
WO WO2021163275 · 2021 [cited by applicant]
WO WO2021173681 · 2021 [cited by applicant]
WO WO2021222791 · 2021 [cited by applicant]
Lindsay. Ubiquitous Electron Transport in Non-Electron Transfer Proteins. Life (Basel). May 20, 2020;10(5):72. 13 pages. [cited by applicant]
Main et al., Design of stable alpha-helical arrays from an idealized TPR motif. Structure. May 2003;11(5):497-508. [cited by applicant]
Mejias et al., Controlled nanometric fibers of self-assembled designed protein scaffolds. Nanoscale. Oct. 7, 2014;6(19):10982-8. [cited by applicant]
Sek et al., Conductance of alpha-helical peptides trapped within molecular junctions. J Phys Chem B. Oct. 5, 2006;110(39):19671-7. [cited by applicant]
Zhang et al., Role of contacts in long-range protein conductance. Proc Natl Acad Sci U S A. Mar. 26, 2019;116(13):5886-5891. [cited by applicant]
Zhang et al., Observation of Giant Conductance Fluctuations in a Protein. Nano Futures. 2017;1(3):035002. 25 pages. [cited by applicant]
International Search Report and Written Opinion for PCT/US21/34698. Mailed Sep. 30, 2021. 10 pages. [cited by applicant]
Altschul et al., Basic local alignment search tool. J Mol Biol. Oct. 5, 1990;215(3):403-10. [cited by applicant]
Altschul et al., Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res. Sep. 1, 1997;25(17):3389-402. [cited by applicant]
Kyte et al., A simple method for displaying the hydropathic character of a protein. J Mol Biol. May 5, 1982;157(1):105-32. [cited by applicant]
Pearson. Using the FASTA program to search protein and DNA sequence databases. Methods Mol Biol. 1994;24:307-31. [cited by applicant]
Zhang et al., Engineering an Enzyme for Direct Electrical Monitoring of Activity. ACS Nano. Feb. 25, 2020;14(2):1360-1368. [cited by applicant]
Zhang et al., Electronic Conductance Resonance in Non-Redox-Active Proteins. J Am Chem Soc. Apr. 1, 2020;142(13):6432-6438. [cited by applicant]
Zhang et al., Electronic Decay Length in a Protein Molecule. Nano Lett. Jun. 12, 2019;19(6):4017-4022. [cited by applicant]
Ackerman et al., Massively multiplexed nucleic acid detection with Cas13. Nature. Jun. 2020;582(7811):277-282. [cited by applicant]
Adhikari et al., Conductivity of individual Geobacter pili. RSC Advances, 2016. 6: p. 8354-8357. [cited by applicant]
Alloway et al., Interface Dipoles Arising from Self-Assembled Monolayers on Gold: UV-Photoemission Studies of Alkanethiols and Partially Fluorinated Alkanethiols. J. Phys. Chem. B 2003, 107:11690-11699. [cited by applicant]
Amdursky et al., Electronic transport via proteins. Adv Mater. Nov. 12, 2014;26(42):7142-61. [cited by applicant]
Amdursky et al., Solid-state electron transport via cytochrome c depends on electronic coupling to electrodes and across the protein. PNAS, Apr. 15, 2014, vol. 111, No. 15, pp. 5556-5561. [cited by applicant]
Anzai et al., Avidin-biotin complexation for enzyme sensor Applications, Trends in Analytical Chemistry, 1994, 13(5): 205-210. [cited by applicant]
Artes et al., Transistor-like Behavior of Single Metalloprotein Junctions. Nano Lett.,2012, 12(6), pp. 2679-2684 (publication date (Web): Oct. 5, 2011). [cited by applicant]
Aubert et al., Intraprotein radical transfer during photoactivation of DNA photolyase. Nature. Jun. 1, 2000;405(6786):586-90. [cited by applicant]
Ausubel et al. Current Protocols in Molecular Biology, John Wiley & Sons, New York, 1998. 19 pages. [cited by applicant]
Barhoumi et al., Urease immobilization on biotinylated polypyrrole coated ChemFEC devices for urea biosensor development, IRBM, Apr. 1, 2008, 29(2-3): 192-201. [cited by applicant]
Bayer et al., 3-(N-Maleimido-propionyl) Biocytin: A Versatile Thiol-Specific Biotinylating Reagent, Analytical Biochemistry, 1985, 149: 529-536. [cited by applicant]
Bostick et al., Protein bioelectronics: a review of what we do and do not know. Rep Prog Phys. Feb. 2018;81(2):026601. 58 pages. [cited by applicant]
Carter et al., Functional protein materials: beyond elastomeric and structural proteins, Polym. Chem. 2019, 10:2952-2959. [cited by applicant]
Castellarnau et al., Integrated microanalytical system based on electrochemical detection and cell positioning, Materials Science and Engineering, 2006, 26: 405-410. [cited by applicant]
Chang et al., Chemical recognition and binding kinetics in a functionalized tunnel junction. Nanotechnology. Jun. 15, 2012;23(23):235101. 28 pages. [cited by applicant]
Chen et al., DNA sequencing using electrical conductance measurements of a DNA polymerase, Nature Nanotechnology, May 5, 2013, pp. 1-7; https://doi.org/10.1038/nnano.2013.71. 7 pages. [cited by applicant]
Chichil et al., Linkers in the structural biology of protein-protein interactions. Protein Sci. Feb. 2013;22(2):153-67. [cited by applicant]
Chin et al., Addition of p-Azido-I-phenylalanine to the Genetic Code of [cited by applicant]
Choi et al. Site-specific inhibition of integrin alpha v beta 3-vitronectin association by a serasp-val sequence through an Arg-Gly-Asp-binding site of the integrin, Proteomics, vol. 10, Issue 1, No. 1 Jan. 2010, pp. 72… [cited by applicant]
Choi et al., Single-Molecule Lysozyme Dynamics Monitored by an Electronic Circuit, Science (2012) 335:319-324. [cited by applicant]
Cui et al., Layer-by-layer 1 assembly of multilayer filme composed of avidin and biotin-labeled antibody for immunosensing, Biosensors And Bioelectronics, Jan. 1, 2003, 18(1): 59-67. [cited by applicant]
Cui et al., Reproducible measurement of single-molecule conductivity. Science. Oct. 19, 2001;294(5542):571-4. [cited by applicant]
Dellafiore et al., Modified Nucleoside Triphosphates for In-vitro Selection Techniques. Front Chem. May 4, 2016;4:18. [cited by applicant]
Dissertation by Joshua Sadar, Top-Down and Bottom-Up Strategies to Prepare Nanogap Sensors for Controlling and Characterizing Single Biomolecules, Jul. 2019, 160 pages. [cited by applicant]
Duffy et al., Modified nucleic acids: replication, evolution, and next-generation therapeutics. BMC Biology, Sep. 2, 2020. 18:112. 14 pages. [cited by applicant]
Fairhead et al., Plug-and-play pairing via defined divalent streptavidins. J Mol Biol. Jan. 9, 2014;426(1):199-214. [cited by applicant]
Fujino et al, Chimeric RNA Oligonucleotides Incorporating Triazole-Linked Trinucleotides: Synthesis and Function as mRNA in Cell-Free Translation Reactions. J Org Chem. Oct. 7, 2016;81(19):8967-8976. [cited by applicant]
Fulton et al., Purification of monoclonal antibody against Ebola GP1 protein expressed in Nicotiana benthamiana. J Chromatogr A. Apr. 10, 2015;1389:128-32. [cited by applicant]
Garg et al., Interface Electrostatics Dictates the Electron Transport via Bioelectronic Junctions. ACS Appl Mater Interfaces. Dec. 5, 2018;10(48):41599-41607. [cited by applicant]
Gerrits et al., Cell-Free Synthesis of Defined Protein Conjugates by Sitedirected Cotranslational Labeling, NCBI Bookshelf. Jan. 1, 2013, Retrieved from the Internet: URL:https://ww.ncbi.nlm.nih.gov/books/NBK6497. [cited by applicant]
Giese et al., Direct observation of hole transfer through DNA by hopping between adenine bases and by tunnelling. Nature. Jul. 19, 2001;412(6844):318-20. [cited by applicant]
Giese et al., Long distance charge transport through DNA: quantification and extension of the hopping model. Chemphyschem. Dec. 15, 2000;1(4):195-8. [cited by applicant]
Gonnet et al., Exhaustive matching of the entire protein sequence database. Science. Jun. 5, 1992;256(5062):1443-5. [cited by applicant]
Guo et al., Tuning electronic transport via hepta-alanine peptides junction by tryptophan doping. Proc Natl Acad Sci U S A. Sep. 27, 2016;113(39):10785-90. [cited by applicant]
Hajian et al., Detection of unamplified target genes via CRISPR-Cas9 immobilized on a graphene field-effect transistor. Nat Biomed Eng. Jun. 2019;3(6):427-437. [cited by applicant]
Harriman. Further comments on the redox potentials of tryptophan and tyrosine. Journal of Physical Chemistry 1987. 91:6102-6104. [cited by applicant]
Hays et al., Development of capacitance based immunosensors on mixed self-assembled monolayers. Sensors and Actuators B: Chemical, Apr. 26, 2006, 114(2): 1064-1070. [cited by applicant]
Hohl et al. Engineering a Polyspecific Pyrrolysyl-tRNA Synthetase by a High Throughput FACS Screen. Sci Rep. Aug. 19, 2019;9(1):11971. [cited by applicant]
Hozel et al., Trapping Single Molecules by Dielectrophoresis, Physical Review Letters, 2005, 128102-1-4. [cited by applicant]
Ihalainene et al., Application of paper-supported printed gold eletrodes for impedimetric immunosensor development, Biosensors 2013, 3:1-17. [cited by applicant]
Jeffrey, An Introduction to Hydrogen Bonding. Oxford University Press New York. 1997. TOC only. 6 pages. [cited by applicant]
Kluenker et al., Monitoring Thiol-Ligand exchange on Au nanoparticle surfaces. Langmuir. Jan. 30, 2018;34(4):1700-1710. [cited by applicant]
Kotlowski, Fine discrimination of volatile compounds by graphene-immobilized odorant-binding proteins, Sensors and Actuatores B: Chemical 2018 (256): 564-72. [cited by applicant]
Krishnan et al., Long-Range Conductivity in Proteins Mediated by Aromatic Residues, ACS Phys. Chem Au 2023, 3:444-455. [cited by applicant]
Lagunas et al., Long distance electron transfer through the aqueous solution between redox partner proteins. Nat Commun. Dec. 4, 2018;9(1):5157. [cited by applicant]
Lai et al., Monoclonal antibody produced in plants efficiently treats West Nile virus infection in mice. Proc Natl Acad Sci U S A. Feb. 9, 2010;107(6):2419-24. [cited by applicant]
Lai et al., Robust production of virus-like particles and monoclonal antibodies with geminiviral replicon vectors in lettuce. Plant Biotechnol J. Jan. 2012;10(1):95-104. [cited by applicant]
Leary et al., Unambiguous one-molecule conductance measurements under ambient conditions. Nano Lett. Jun. 8, 2011;11(6):2236-41. [cited by applicant]
Li et al., CRISPR-SE: a brute force search engine for CRISPR design. NAR Genom Bioinform. Feb. 23, 2021;3(1):lqab013. [cited by applicant]
Lindsay et al., Recognition tunneling, Nanotechnology 2010, 21:262001, 12 pp. [cited by applicant]
Liu et al., Vertical T cellimmunodomincance and epitope entropy determine HIV-1 escape. J Clin Invest. Jan. 2013; 123(1):380-93. [cited by applicant]
Maalouf R. et al., Label-Free Detection of Bacteria by Electrochemical Impedance Spectroscopy: Comparison to Surface Plasmon Resonance. Anal. Chem, May 25, 2007, vol. 79, No. 13, pp. 4879-4886. [cited by applicant]
Malvankar et al., Tunable metallic-like conductivity in microbial nanowire networks. Nat Nanotechnol. Aug. 7, 2011;6(9):573-9. [cited by applicant]
Marakova et al., An updated evolutionary classification of CRISPR-Cas systems. Nat Rev Microbiol. Nov. 2015;13(11):722-36. [cited by applicant]
Mckenzie et al., Recent progress in non-native nucleic acid modifications. Chem Soc Rev. Apr. 26, 2021;50(8):5126-5164. [cited by applicant]
Metsky et al., Diagnostic design with machine learning model-based optimization. bioRxiv 2020.11.28.401877: 95 pages. [cited by applicant]
Mullegama et al., Nucleic Acid Extraction from Human Biological Samples. Methods Mol Biol 2019;1897:359-383. [cited by applicant]
Nitzan. Chemical dynamics in condensed phases. Oxford University Press., Oxford. 2006. TOC only. 13 pages. [cited by applicant]
Odella et al., Controlling Proton-Coupled Electron Transfer in Bioinspired Artificial Photosynthetic Relays. J Am Chem Soc. Nov. 14, 2018;140(45):15450-15460. [cited by applicant]
Olsen et al., Electronic Measurements of Single-Molecule Processing by DNA Polymerase I (Klenow Fragment), Journal of the American Chemical Society (Apr. 30, 2013); pp. 1-12; DOI: 10.1021/ja311603r. [cited by applicant]
Ouerghi et al., Impedimetric immunosensor using avidin-biotin for antibody immobilization, Bioelectrochemistry, May 15, 2002, 56(1-2): 131-133. [cited by applicant]
Pang et al. Fixed-Gap Tunnel Junction for Reading DNA Nucleotides, ACS Nano, 2014, 8(12), pp. 11994-12003 (Publication Date (Web): Nov. 7, 2014). [cited by applicant]
Prodromidis et al., Impedimetric immunosensors—A review, Electrochimica Acta, May 30, 2010, 55(14): 4227-4233. [cited by applicant]
Quast et al., Cotranslational incorporation of non-standard amino acids using cell-free protein synthesis. FEBS Lett. Jul. 8, 2015;589(15):1703-12. [cited by applicant]
Ruiz et al., Bioengineering a Single-Protein Junction. J Am Chem Soc. Nov. 1, 2017;139(43):15337-15346. [cited by applicant]
Sambrook et al., Molecular Cloning: A Laboratory Manual, 3d ed., Cold Spring Harbor Press, 2001. TOC only. 23 pages. [cited by applicant]
Sano et al., Cooperative biotin binding by streptavidin. Electrophoretic behavior and subunit association of streptavidin in the presence of 6 M urea. J Biol Chem. Feb. 25, 1990;265(6):3369-73. [cited by applicant]
Seifert, Characterization of Streptavidin Binding to Biotinylated, Binary Self-Assembled Thio Monolayers—Influence of Component Ratio and Solvent, Langmuir, 2010, 26(9): 6386-93. [cited by applicant]
Sela-Culang et al., The strutural basis of antibody-antigen recognition, Frontiers in Immunology, 2013, vol. 4, 13 pages. [cited by applicant]
Sequences of amino acids as found on the world wide web at bmrb.wisc.edu/referenc/choufas. 4 pages. [cited by applicant]
Shimura & Yoshida, Heterogeneous photocatalytic hydrogen production from water and biomass derivatives, Energy Environmental Science 2011, 4: 2467. [cited by applicant]
Smith. The hydrophilic nature of a clean gold surface. J. Colloid Interface Science 1980. 75:51-55. [cited by applicant]
Staals et al., RNA targeting by the type III-A CRISPR-Cas Csm complex of Thermus thermophilus. Mol Cell. Nov. 20, 2014;56(4):518-30. [cited by applicant]
Tripkovic et al., Standard hydrogen electrode and potential of zero charge in density functional calculations. Phys. Rev. B 2011. 84:115452. [cited by applicant]
Tuchband et al., Insulated gold scanning tunneling microscopy probes for recognition tunneling in an aqueous environment. Rev Sci Instrum. Jan. 2012;83(1):015102. [cited by applicant]
Uygun et al., CRISPR-dCAS9 powered impedimetric biosensor for label-free detection of circulating tumor DNAs, Analytica Chimica Acta 2020, 1121:35-41. [cited by applicant]
Vaish et al., A novel, modification-dependent ATP-binding aptamer selected from an RNA library incorporating a cationic functionality. Biochemistry. Jul. 29, 2003;42(29):8842-51. [cited by applicant]
Varga et al., Binding of a Mouse Monoclonal IgE (anti-DNP) antibody to radio-derivatized polystyrene-DNP complexes, The FASEB Journal, Federation of American Societies for Experimental Biology, Jun. 1, 1990, 4(9): 2678-… [cited by applicant]
Vattay et al., Quantum Criticality at the Origin of Life. Journal of Physics: Conference Series 2015. 626: p. 012023. 11 pages. [cited by applicant]
Willner et al., Mediated electron transfer in glutathione reductase organized in self-assembled monolayers on Au electrodes. J. Am. Chem. Soc., 1992. 114: p. 10965-10966. [cited by applicant]
Xiao et al., Conductance titration of single-peptide molecules. J Am Chem Soc. May 5, 2004;126(17):5370-1. [cited by applicant]
Yang et al., Plant-produced Zika virus envelope protein elicits neutralizing immune responses that correlate with protective immunity against Zika virus in mice. Plant Biotechnol J. Feb. 2018; 16(2):572-580. [cited by applicant]
Yoon, Hidden Markov Models and their Applications in Biological Sequence Analysis, Current Genomics, 2009, 10:402-415. [cited by applicant]
Zhang et al., Electronic Transport in Molecular Wires of Precisely Controlled Length Built from Modular Proteins, ACS Nano 2022, 16(1): 1671-1680. [cited by applicant]
Zwolak et al. Electronic Signature of DNA Nucleotides via Transverse Transport, NanoLett., 2005, 5(3), pp. 421-424 (Publication Date (Web): Feb. 12, 2005). [cited by applicant]