IP Library › Granted Patent US 12,650,418
Granted Patent B2
US 12,650,418 · App. 18/220,521 · Granted Jun 9, 2026

Water monitoring with solid state nanopores

Inventor: Zehui Xia (Philadelphia, PA)
Assignee: Goeppert, LLC
G01N33/1813
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Quick Facts
Patent No.
US 12,650,418
App. No.
18/220,521
Granted
Jun 9, 2026
Kind
B2
Abstract

A solid-state nanopore system includes a single-molecule chip that works on the principle of pore occlusion by the detected molecule, which then can be registered as a change in ionic current. Low-noise and low-capacitance glass chips are used with ultrathin (<20 nm) silicon nitride (SiN) nanopores of 1.5-5 nm diameter and a miniaturized nanopore reader are used as the nanopore sensor, which is capable of sensing the presence of mercury ion (Hg 2+ ) and lead ion (Pb 2+ ) at concentrations down to 0.5 nM and 5 nM, respectively. Detectable distinct electrical translocation characteristics between the two metal ions were enabled by short DNA molecules (aptamers) functioning as a carrier, binding via specific interactions with the metal ions to provide a selective nanopore sensor for water monitoring by identification of electrical fingerprints of the respective ions.

Claims (23)

1 . A method of sensing a lead ion in a fluid, comprising:

inserting a solid-state nanopore chip having at least one nanopore of less than 20 nm diameter into a fluidic cell;

providing a fluid into the fluidic cell including a guanine (G) rich aptamer that binds with lead ions in the fluid to form lead stabilized G-quadruplex cages; and

electronically detecting and measuring concentration of the lead stabilized G-quadruplex cages as the fluid passes through the at least one nanopore of the solid-state nanopore chip.

2 . The method of claim 1 , wherein the solid-state nanopore chip comprises silicon nitride (SiN) nanopores that are less than 20 nm thick and have a diameter of 1.5-5 nm.

3 . The method of claim 1 , wherein the lead ion has a concentration of 5 nM in the fluid.

4 . A method of sensing a mercury ion in a fluid, comprising:

inserting a solid-state nanopore chip having at least one nanopore of less than 20 nm diameter into a fluidic cell;

providing a fluid into the fluidic cell including a thymine (T) rich aptamer that binds with mercury ions in the fluid to form a T-Hg-T base pairs in a duplex hairpin structure; and

electronically detecting and measuring concentration of the T-Hg-T base pairs in the duplex hairpin structure as the fluid passes through the at least one nanopore of the solid-state nanopore chip.

5 . The method of claim 4 , wherein the mercury ion has a concentration of 0.5 nM in the fluid.

6 . The method of claim 1 , wherein electronically detecting and measuring the concentration of the lead stabilized G-quadruplex cages comprises recording translocation events of lead stabilized G-quadruplex cages one at a time using a nanopore reader as the lead stabilized G-quadruplex cages translocate through the at least one nanopore.

7 . The method of claim 1 , wherein the fluid is spacecraft water.

8 . A water monitoring system adapted to sense at least one of lead or mercury ions in water, comprising:

a fluidic cell that holds water comprising a concentration of an at least one of a guanine (G) rich aptamer configured to bind with lead ions in the fluid to form lead stabilized G-quadruplex cages or a thymine (T) rich aptamer configured to bind with mercury ions in the fluid to form a T-Hg-T base pairs in a duplex hairpin structure;

a solid-state nanopore chip having at least one nanopore of less than 20 nm diameter disposed in the fluidic cell for testing the water; and

a nanopore reader configured to detect and measure concentration of at least one of the lead stabilized G-quadruplex cages or the T-Hg-T base pairs in the duplex hairpin structure the carrier as the water passes through the at least one nanopore of the solid-state nanopore chip.

9 . The water monitoring system of claim 8 , wherein the fluidic cell is disposed on a spacecraft.

10 . The water monitoring system of claim 8 , wherein the solid-state nanopore chip comprises silicon nitride (SiN) nanopores that are less than 20 nm thick and have a diameter of 1.5-5 nm.

11 . The water monitoring system of claim 8 , wherein the nanopore reader records translocation events of at least one of lead stabilized G-quadruplex cages or T-Hg-T base pairs in the duplex hairpin structure one at a time as the at least one of lead stabilized G-quadruplex cages or T-Hg-T base pairs in the duplex hairpin structure translocate through the at least one nanopore.

12 . The method of claim 4 , wherein the solid-state nanopore chip comprises silicon nitride (SiN) nanopores that are less than 20 nm thick and have a diameter of 1.5-5 nm.

13 . The method of claim 4 , wherein electronically detecting and measuring the concentration of the T-Hg-T base pairs in the duplex hairpin structure comprises recording translocation events of T-Hg-T base pairs in the duplex hairpin structure one at a time using a nanopore reader as the T-Hg-T base pairs in the duplex hairpin structure translocate through the at least one nanopore.

14 . The method of claim 4 , wherein the fluid is spacecraft water.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 11, 2023
From: XIA, ZEHUI
To: GOEPPERT, LLC
Reel/Frame 064214/0784 →
Continuity (1)
Related Publication 20250020623A1 · Jan 16, 2025
References Cited (78)
US 11598012B2 · Voskian · 2023 [cited by examiner]
US 20180275088A1 · Huff · 2018 [cited by examiner]
CN 105087791A · 2015 [cited by examiner]
EP 4177606A1 · 2023 [cited by examiner]
JP 2004294422A · 2004 [cited by examiner]
Wen et al., “A Sensitive and Label-Free Pb(II) Fluorescence Sensor Based on a DNAzyme Controlled G-Quadruplex/Thioflavin T Conformation”, Dec. 16, 2016, Sensors, 16, 2155. (Year: 2016). [cited by examiner]
Straub, John E., II, et al., “International Space Station Portable Water Characterization for 2013”, 44th International Conference on Environmental Systems, Tucson, Arizona, Jul. 13-17, 2014. [cited by applicant]
Surwade, Sumedh P., et al., “Water Desalination Using Nanoporous Single-Layer Graphene”, Nature Nanotechnology, vol. 10, Issue 5, May 2015, (online: Mar. 23, 2015), pp. 459-464. [cited by applicant]
The Nanopore Site, https://www.thenanoporesite.com/nanopore-companies, printed on Oct. 3, 2025. [cited by applicant]
Thiruraman, Jothi Priyanka, et al., “Ions and Water Dancing Through Atom-Scale Holes: A Perspective Toward “Size Zero””, ACS Nano, vol. 14, Issue 4, Mar. 20, 2020, pp. 3736-3746. [cited by applicant]
Thiruraman, Jothi Priyanka, et al., “Stochastic lonic Transport in Single Atomic Zero-Dimensional Pores”, ACS Nano, vol. 14 Issue 9, Aug. 11, 2020, pp. 11831-11845. [cited by applicant]
Uram, Jeffrey D., et al., “Submicrometer Pore-Based Characterization and Quantification of Antibody-Virus Interactions”, Nano Micro Small, vol. 2, No. 8-9, Aug. 2006, pp. 967-972. [cited by applicant]
Venta, Kimberly, et al., “Differentiation of Short, Single-Stranded DNA Homopolymers in Solid-State Nanopores”, ACS Nano, vol. 7, Issue 5, Apr. 26, 2013, pp. 4629.4636. [cited by applicant]
Wang, Guihua, et al., “Nanopore Detection of Copper Ions Using a Polyhistidine Probe”, Biosensors and Bioelectronics, vol. 53, Mar. 15, 2014, pp. 453.458. [cited by applicant]
Wang, Guihua, et al., “Probing Mercury (II)—DNA Interactions by Nanopore Stochastic Sensing”, The Journal of Physical Chemistry B, vol. 117, Issue 17, Apr. 8, 2013, pp. 4763-4769. [cited by applicant]
Wanunu, Meni, “Nanopores: A Journey Towards DNA Sequencing”, Physics of Life Reviews, vol. 9, Issue 2, Jun. 2012, pp. 125-158. [cited by applicant]
Wanunu, Meni, et al., “Discrimination of Methylcytosine from Hydroxymethylcytosine in DNA Molecules”, Journal of the American Chemical Society, vol. 133, Issue 3, Jan. 26, 2011 (online: Dec. 14, 2010), pp. 486-492. [cited by applicant]
Wanunu, Meni, et al., “Nanopore Analysis of Individual RNA/Antibiotic Complexes”, ACS Nano, vol. 5, No. 12, Nov. 8, 2011, pp. 9345-9353. [cited by applicant]
Wanunu, Meni, et al., “Rapid Electronic Detection of Probe-Specific microRNAs Using Thin Nanopore Sensors”, Nature Nanotechnology, vol. 5, No. 11, Nov. 2010 (online: Oct. 24, 2010), pp. 807-814. [cited by applicant]
Wei, Ruoshan, et al., “Stochastic Sensing of Proteins with Receptor-Modified Solid-State Nanopores”, Nature Nanotechnology, vol. 7, No. 4, Apr. 2012 (online: Mar. 11, 2012). pp. 257-263. [cited by applicant]
Wen, Shuang, et al., “Highly Sensitive and Selective DNA-Based Detection of Mercury(II) with a-Hemolysin Nanopore”, Journal of the American Chemical Society, vol. 133, Issue 45, Oct. 13, 2011, pp. 18312-18317. [cited by applicant]
Wu, Yuangen, et al., “Selection of a DNA Aptamer for Cadmium Detection Based on Cationic Polymer Mediated Aggregation of Gold Nanoparticles”, Analyst, vol. 139, Issue 6, Mar. 21, 2014 (online: Dec. 16, 2013), pp. 1550-1… [cited by applicant]
Xia, Zehui, et al., “Deoxyribonucleic Acid Extraction from Mars Analog Soils and Their Characterization with Solid-State Nanopores”, Astrobiology, vol. 22, No. 8, Aug. 2022 (online: Jul. 25, 2022), pp. 992-1008. [cited by applicant]
Xia, Zehui, et al., “New-Generation Spacecraft Water Monitoring With Flight-Ready Solid State Nanopores”, 51st International Conference on Environmental Systems, Jul. 10-14, 2022. [cited by applicant]
Xia, Zehui, et al., “Protein-Enabled Detection of Ibuprofen and Sulfamethoxazole Using Solid-State Nanopores”, Proteomics and Systems Biology, vol. 22, Issue 5-6, Mar. 22, 2022 (online: Jan. 2, 2022). [cited by applicant]
Xia, Zehui, et al., Spacecraft Water Analysis with Nanopore (SWAN), 53rd International Conference on Environmental Systems, Jul. 21-25, 2024. [cited by applicant]
Xue, Liang, et al., “Solid-State Nanopores Sensors”, Nature Reviews Materials, vol. 5, No., Dec. 2020 (online: Sep. 21, 2020), pp. 931-951. [cited by applicant]
Zhmud, B.V., “Influence of Chemical Pretreatment on the Surface Properties of Silicon Nitride Powder”, Colloids and Surfaces A: Physicochemical and Engineering Aspects, vol. 158, Issue 3, Nov. 1999, pp. 327-341. [cited by applicant]
Acar, Elif Turker, et al., “Biomimetic Potassium-Selective Nanopores”, Science Advances, vol. 5, Issue 2, Feb. 8, 2019. [cited by applicant]
Akeson, Mark, et al., “Microsecond Time-Scale Discrimination Among Polycytidylic Acid, Polyadenylic Acid, and Polyuridylic Acid as Homopolymers or as Segments Within Single RNA Molecules”, Biophysical Journal, vol. 77, … [cited by applicant]
Amaya-González, Sonia, et al., “Aptamer-Based Analysis: A Promising Alternative for Food Safety Control”, Sensors, vol. 13, Issue 12, Nov. 28, 2013, pp. 16292-16311. [cited by applicant]
Balan, Adrian, et al., “Improving Signal-to-Noise Performance for DNA Translocation in Solid-State Nanopores at MHz Bandwidths”, Nano Letters, vol. 14, Issue 12, Dec. 2014, pp. 7215-7220. [cited by applicant]
Balan, Adrian, et al., “Suspended Solid-State Membranes on Glass Chips with Sub 1-pF Capacitance for Biomolecule Sensing Applications”, Scientific Reports, vol. 5, Article No. 17775, Dec. 8, 2015. [cited by applicant]
Bandara, Y.M. Nuwan D.Y., et al., “Chemically Functionalizing Controlled Dielectric Breakdown Silicon Nitride Nanopores by Direct Photohydrosilylation”, ACS Applied Materials and Interfaces, vol. 11, Issue 33, Jul. 26, … [cited by applicant]
Bhattacharyya, Debmalya, et al., “Metal Cations in G-Quadruplex Folding and Stability”, Frontiers in Chemistry, vol. 4, Article 38, Sep. 9, 2016. [cited by applicant]
Bock, James J., et al., “Silicon Nitride Micromesh Bolometer Arrays for SPIE”, Proceedings of SPIE, Astronomical Telescopes and Instrumentation, Kona, HI, Jul. 31, 1998. [cited by applicant]
Branton, Daniel, et al., “The Potential and Challenges of Nanopore Sequencing”, Nature Biotechnology, vol. 26, No. 10, Oct. 2008, pp. 1146-1153. [cited by applicant]
Briggs, Kyle, et al., “Kinetics of Nanopore Fabrication During Controlled Breakdown of Dielectric Membranes in Solution”, Nanotechnology, vol. 26, Feb. 4, 2015. [cited by applicant]
Chakraborty, I., et al., “MEMS Micro-Valve for Space Applications”, Institute of Electrical Engineers of Japan, Transducers, Sendai, Japan, Jun. 7, 1999 (revised Feb. 7, 2022). [cited by applicant]
Chien, Chen-Chi, et al., “Single-Stranded DNA Translocation Recordings Through Solid-State Nanopores on Glass Chips at 10 MHz Measurement Bandwidth”, ACS Nano, vol. 13, Issue 9, Aug. 26, 2019 (web), pp. 10545-10554. [cited by applicant]
Chou, Yung-Chien, et al., “Lifetime and Stability of Silicon Nitride Nanopores and Nanopore Arrays for Ionic Measurements”, ACS Nano, vol. 14, Issue 6, Apr. 10, 2020, pp. 6715-6728. [cited by applicant]
Chuang, Wen-Hsien, et al., “Mechanical Property Characterization of LPCVD Silicon Nitride Thin Films ant Cryogenic Temperatures”, Journal of MIcroelectromechanical Systems, vol. 13, No. 5, Oct. 2004, pp. 870-879. [cited by applicant]
Cohen-Tanugi, David, et al., “Water Desalination Across Nanoporous Graphene”, Nano Letters, vol. 12, Issue 7, Jun. 5, 2012, pp. 3602-3608. [cited by applicant]
Danda, Gopinath, et al., “Two-Dimensional Nanopores and Nanoporous Membranes for Ion and Molecule Transport”, Manuscript, Feb. 1, 2019. [cited by applicant]
Das, Paul Masih, et al., “Centimeter-Scale Nanoporous 2D Membranes and Ion Transport: Porous MoS2 Monolayers in a Few-Layer Matrix”, Nano Letters, vol. 19, Issue 1, Dec. 11, 2018, pp. 392-399. [cited by applicant]
Deamer, David W., et al., “Characterization of Nucleic Acids by Nanopore Analysis”, Accounts of Chemical Research, vol. 35, No. 10, Sep. 27, 2002, pp. 817-825. [cited by applicant]
Deamer, David W., et al., “Nanopores and Nucleic Acids: Prospects for Ultrarapid Sequencing”, Trends Biotechnol, vol. 18, Issue 4, Apr. 2000, pp. 147-151. [cited by applicant]
Deamer, David, et al., “Three Decades of Nanopore Sequencing”, Nature Biotechnology, vol. 34, No. 5, May 2016, pp. 518-524. [cited by applicant]
EPA, “National Primary Drinking Water Regulations”, EPA 816-F-09-004, May 2009. [cited by applicant]
Feng, Jiandong, et al., “Identification of Single Nucleotides in MoS2 Nanopores”, Nature Nanotechnology, vol. 10, No. 12, Dec. 2015 (online: Sep. 21, 2015), pp. 1070-1076. [cited by applicant]
Feng, Jiandong, et al., “Observation of Ionic Coulomb Blockade in Nanopores”, Nature Materials, vol. 15, Aug. 2016 (online: Mar. 28, 2016), pp. 850-855. [cited by applicant]
Fried, Jasper P., et al., “In Situ Solid-State Nanopore Fabrication”, Royal Society of Chemistry, vol. 50, Feb. 24, 2021, pp. 4974-4992. [cited by applicant]
Garcia, Hector D., et al., “Establishment of Exposure Guidelines for Lead in Spacecraft Drinking Water”, Aviation, Space, and Environmental Medicine, vol. 85, No. 7, Jul. 2014, pp. 715-720. [cited by applicant]
Gu, Li-Qun, et al., “Single Molecule Sensing by Nanopores and Nanopore Devices”, National Institute of Health Public Access, Author Manuscript, Dec. 23, 2010. [cited by applicant]
Jain, Tarun, et al., “Heterogeneous Sub-Continuum lonic Transport in Statistically Isolated Graphene Nanopores”, Nature Nanotechnology, vol. 10, Dec. 2015 (online: Oct. 5, 2015), pp. 1053-1057. [cited by applicant]
Kasianowicz, John J., et al., “Characterization of Individual Polynucleotide Molecules Using a Membrane Channel”, Proceedings of the National Academy of Sciences, vol. 93, No. 24, Nov. 26, 1996, pp. 13770-13773. [cited by applicant]
Kim, Mina, et al., “Arsenic Removal from Vietnamese Groundwater Using the Arsenic-Binding DNA Aptamer”, Environmental Science & Technology, vol. 43, No. 24, Nov. 12, 2009, pp. 9335-9340. [cited by applicant]
Kong, Jinglin, et al., “Specific Biosensing Using DNA Aptamers and Nanopores”, Advanced Functional Materials, vol. 29, No. 3, Jan. 17, 2019, 1807555 (6 pages). [cited by applicant]
Kwok, Harold, et al., “Nanopore Fabrication by Controlled Dielectric Breakdown”, PLOS One, vol. 9, Issue 3, Mar. 21, 2014. [cited by applicant]
Lerner, Leticia Koch, et al., “Replication of G Quadruplex DNA”, Genes, vol. 10, Issue 2, Jan. 29, 2019. [cited by applicant]
Lin, Kabin, et al., “Surface Charge Density Inside a Silicon Nitride Nanopore”, Langmuir, vol. 37, Issue 35, Aug. 4, 2021, pp. 10521-10528. [cited by applicant]
Lin, Zhenzhen, et al., “Impedimetric Immobilized DNA-Based Sensor for Simultaneous Detection of Pb2+, Ag+, and Hg2+”, Analytical Chemistry, Jul. 28, 2011, pp. 6896-6901. [cited by applicant]
Martin, Lisa C., et al., “Thin Film Sensors for Surface Measurements”, NASA/TM-2001-211149, 19th International Congress on Instrumentation in Aerospace Simulation Facilities, Cleveland, OH, Aug. 27-30, 2001. [cited by applicant]
Mayne, Laura,a et al., “The Design and Characterization of Multifunctional Aptamer Nanopore Sensors”, ACS Nano, vol. 12, Issue 5, May 2, 2018, pp. 4844-4852. [cited by applicant]
Meller, Amit, et al., “Single Molecule Measurements of DNA Transport Through a Nanopore”, Electrophoresis, vol. 23, Issue 16, Aug. 20, 2002, pp. 2583-2591. [cited by applicant]
Merchant, Christopher A., et al., “DNA Translocation Through Graphene Nanopores”, Nano Letters, vol. 10, Issue 8, Jul. 23, 2010, pp. 2915-2921. [cited by applicant]
Mikolajick, Thomas, “The Influence of Surface Oxidation on the pH-Sensing Properties of Silicon Nitride”, Sensors and Actuators B: Chemical, vol. 58, Issues 1-3, Sep. 21, 1999, pp. 450-455. [cited by applicant]
Niedzwiecki, David J., et al., “Detection of Single-Analyte and Environmental Samples with Silicon Nitride Nanopores: Antarctic Dirt Particulates and DNA in Artificial Seawater”, Review of Scientific Instruments, vol. 9… [cited by applicant]
Niedzwiecki, David J., et al., “Observing Changes in the Structure and Oligomerization State of a Helical Protein Dimer Using Solid-State Nanopores”, ACS Nano, vol. 9, No. 9, Aug. 11, 2015, pp. 8907-8915. [cited by applicant]
O'Hern, Sean C., et al., “Selective Ionic Transport Through Tunable Subnanometer Pores in Single-Layer Graphene Membranes”, Nano Letters, vol. 14, Issue 3, Feb. 3, 2014, pp. 1234-1241. [cited by applicant]
Rollings, Ryan C., et al., “Ion Selectivity of Graphene Nanopores”, Nature Communications, vol. 7, Apr. 22, 2016. [cited by applicant]
Rosenstein, Jacob K., et al., “Integrated Nanopore Sensing Platform with Sub-Microsecond Temporal Resolution”, Nature Methods, vol. 9, No. 5, May 2021, pp. 487-494. [cited by applicant]
Shekar, Siddharth, et al., “Measurement of DNA Translocation Dynamics in a Solid-State Nanopore at 100 ns Temporal Resolution”, Nano Letters, vol. 16, Issue 7, Jun. 22, 2016, pp. 4483-4489. [cited by applicant]
Shreiner, R.H., et al., “Primary Standards and Standard Reference Materials for Electrolytic Conductivity”, National Institute of Standards and Technology Special Publication 260-142, May 2004. [cited by applicant]
Sigel, Astrid, et al, “The Alkali Metal Ions: Their Role for Life”, Metal Ions in Life Sciences, vol. 16, 2016. [cited by applicant]
Sint, Kyaw, et al, “Selective Ion Passage Through Functionalized Graphene Nanopores”, Journal of the American Chemical Society, vol. 130, Issue 49, Nov. 14, 2008, pp. 16448-16449. [cited by applicant]
Smirnov, Ivan V., et al., “Pb EXAFS Studies on DNA Quadruplexes: Identification of Metal lon Binding Site”, Biochemistry, vol. 41, Issue 40, Sep. 7, 2002, pp. 12133-12139. [cited by applicant]
Storm, A.J., et al., “Fabrication of Solid-State Nanopores with Single-Nanometre Precision”, Nature Materials, vol. 2, Issue 8, Aug. 2003 (online: Jul. 13, 2003), pp. 537-540. [cited by applicant]