Glucose sensor apparatus addressing interference of ascorbic acid and acetaminophen

• US 10,327,684 B2
• Filed: 12/18/2017
• Issued: 06/25/2019
• Est. Priority Date: 11/21/2017
• Status: Active Grant

• Current Assignee: UXN Co., Ltd.
• Original Assignee: UXN Co., Ltd.
• Inventors: Park, Sejin, Chang, Rae Kyu, Boo, Hankil
• Primary Examiner(s): Natnithithadha, Navin
• Assistant Examiner(s): Tran, Tho Q
• Application Number:
  US15/845,668
• Publication Number:
  US 20190150812A1
• Time in Patent Office: 554 Days
• Field of Search: 600365
• CPC Class Codes: A61B 2560/0475 Special features of memory means, e.g. removable memory cards
• CPC Class Codes: A61B 2562/0285 Nanoscale sensors
• CPC Class Codes: A61B 2562/125 characterised by the manufacture of electrodes
• CPC Class Codes: A61B 5/0031 Implanted circuitry
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/1473 invasive, e.g. introduced into the body by a catheter A61B5/1482 takes precedence
• CPC Class Codes: A61B 5/1486 using enzyme electrodes, e.g. with immobilised oxidase
• CPC Class Codes: A61B 5/14865 invasive, e.g. introduced into the body by a catheter or needle or using implanted sensors
• CPC Class Codes: A61B 5/72 Signal processing specially adapted for physiological signals or for diagnostic purposes character recognition, recognising digital ink, document-oriented image-based pattern recognition G06V30/00; recognition or understanding of postal images G06V30/424
• CPC Class Codes: A61B 5/742 using visual displays A61B5/339 takes precedence
• CPC Class Codes: B01J 13/0013 from a precipitate
• CPC Class Codes: B05D 5/00 Processes for applying liquids or other fluent materials to surfaces to obtain special surface effects, finishes or structures
• CPC Class Codes: B05D 5/02 to obtain a matt or rough surface
• CPC Class Codes: B82Y 15/00 Nanotechnology for interacting, sensing or actuating, e.g. quantum dots as markers in protein assays or molecular motors
• CPC Class Codes: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: B82Y 40/00 Manufacture or treatment of nanostructures
• CPC Class Codes: C09D 5/028 Pigments; Filters
• CPC Class Codes: C09D 5/24 Electrically-conducting paints conductive materials H01B1/00
• CPC Class Codes: C09D 7/67 Particle size smaller than 100 nm
• CPC Class Codes: C12Q 1/006 for glucose
• CPC Class Codes: G01N 2400/00 : Assays, e.g. immunoassays or enzyme assays, involving carbohydrates
• CPC Class Codes: G01N 27/327 : Biochemical electrodes , e.g. electrical or mechanical details for in vitro measurements
• CPC Class Codes: G01N 27/3271 : Amperometric enzyme electrodes for analytes in body fluids, e.g. glucose in blood amperometry per se G01N27/49; aspects concerning the enzyme reagent C12Q1/001
• CPC Class Codes: G01N 27/3335 : the membrane containing at least one organic component G01N27/3271 takes precedence; aspects concerning the enzyme reagent in enzyme electrodes C12Q1/001
• CPC Class Codes: G01N 27/4168 : Oxidation-reduction potential, e.g. for chlorination of water water analysis G01N33/18
• CPC Class Codes: G01N 33/49 : Blood chemical methods for determining blood cell populations G01N33/5094; chemical analysis of blood groups or blood types G01N33/80
• CPC Class Codes: G01N 33/66 : involving blood sugars, e.g. galactose
• CPC Class Codes: Y10S 977/773 : Nanoparticle, i.e. structure having three dimensions of 100 nm or less
• CPC Class Codes: Y10S 977/81 : Of specified metal or metal alloy composition
• CPC Class Codes: Y10S 977/896 : Chemical synthesis, e.g. chemical bonding or breaking
• CPC Class Codes: Y10S 977/92 : Detection of biochemical

Abstract

This disclosure relates to a nanoporous composition including a number of clusters of nanoparticles dispersed in a liquid, a nanoporous layer formed of the nanoporous composition, a glucose-oxidation electrode including the nanoporous layer, and a glucose-sensing device and system including the glucose-oxidation electrode. This disclosure also relates to a method of making the nanoporous composition, the nanoporous layer, the glucose-oxidation electrode and the glucose-sensing device and system. Further, this disclosure also relates to devices, systems and methods for continuous glucose monitoring (CGM) and blood glucose monitoring (BGM).

Claims

1. An apparatus, comprising:

a substrate;

a first electrode comprising a first electrically conductive layer formed over a first electrode location of the substrate and a glucose-oxidation layer formed over the first electrically conductive layer;

a first terminal formed over a first terminal location of the substrate and electrically connected to the first electrode;

a second electrode comprising a second electrically conductive layer formed over a second electrode location of the substrate;

a second terminal formed over a second terminal location of the substrate and electrically connected to the second electrode;

a reference electrode comprising a third electrically conductive layer formed over a reference electrode location of the substrate; and

a third terminal formed over a third terminal location of the substrate and electrically connected to the reference electrode,

wherein, when the first electrode contacts liquid containing glucose and ascorbic acid and acetaminophen and when applying a first bias voltage between the first and reference electrodes that is sufficient to oxidize glucose in the glucose-oxidation layer, the glucose-oxidation layer of the first electrode is configured to cause oxidation of glucose and at least one of ascorbic acid and acetaminophen therein and further configured to generate a first electric current comprising a glucose component caused by the glucose oxidation and a first interference component caused by oxidation of at least one of ascorbic acid and acetaminophen in the glucose-oxidation layer,

wherein the second electrode is arranged in the apparatus such that, when the first electrode contacts the liquid, the second electrode also contacts the same liquid,

wherein the second electrode does not comprise a layer configured to cause oxidation of glucose therein such that, when applying a second bias voltage between the second and reference electrodes, the second electrode is configured to cause oxidation of at least one of ascorbic acid and acetaminophen therein but not to cause oxidation of glucose therein and further configured to generate a second electric current comprising a second interference component caused by oxidation of at least one of ascorbic acid and acetaminophen in the second electrode and not caused by oxidation of glucose,

wherein the apparatus is configured to provide the first electric current at the first terminal and the second electric current at the second terminal,

wherein the glucose-oxidation layer comprises a deposit of irregularly shaped bodies that are formed of numerous nanoparticles having a generally oval or spherical shape with a length ranging between about 2 nm and about 5 nm,

wherein adjacent ones of the irregularly shaped bodies abut one another while forming unoccupied spaces between non-abutting surfaces or portions of the adjacent ones of the irregularly shaped bodies,

wherein abutments between adjacent ones of the irregularly shaped bodies connect the adjacent ones with one another, which continues to other ones of the irregularly shaped bodies to form a three-dimensional interconnected network of irregularly shaped bodies,

wherein the unoccupied spaces between non-abutting surfaces or portions of the adjacent ones of the irregularly shaped bodies are irregularly shaped and connect with other unoccupied spaces formed by other ones of the irregularly shaped bodies,

wherein connections between the unoccupied spaces form a three-dimensional interconnected network of irregularly shaped spaces that is geometrically complementary to and outside the three-dimensional interconnected network of irregularly shaped bodies inside the glucose-oxidation layer,

wherein, inside the three-dimensional interconnected network of irregularly shaped bodies, at least part of the nanoparticles are adjacent to each other without an intervening nanoparticle therebetween and apart from each other to define interparticular nanopores therebetween,

whereby the glucose-oxidation layer comprises the interparticular nanopores inside the three-dimensional interconnected network of irregularly shaped bodies and further comprises the three-dimensional interconnected network of irregularly shaped spaces outside the three-dimensional interconnected network of irregularly shaped bodies,

wherein at least part of the interparticular nanopores inside the three-dimensional interconnected network of irregularly shaped bodies are in a size ranging between about 0.5 nm and about 3 nm,

wherein at least part of the irregularly shaped spaces of the three-dimensional interconnected network of irregularly shaped spaces are in a size ranging between about 100 nm and about 500 nm,

wherein the glucose-sensing electrode does not comprise a glucose-specific enzyme,

wherein the glucose-oxidation layer is substantially free of a surfactant, wherein if any surfactant is contained in the glucose-oxidation layer, the surfactant is in an amount smaller than 0.5 parts by weight with reference to 100 parts by weight of the deposit.

2. The apparatus of claim 1, wherein the apparatus is configured to provide the second electric current in connection with the first electric current when providing the first electric current.

3. The apparatus of claim 1, wherein the apparatus is configured to generate the first electric current and the second electric current at the same time.

4. The apparatus of claim 1, wherein the apparatus is configured to provide the first electric current and the second electric current along with information indicative of time of generating the first electric current and the second electric current.

5. The apparatus of claim 1, wherein the apparatus is configured to provide the second electric current together with the first electric current whenever providing the first electric current.

6. The apparatus of claim 1, wherein the first electric current further comprises a first background current caused by other electrochemical interactions of the liquid and the glucose-oxidation layer, wherein the second electric current further comprises a second background current caused by other electrochemical interactions of the liquid and the second electrode.

7. The apparatus of claim 1, wherein, when applying a voltage between 0.2 V and 0.32 V as the first bias voltage, the glucose-oxidation layer is configured to oxidize glucose and ascorbic acid but not acetaminophen, and the first interference component is caused by oxidation of ascorbic acid and not by oxidation of acetaminophen,

wherein, when applying a voltage between 0.2 V and 0.32 V as the second bias voltage, the second electrode is configured to oxidize ascorbic acid but not acetaminophen and the second interference component is caused by oxidation of ascorbic acid and not by oxidation of acetaminophen.

8. The apparatus of claim 1, wherein, when applying a voltage between 0.34 V and 0.45 V as the first bias voltage, the glucose-oxidation layer is configured to oxidize glucose, ascorbic acid and acetaminophen, and the first interference component is caused by oxidation of ascorbic acid and acetaminophen,

wherein, when applying a voltage between 0.34 V and 0.45 V as the second bias voltage, the second electrode is configured to oxidize ascorbic acid and acetaminophen and the second interference component is caused by oxidation of both ascorbic acid and acetaminophen.

9. The apparatus of claim 1, wherein the first electrode further comprises a maltose-blocking layer comprising poly-phenylenediamine (poly-PD) formed over the glucose-oxidation layer,

wherein, when contacting liquid containing glucose with a concentration of 4-20 mM (72-360 mg/dL) and when applying the bias voltage, the maltose-blocking layer is configured to let glucose pass therethrough and substantially block maltose from passing therethrough such that at steady state the glucose-oxidation current is at a level higher than 0.1 μ

A/mMcm² (10 nA/mMcm²) while a maltose oxidation current caused by oxidation of maltose alone is lower than 0.05 μ

A/mMcm² (5 nA/mMcm²).

10. The apparatus of claim 1, wherein the apparatus is a continuous glucose monitoring (CGM) electrode module comprising a subcutaneous portion configured to subcutaneously contact bodily fluid of a subject, wherein the first, second and reference electrodes are formed in the subcutaneous portion.

11. The apparatus of claim 1, wherein the first bias voltage is between 0.2 V and 0.45 V, wherein the second bias voltage is the same as or different from the first bias voltage, wherein the glucose-oxidation layer comprises a nanoporous metal material or a glucose-specific enzyme configured to oxidize glucose.

12. The apparatus of claim 1, wherein the three-dimensional interconnected network of irregularly shaped bodies further comprises interparticular nanopores between adjacent nanoparticles in a size ranging between about 0.25 nm and about 4.5 nm.

13. A system comprising:

the sensor apparatus of claim 1 further comprising a terminal portion in which the first, second and third terminals are arranged;

a counterpart apparatus comprising a first counterpart terminal, a second counterpart terminal, a third counterpart terminal, circuitry, and an electric power connected to the circuitry; and

the counterpart apparatus further comprising a counterpart terminal portion configured to connect or engage with the terminal portion,

wherein the first, second and third counterpart terminals are arranged in the counterpart terminal portion such that, when the terminal portion of the sensor apparatus and the counterpart terminal portion of the counterpart apparatus are connected or engaged, the first terminal electrically connects to the first counterpart terminal, the second terminal electrically connects to the second counterpart terminal, and the third terminal electrically connects to the third counterpart terminal,

wherein the circuitry of the counterpart apparatus is configured to provide the first bias voltage between the first counterpart terminal and the third counterpart terminal,

wherein the circuitry of the counterpart apparatus is further configured to provide the second bias voltage between the second counterpart terminal and the third counterpart terminal.

14. The system of claim 13, wherein the counterpart apparatus comprises a wireless communication module configured to wirelessly communicate with a wirelessly paired computing device that comprises at least one processor and at least one memory, wherein the counterpart apparatus is configured to receive the first electric current at the first counterpart terminal and the second electric current at the second counterpart terminal, wherein the counterpart apparatus is further configured to transmit the second electric current together or in connection with the first electric current when transmitting the first electric current.

15. The system of claim 14, wherein the first electric current is transmitted with a first time stamp, and the second electric current is transmitted with a second time stamp, wherein the first and second time stamps indicate an identical time.

16. The system of claim 14, further comprising:

software installed and executable by the at least one processor of the wirelessly paired computing device,

wherein upon execution the software is configured to perform a method comprising;

causing to store, in the at least one memory of the computing device, the first electric current and the second electric current received together or in connection with each other from the counterpart apparatus;

processing the first electric current and the second electric current to provide a value indicative of the oxidation of glucose in the glucose-oxidation layer of the first electrode of the sensor apparatus; and

causing to present the value or its corresponding information on a display of the computing device.

17. The system of claim 14, wherein either or both of the first electric current and the second electric current are in the form of continuous signals, wherein processing the first electric current and the second electric current comprises processing values of the first electric current and the second electric current obtained at the same time.

18. The system of claim 17, wherein processing comprises subtracting the second electric current from the first electric current.

19. The system of claim 17, wherein the first electric current and the second electric current are stored in connection with each other in the at least one memory.

20. The system of claim 14, further comprising:

software installed and executable by the at least one processor of the wirelessly paired computing device,

wherein upon execution the software is configured to perform data processing to obtain a level of glucose contained in the liquid that the first electrode of the sensor apparatus contacts using the first electric current and the second electric current received from the counterpart apparatus, wherein the software requires the second electric current when processing to obtain the level of glucose.

21. The system of claim 13, wherein the counterpart apparatus further comprises at least one processor, at least one memory, and software stored in the at least one memory and executable by the at least one processor, wherein upon execution the software is configured to perform a method comprising:

causing to store, in the at least one memory, the first electric current and the second electric current received together or in connection with each other from the sensor apparatus; and

processing the first electric current and the second electric current to provide a value indicative of the oxidation of glucose in the glucose-oxidation layer of the first electrode of the sensor apparatus.

22. The system of claim 21, wherein processing comprises subtracting the second electric current from the first electric current.

23. The system of claim 21, wherein either or both of the first electric current and the second electric current are in the form of continuous signals, wherein processing the first electric current and the second electric current comprises processing values of the first electric current and the second electric current obtained at the same time.

24. The system of claim 21, wherein the counterpart device further comprises a display, wherein the method further comprises causing to present the value or its corresponding information on the display.

25. The system of claim 21, wherein the counterpart device further comprises a wireless communication module configured to wirelessly pair with a device that comprises a display, wherein the method further comprises causing to transmit data to the wirelessly paired device for presenting the value or its corresponding information on the display of the wirelessly paired device.