SYSTEMS AND METHODS FOR INTRAVENOUS DRUG MANAGEMENT USING IMMITTANCE SPECTROSCOPY

• US 20120065617A1
• Filed: 09/09/2011
• Published: 03/15/2012
• Est. Priority Date: 09/09/2010
• Status: Active Grant

• Current Assignee: James W. Bennett, Leonid Matsiev
• Original Assignee: S.E.A. Medical Systems Inc.
• Inventors: Matsiev, Leonid F., Weickert, Michael J., Bennett, James W., Smith, Matthew F., Litvintseva, Svetlana, Blanke, Kit
• Granted Patent: US 8,838,395 B2
• Time in Patent Office: Days
• US Class Current: 604/503
• CPC Class Codes: A61M 2205/0244 Micromachined materials, e.g. made from silicon wafers, microelectromechanical systems [MEMS] or comprising nanotechnology
• CPC Class Codes: A61M 2205/3306 Optical measuring means
• CPC Class Codes: A61M 2205/3313 used specific wavelengths
• CPC Class Codes: A61M 2205/3553 remote, e.g. between patient's home and doctor's office
• CPC Class Codes: A61M 2205/3561 local, e.g. within room or hospital
• CPC Class Codes: A61M 2205/6018 providing set-up signals for the apparatus configuration
• CPC Class Codes: A61M 5/142 Pressure infusion, e.g. using pumps
• CPC Class Codes: G01N 27/026 Dielectric impedance spectroscopy electrochemical impedance spectroscopy for measuring corrosion G01N17/02
• CPC Class Codes: G01N 27/4166 measuring a particular property of an electrolyte
• CPC Class Codes: Y02A 90/10 Information and communication technologies [ICT] supporting adaptation to climate change, e.g. for weather forecasting or climate simulation

Abstract

Described herein are devices, systems, and methods for determining the composition of liquids, including the identity of one or more drugs in the liquid, the concentration of the drug, and the type of diluent using immittance spectroscopy. These devices, systems and methods are particularly useful for describing the identity and, in some variations, concentration of one or more components of a medical liquid such as intravenous fluid. In particular, described herein are devices, systems and methods that may operate in low ionic strength diluents. Also described are methods of recognizing complex immittance spectrograph patterns to determine the composition of a liquid by pattern recognition.

Claims

1. A sensor for immittance spectroscopy configured to operate in low ionic strength liquid, the sensor comprising:

a first electrode comprising a plurality of elongate lengths of an electrically conductive material;

a second electrode comprising a plurality of elongate lengths of an electrically conductive material;

wherein the plurality of elongate lengths of electrically conductive material of the first electrode are interdigitated with the plurality of elongate lengths of electrically conducive material of the second electrode to form an electrode pair.

2. The sensor of claim 1, further comprising a second electrode pair comprising a plurality of elongate lengths of an electrically conductive material forming a third electrode and a plurality of elongate lengths of an electrically conductive material forming a fourth electrode, wherein the plurality of elongate lengths of electrically conductive material of the third electrode are interdigitated with the plurality of elongate lengths of electrically conducive material of the fourth electrode.

3. The sensor of claim 1, wherein the electrically conductive material forming the first electrode is different from the electrically conductive material forming the second electrode.

4. The sensor of claim 1, wherein the electrically conductive material forming the first electrode and the electrically conductive material forming the second electrode are selected from the group consisting of:

Au, Ti, and Pd.

5. The sensor of claim 1, wherein the elongate lengths of the first electrode are separated from the elongate lengths of the second electrode by less than 100 μ

m.

6. The sensor of claim 1, wherein the elongate lengths of the first and second electrode are curved.

7. The sensor of claim 1, further comprising a pair of electrodes configured for operation in a high ionic strength fluids.

8. The sensor of claim 1, wherein each length of the plurality of elongate lengths of the first and second electrode has a length that is greater than 10 times its width.

9. The sensor of claim 1, further comprising a printed circuit board substrate onto which the first and second electrodes are formed.

11. The sensor of claim 1 or 10, further comprising a flow sensor.

13. The sensor of claim 1, 10 or 12 further comprising a capillary port configured to wick sample liquid onto all of the electrodes of the sensor.

14. The sensor of claim 1, 10 or 12 further comprising a retractable needle configured to load sample liquid onto all of the electrodes of the sensor.

10. A sensor for immittance spectroscopy configured to operate in both high and low ionic strength liquids, the sensor comprising:

at least a first pair of electrodes configured to operate in low ionic strength liquids, the first pair comprising a first electrode having a plurality parallel elongate lengths of an electrically conductive material and a second electrode comprising a plurality of parallel elongate lengths of an electrically conductive material, wherein the elongate lengths of the first electrode are interdigitated with the elongate lengths of the second electrode; and

at least a second pair of electrodes configured to operate in high ionic strength liquids.

12. A sensor for immittance spectroscopy configured to operate in both high and low ionic strength liquids, the sensor comprising:

three pairs of electrodes configured to operate in low ionic strength liquids, wherein each first pair comprises a first electrode having a plurality parallel elongate lengths of an electrically conductive material and a second electrode comprising a plurality of parallel elongate lengths of an electrically conductive material, wherein the elongate lengths of the first electrode for a pair are interdigitated with the elongate lengths of the second electrode for that pair; and

three electrodes configured to operate in high ionic strength liquids.

15. An immittance spectroscopy system configured to operate in low ionic strength liquids, the system comprising:

a sensor having at least one pair of electrodes configured to operate in a low ionic strength liquid;

a signal generator configured to provide electrical excitation at a plurality of frequencies including a low frequency range from less than about 100 milliHertz to greater than about 1 KHz;

a processor configured to receive complex admittance data from the sensor at the plurality of frequencies and to determine the identity, concentration or the identity and the concentration of one or more compounds in the liquids.

16. The system of claim 15, wherein the sensor comprises at least a first pair of electrodes configured to operate in low ionic strength liquids, the first pair comprising a first electrode having a plurality parallel elongate lengths of an electrically conductive material and a second electrode comprising a plurality of parallel elongate lengths of an electrically conductive material, wherein the elongate lengths of the first electrode are interdigitated with the elongate lengths of the second electrode.

17. The system of claim 15, wherein the signal generator is configured to provide electrical excitation at a plurality of frequencies including a low frequency range from less than about 100 milliHertz to greater than about 100 KHz.

18. An immittance spectroscopy system configured to operate in both low and high ionic strength liquids, the system comprising:

a sensor having at least one pair of electrodes configured to operate with a low ionic strength liquid and at least one pair of electrodes configured to operate with a high ionic strength liquid;

a signal generator configured to provide electrical excitation at a plurality of frequencies including a low frequency range from less than about 100 milliHertz to greater than about 10 KHz;

a processor configured to receive complex admittance data from either or both pairs of electrodes of the sensor at the plurality of frequencies and to determine the identity, concentration or the identity and the concentration of one or more compounds in the liquids.

19. The system of claim 18, wherein the pair of electrodes configured to operate in low ionic strength liquids comprises a first electrode having a plurality parallel elongate lengths of an electrically conductive material and a second electrode comprising a plurality of parallel elongate lengths of an electrically conductive material, wherein the elongate lengths of the first electrode are interdigitated with the elongate lengths of the second electrode.

20. A method of determining the identify and/or concentration of a drug in a low ionic strength liquid, the method comprising:

contacting a low ionic strength liquid and an electrode pair comprising a first electrode having a plurality parallel elongate lengths of an electrically conductive material and a second electrode comprising a plurality of parallel elongate lengths of an electrically conductive material, wherein the elongate lengths of the first electrode are interdigitated with the elongate lengths of the second electrode;

applying electrical excitation to the liquid at a plurality of frequencies including a low frequency range from less than about 100 milliHertz to greater than about 1 Hz; and

determining the identity, concentration or identity and concentration of one or more compounds in the liquid based on a complex immittance measured between the electrode pair.

21. The method of claim 20, wherein contacting the low ionic strength liquid comprises contacting the low ionic strength liquid and a plurality of electrode pairs each having a first electrode with a plurality of parallel elongate lengths and a second electrode with a plurality of parallel elongate lengths, wherein the elongate lengths of the first electrode are interdigitated with the elongate lengths of the second electrode.

22. The method of claim 20, further comprising contacting the low ionic strength liquid and at least one pair of electrodes configured to measure complex immittance in high ionic strength liquids.

23. The method of claim 20, wherein applying electrical excitation comprises applying electrical excitation at a plurality of frequencies including a low frequency range from less than about 100 milliHertz to greater than about 1 KHz.

24. The method of claim 20, wherein applying electrical excitation comprises applying electrical excitation to the electrode pair.

25. The method of claim 20, wherein applying electrical excitation results in a voltage that is below a threshold level for electrochemical reaction at the surfaces of the first and second electrodes.

26. The method of claim 20, wherein applying electrical excitation results in a voltage that is below 500 mV.

27. The method of claim 20, further comprising recording the complex immittance at a plurality of the applied frequencies.

28. The method of claim 20, wherein determining comprises comparing the complex immittance with a library of complex immittances.

29. A method of determining the identify and/or concentration of a drug in a low or high ionic strength liquid, the method comprising:

contacting a liquid and both a low ionic strength electrode pair and a high ionic strength electrode pair;

applying electrical excitation to the electrodes at a plurality of frequencies from less than about 100 milliHertz to greater than about 1 KHz;

detecting the complex immittance at both the low ionic strength electrode pair and the high ionic strength electrode pair; and

determining the identity, concentration or identity and concentration of one or more compounds in the liquid based on either or both the complex immittances measured between the low ionic strength electrode pair and the high ionic strength electrode pair.

30. The method of claim 29, wherein contacting the liquid and the low ionic strength electrode pair comprises comprising a first electrode having a plurality parallel elongate lengths of an electrically conductive material and a second electrode comprising a plurality of parallel elongate lengths of an electrically conductive material, wherein the elongate lengths of the first electrode are interdigitated with the elongate lengths of the second electrode.

31. The method of claim 29, further comprising determining if the liquid is high ionic strength or low ionic strength.

32. The method of claim 29, wherein contacting comprises contacting the liquid with a plurality of both low ionic strength electrode pairs and a high ionic strength electrode pairs.

33. The method of claim 29, wherein applying electrical excitation comprises applying electrical excitation to the electrodes at a plurality of frequencies from less than about 100 milliHertz to greater than about 10 KHz.

34. The method of claim 29, further comprising recording the complex immittance at both the low ionic strength electrode pair and the high ionic strength electrode pair.

35. The method of claim 29, wherein applying electrical excitation comprises applying electrical excitation to the electrode pair.

36. The method of claim 29, wherein applying electrical excitation results in a voltage that is below a threshold level for electrochemical reaction at the surfaces of the electrodes.

37. The method of claim 29, wherein applying electrical excitation results in a voltage that is below 500 mV.

38. The method of claim 29, wherein determining comprises comparing the complex immittance against a library of complex immittances.

39. The method of claim 29, wherein determining comprises comparing the complex immittances at a plurality of frequencies against a library of complex immittances.

40. A system for collecting and identifying drug waste in a liquid, the system comprising:

a waste input port to receive liquid drug waste;

a sample chamber coupled to the waste input port, wherein the sample chamber comprises a plurality of electrode pairs configured to contact received liquid drug waste;

a signal generator configured to provide electrical energy to liquid drug waste within the sample chamber at a plurality of frequencies;

a processor configured to receive complex immittance information at a plurality of frequencies from the plurality of electrode pairs, and to determine the identity and amount of drug in the liquid drug waste; and

a collection chamber to collect liquid drug waste.

41. The system of claim 40, further comprising a plurality of collection chambers.

42. The system of claim 40, further comprising a replaceable cartridge holding the plurality of electrode pairs.

43. The system of claim 40, wherein the sample chamber is a flow-through chamber configured to pass liquid drug waste therethrough, and further wherein the sample chamber and plurality of electrode pairs are part of a replaceable cartridge.

44. The system of claim 40, further comprising a flow sensor to determine the flow rate of liquid drug waste entering the input port.

45. The system of claim 40, wherein the signal generator is configured to provide electrical energy at a plurality of frequencies from less than about 100 milliHertz to greater than about 10 Hz.

46. The system of claim 40, wherein the processor is configured to log and/or report the identity and amount of drug in a received liquid drug waste.

47. The system of claim 40, further comprising an output to report the identity and amount of drug received.

48. The system of claim 40, wherein the processor is configured to direct the collection of liquid drug waste to one of a plurality of collection chambers based on the identity of the drug in a received liquid drug waste.

49. The system of claim 40, further comprising rinse module connected to a source of rinsate to rinse the sample chamber after delivery of a liquid drug waste.

50. The system of claim 40, wherein the processor is configured to compare determine the identity and amount of drug in the liquid drug waste received by comparing the complex immittance to a library of complex immittances of known drugs.

51. A system for collecting and identifying drug waste in a liquid, the system comprising:

a waste input port to receive liquid drug waste;

a sample chamber coupled to the waste input port, wherein the sample chamber comprises a plurality of electrode pairs configured to contact received liquid drug waste;

a flow sensor configured to determine the flow of liquid into the system;

a signal generator configured to provide electrical energy to liquid drug waste within the sample chamber at a plurality of frequencies;

a processor configured to receive complex immittance information at a plurality of frequencies from the plurality of electrode pairs, and to determine the identity and amount of drug in the liquid drug waste from the immittance information and the flow sensor; and

a collection chamber to collect liquid drug waste.

52. A system for collecting and identifying drug waste in a liquid, the system comprising:

a waste input port to receive liquid drug waste;

a sample chamber coupled to the waste input port, wherein the sample chamber comprises a plurality of electrode pairs configured to contact received liquid drug waste;

a signal generator configured to provide electrical energy to liquid drug waste within the sample chamber at a plurality of frequencies;

a processor configured to receive complex immittance information for a plurality of frequencies from the plurality of electrode pairs, and to determine the identity and amount of drug in a received liquid drug waste from the complex immittance information; and

a plurality of collection chambers to collect liquid drug waste, wherein the processor directs the collection of liquid drug waste to one of the plurality of collection chambers based on the identity of the drug in a received liquid drug waste.

53. A method of collecting and identifying drug waste in a liquid, the method comprising:

receiving a liquid drug waste;

determining complex immittance information from the liquid drug waste using each of a plurality of electrode pairs for a plurality of frequencies;

determining the identity and amount of drug in the liquid drug waste; and

collecting the liquid drug waste in a collection chamber.

54. The method of claim 53, further comprising recording the amount of drug in the liquid waste received.

55. The method of claim 53, wherein receiving the liquid drug waste comprises pumping the liquid drug waste into a waste input port of a system for collecting and identifying drug waste in a liquid.

56. The method of claim 53, wherein determining complex immittance information comprises applying electrical energy at a plurality of frequencies across the plurality of electrode pairs when they are in contact with the liquid drug waste.

57. The method of claim 53, wherein determining the identity and amount of drug comprises using the complex immittance information to determine the identity and amount of drug in the liquid drug waste.

58. The method of claim 53, wherein determining the identity and amount of drug comprises comparing the complex immittance information with a library of complex immittance information of known drugs to determine the identity and amount of drug in the liquid drug waste.

59. The method of claim 53, wherein collecting the liquid drug waste comprises collecting liquid drug waste containing different drugs into different collection chambers.

60. A method of determining the identity of a drug or drug formulation by recognizing a pattern of complex immittance from a library of known complex immittances, the method comprising:

receiving an initial dataset comprising complex immittance spectrographic information for an unknown liquid sample, the complex immittance spectrographic information taken from a plurality of different electrode pairs at a plurality of different frequencies;

using a processor to apply one or more pattern recognition techniques to compare the initial dataset to an identification space database comprising a plurality of identification datasets wherein the identification datasets comprise complex immittance data corresponding to known drug compositions to determine if the initial dataset matches an identification dataset from the identification space database within a threshold range; and

reporting that the initial dataset does or does not match an identification dataset, and if the initial dataset does match an identification dataset within the threshold range, reporting which drug or drugs correspond to the identification dataset matched.

61. The method of claim 60, wherein using the processor to apply one or more pattern recognition techniques comprises using a Neural Network.

62. The method of claim 60, wherein using the processor to apply one or more pattern recognition techniques comprises using a Probabilistic Neural Network.

63. The method of claim 60, wherein using the processor to apply one or more pattern recognition techniques comprises reducing the dimension of the initial dataset and performing a regression analysis.

64. The method of claim 60, wherein receiving the initial dataset comprises receiving an initial dataset having greater than 30 dimensions.

65. The method of claim 60, further comprising setting the threshold range.

66. The method of claim 60, wherein using a processor to apply one or more pattern recognition techniques comprises applying two pattern recognition techniques.

67. The method of claim 60, wherein using the processor to apply one or more pattern recognition techniques comprises initially applying a PCA method to reduce the dimension of the data and then applying another pattern recognition technique to determine if the initial dataset matches an identification dataset.

68. The method of claim 60, wherein using the processor to apply one or more pattern recognition techniques comprises initially applying a PCA method to reduce the dimension of the dataset and then using a neural network to determine if the initial dataset matches an identification dataset.

69. The method of claim 60, wherein using the processor to apply one or more pattern recognition techniques comprises applying a linear technique selected from the group consisting of principal component analysis, factor analysis, projection pursuit, independent component analysis, multi-objective functions, one-unit objective functions, adaptive methods, batch-mode algorithms, and random projections methods.

70. The method of claim 60, wherein using the processor to apply one or more pattern recognition techniques comprises applying a non-linear technique selected from the group consisting of:

non-linear principle component analysis, non-linear independent component analysis, principle curves, multidimensional scaling, and topologically continuous maps.

71. The method of claim 60, further comprising interpolating to get an estimate of the concentration of the drug or drug corresponding to the matching identification dataset when the initial dataset matches the identification dataset within the threshold range.

72. The method of claim 60, wherein reporting that the initial dataset does or does not match an identification dataset comprises reporting the concentration of the drug or drugs correspond to the identification dataset when the initial dataset does match the identification dataset within the threshold range.

73. The method of claim 60, wherein using the processor to apply one or more pattern recognition techniques comprises reducing the initial dataset down to four dimensions.

74. A method of determining the identity of a drug or drug formulation by recognizing a pattern of complex immittance from a library of known complex immittances, the method comprising:

receiving an initial dataset comprising multi-dimensional, complex immittance spectrographic information for an unknown liquid sample, the complex immittance spectrographic information taken from a plurality of different electrode pairs at a plurality of different frequencies;

reducing the dimensions of the initial dataset using a linear or non-linear technique to form a reduced dataset;

determining how closely the reduced dataset matches an identification dataset of an identification space database, wherein the identification space database comprises a plurality of identification datasets corresponding to known drug compositions; and

reporting that the known drug composition corresponding to the identification space database having the closest match to the reduced dataset if the closeness of the match is within a threshold range, or report that the unknown liquid sample does not match a known drug composition of those drugs included in the identification space database if the closeness of match is outside of the threshold range.

75. The method of claim 74, wherein reducing the dimensions of the initial dataset comprises applying a linear technique selected from the group consisting of:

principal component analysis, factor analysis, projection pursuit, independent component analysis, multi-objective functions, one-unit objective functions, adaptive methods, batch-mode algorithms, and random projections methods.

76. The method of claim 74, wherein reducing the dimensions of the initial dataset comprises applying a non-linear technique selected from the group consisting of:

non-linear principle component analysis, non-linear independent component analysis, principle curves, multidimensional scaling, and topologically continuous maps.

77. The method of claim 74, wherein reducing the dimensions of the initial dataset comprises reducing the initial dataset down to four dimensions.

78. A method of determining the identity and concentration of a drug by recognizing a pattern of complex immittance from a library of known complex immittance s, the method comprising:

receiving an initial dataset comprising multi-dimensional, complex immittance spectrographic information for an unknown liquid sample, the complex immittance spectrographic information taken from a plurality of different electrode pairs at a plurality of different frequencies;

reducing the dimensions of the initial dataset using a linear or non-linear technique to form a reduced dataset;

matching the reduced dataset to an identification space database, the identification space database comprising a plurality of identification datasets corresponding to known drug compositions;

determining the closeness of the match for the reduced dataset relative to each of the identification datasets;

determining a proposed drug composition by applying a threshold to the closeness of the match for each of the identification datasets, wherein the proposed drug composition is unknown if the closeness of match is outside of the threshold range; and

determining a concentration of drug in the unknown liquid sample by applying a regression of the proposed drug composition for the known drug composition.

79. A fully automated medical system configured to monitor a patient and deliver necessary medication, the system comprising:

a patient monitor configured to receive information on a patient'"'"'s health;

a processor configured to receive information on the patient'"'"'s health from the patient monitor and to prepare and administer an intravenous drug based on the patient'"'"'s health;

an IV drug compounding system in communication with the processor and configured to compound a drug requested by the processor, wherein the IV drug compounding system confirms the drug identity and concentration after compounding; and

an IV drug delivery system comprising a drug pump, the IV drug delivery system in communication with the IV drug compounding system and the processor, wherein IV drug delivery system confirms the identity and concentration of the IV drug as it is being delivered to the patient.

80. A method for accurately and automatically delivering a drug to a patient, the method comprising:

electronically communicating medical information about a patient to an automatic IV delivery system, wherein the automatic IV delivery system determines a drug and drug dosage from the patient'"'"'s medical information; and

administering a drug solution comprising the determined drug and drug dosage to the patient using the automatic IV delivery system, wherein the automatic IV delivery system monitors and confirms the composition of the drug solution as it is being administered.

81. The method of claim 80, further comprising connecting the patient to the automatic IV delivery system.

82. The method of claim 80, further comprising automatically compounding the drug solution with the automatic IV delivery system.

83. The method of claim 82, wherein the automatic IV delivery system confirms that the composition of the drug solution is correct prior to administering the drug solution.

84. The method of claim 80, further comprising confirming the identity of the patient.

85. The method of claim 80, wherein the automatic IV delivery system comprises an immittance spectrographic system that confirms the composition of the drug solution by determining a complex immittance fingerprint from the drug solution.

86. A method for accurately and automatically delivering a drug to a patient, the method comprising:

electronically communicating medical information about a patient to an automatic IV delivery system, wherein the automatic IV delivery system determines a drug and drug dosage from the patient'"'"'s medical information;

compounding a drug solution of the determined drug, wherein the automatic IV delivery system confirms that the composition of the drug solution corresponds to the drug and dose from the patient'"'"'s medical information;

administering a drug solution comprising the determined drug and drug dosage to the patient using the automatic IV delivery system, wherein the automatic IV delivery system includes a pump and monitors and confirms the composition of the drug solution as it is being administered.