Infection-sensing medical systems and methods

Abstract

An infection-sensing medical system can include an indwelling medical device and a dedicated computing device. The indwelling medical device can include an intracorporeal conduit configured to be percutaneously inserted into a blood vessel of a patient and a microcontroller integrated into a portion of the indwelling medical device. The microcontroller can include a chemical-sensor module and one or more chemical sensors configured to generate electrical signals in response to interactions with one or more volatile organic chemicals ("VOCs") associated with the patient. The microcontroller can also include a microcontroller processor configured to generate chemical-sensor data from the electrical signals. The dedicated computing device can include a computing-device processor configured to generate one or more observed chemical signatures from the chemical-sensor data as well as determine whether the patient has a microbial infection by comparison of the one-or-more observed chemical signatures to known chemical signatures for microbial infections.

Description

INFECTION-SENSING MEDICAL SYSTEMS AND METHODSPRIORITY

[0001] This application claims the benefit of priority to U.S. Provisional Patent Application No. 63 / 527,293, filed luly 17, 2023, which is incorporated by reference in its entirety into this application.BACKGROUND

[0002] Catheter-related bloodstream infections (“CRB Sis”) are among the most frequent infections acquired in hospitals. Current estimates are that between 15% and 30% of all nosocomial bacteremias are catheter-related. The incidence of catheter-related infections varies considerably depending on the type of catheter and intended use, the insertion site, the experience and training of the clinician who places the catheter, the frequency with which the catheter is accessed, duration of catheter placement, the characteristics of the patient, and the use of proven prevention strategies. Notably, patients needing medical interventions are typically also at higher risk for serious infections involving the blood and the whole body (sepsis). In recent years, there has been a remarkable increase in our knowledge of the epidemiology of CRB Sis and of the most appropriate methodologies for diagnosis, management, and prevention. However, CRB Sis still have significant associated morbidity, incur increased hospital costs, estimated at almost USS 20K per episode, and length of stay. Attributable mortality ranges between 12% and 25%.

[0003] Disclosed herein are infection-sensing medical systems and methods that address the foregoing.SUMMARY

[0004] Disclosed herein is an infection-sensing medical system including, in some embodiments, an indwelling medical device and a dedicated computing device. The indwelling medical device includes an intracorporeal conduit, one or more extracorporeal conduits fluidly connected to the intracorporeal conduit, a hub between a proximal portion of the intracorporeal conduit and one or more respective distal portions of the one-or-more extracorporeal conduits, and a microcontroller integrated into a portion of the indwelling medical device. The intracorporeal conduit is configured to be percutaneously inserted into a blood vessel of a patient. The one-or-more extracorporeal conduits are configured to remain outside a body ofthe patient. The microcontroller includes a chemical-sensor module and a microcontroller processor. The chemical-sensor module includes one or more chemical sensors configured to generate electrical signals in response to interactions with one or more volatile organic chemicals (“VOCs”) associated with the patient. The microcontroller processor is configured to generate chemical-sensor data from the electrical signals. The dedicated computing device includes a computing-device processor configured to generate one or more observed chemical signatures from the chemical-sensor data. In addition, the computing-device processor is configured to determine whether the patient has a microbial infection by comparison of the one-or-more observed chemical signatures to known chemical signatures for microbial infections.

[0005] In some embodiments, the indwelling medical device further includes one or more respective connectors of the one-or-more extracorporeal conduits. The portion of the indwelling medical device in which the microcontroller is integrated is a connector of the one- or-more connectors.

[0006] In some embodiments, the portion of the indwelling medical device in which the microcontroller is integrated is the hub.

[0007] In some embodiments, the microcontroller further includes a microcontroller communications module configured for wireless communications with a computing-device communications module of the dedicated computing device. The wireless communications include at least the chemical-sensor data.

[0008] In some embodiments, the microcontroller further includes memory configured to store the chemical-sensor data over time. The one-or-more observed chemical signatures generated by the computing-device processor include a plurality of time-dependent observed chemical signatures in accordance with the chemical-sensor data stored in the memory over time.

[0009] In some embodiments, the one-or-more observed chemical signatures are at least semi-quantitative with respect to one or more constituent VOCs thereof. The plurality of time-dependent observed chemical signatures thereby indicate semi-quantitative changes in the one-or-more constituent VOCs over time and, thus, any changes with respect to patient condition over time.

[0010] In some embodiments, the indwelling medical device further includes a VOC- permeable membrane over the chemical-sensor module. The VOC-permeable membrane is configured to selectively allow the one-or-more VOCs therethrough over water vapor.

[0011] In some embodiments, the one-or-more VOCs are selected from indole, methanol, 1 -undecene, ethyl acetate, 2,4-dimethyl-l -heptane, 2-butanone, benzaldehyde, dimethylcyclohexanol, isovaleric acid, 2-pentanol, 4-methyl-quinazoline, and 2-methyl- butanal.

[0012] In some embodiments, the known chemical signatures for microbial infections are selected from a Staphylococcus aureus chemical signature including some combination of benzaldehyde, isovaleric acid, and 2-methyl-butanal; a Pseudomonas aeruginosa chemical signature including some combination of 1 -undecene, 2,4-dimethyl-l -heptane, 2-butanone, 2- pentanol, and 4-methyl-quinazoline; an Escherichia coli chemical signature including some combination of indole, methanol, ethyl acetate, and 2-pentanol; a Clostridium sporogenes chemical signature including some combination of indole, methanol, ethyl acetate, and 2- pentanol; and a Candida albicans chemical signature including some combination of methanol and dimethyl cyclohexanol.

[0013] In some embodiments, the medical system further includes a wound dressing sized to cover an insertion site, any portion of the intracorporeal conduit of the indwelling medical device extending from the insertion site, and the hub of the indwelling medical device. The wound dressing includes a water vapor-permeable membrane configured to selectively allow water vapor therethrough over the one-or-more VOCs.

[0014] In some embodiments, the indwelling medical device is a central venous catheter (“CVC”), a peripherally inserted central catheter (“PICC”), a midline catheter, a peripheral intravenous catheter (“PIVC”), or an acute dialysis catheter.

[0015] Also disclosed herein is a method of an infection-sensing medical system. The method includes, in some embodiments, an electrical signal-generating operation, a data- generating operation, a chemical signature-generating operation, and a microbial infectiondetermining operation. The electrical signal-generating operation includes generating electrical signals by one or more chemical sensors of a chemical-sensor module in response to interactions with one or more VOCs associated with a patient. The data-generating operation includes generating chemical-sensor data from the electrical signals by a microcontrollerprocessor. Both the chemical-sensor module and the microcontroller processor are part of a microcontroller integrated into a portion of an indwelling medical device. The indwelling medical device includes an intracorporeal conduit percutaneously inserted into a blood vessel of the patient, one or more extracorporeal conduits fluidly connected to the intracorporeal conduit that remain outside a body of the patient, and a hub between a proximal portion of the intracorporeal conduit and one or more respective distal portions of the one-or-more extracorporeal conduits. The chemical signature-generating operation includes generating one or more observed chemical signatures from the chemical-sensor data by a computing-device processor of a dedicated computing device. The microbial infection-determining operation includes determining with the computing-device processor whether the patient has a microbial infection by comparison of the one-or-more observed chemical signatures to known chemical signatures for microbial infections.

[0016] In some embodiments, the portion of the indwelling medical device in which the microcontroller is integrated is the hub.

[0017] In some embodiments, the method further includes a communicating operation. The communicating operation includes wirelessly communicating the chemical-sensor data from a microcontroller communications module of the microcontroller to a computing-device communications module of the dedicated computing device.

[0018] In some embodiments, the communicating operation includes wirelessly communicating the chemical-sensor data from the microcontroller communications module to the computing-device communications module over any communication protocol selected from wireless fidelity (“WiFi”), Bluetooth®, near-field communication (“NFC”), and Zigbee® communication protocols.

[0019] In some embodiments, the method further includes a data-storing operation. The data-storing operation includes storing the chemical-sensor data in memory of the microcontroller over time. The one-or-more observed chemical signatures generated by the computing-device processor in the chemical signature-generating operation includes a plurality of time-dependent observed chemical signatures in accordance with the chemical-sensor data stored in the memory over time during the data-storing operation.

[0020] In some embodiments, the method further includes a patient conditiondetermining operation. The patient condition-determining operation includes determining anychanges with respect to patient condition over time. The one-or-more observed chemical signatures are at least semi-quantitative with respect to one or more constituent VOCs thereof. The plurality of time-dependent observed chemical signatures thereby indicate semi- quantitative changes in the one-or-more constituent VOCs over time for the patient conditiondetermining operation.

[0021] In some embodiments, the method further includes a VOC-permeating operation. The VOC-permeating operation includes selectively allowing the one-or-more VOCs through a VOC-permeable membrane over water vapor. The indwelling medical device further includes the VOC-permeable membrane over the chemical-sensor module.

[0022] In some embodiments, the one-or-more VOCs are selected from indole, methanol, 1 -undecene, ethyl acetate, 2,4-dimethyl-l -heptane, 2-butanone, benzaldehyde, dimethylcyclohexanol, isovaleric acid, 2-pentanol, 4-methyl-quinazoline, and 2-methyl- butanal.

[0023] In some embodiments, the known chemical signatures for microbial infections are selected from a Staphylococcus aureus chemical signature including some combination of benzaldehyde, isovaleric acid, and 2-methyl-butanal; a Pseudomonas aeruginosa chemical signature including some combination of 1 -undecene, 2,4-dimethyl-l -heptane, 2-butanone, 2- pentanol, and 4-methyl-quinazoline; an Escherichia coli chemical signature including some combination of indole, methanol, ethyl acetate, and 2-pentanol; a Clostridium sporogenes chemical signature including some combination of indole, methanol, ethyl acetate, and 2- pentanol; and a Candida albicans chemical signature including some combination of methanol and dimethyl cyclohexanol.

[0024] In some embodiments, the method further includes a water-permeating operation. The water-permeating operation includes selectively allowing water vapor through a water vapor-permeable membrane over the one-or-more VOCs. The medical system further includes a wound dressing sized to cover an insertion site, any portion of the intracorporeal conduit of the indwelling medical device extending from the insertion site, and the hub of the indwelling medical device. The wound dressing includes a water vapor-permeable membrane.

[0025] In some embodiments, the indwelling medical device is a CVC, a PICC, a midline catheter, a PIVC, or an acute dialysis catheter.

[0026] Disclosed herein is a disease-sensing medical system including, in some embodiments, a breathalyzer and a dedicated computing device. The breathalyzer includes a breath-receiving tube configured to receive breath of a patient and a microcontroller integrated into a portion of the breathalyzer. The microcontroller includes a chemical-sensor module and a microcontroller processor. The chemical-sensor module includes one or more chemical sensors configured to generate electrical signals in response to interactions with one or more volatile organic chemicals (“VOCs”) associated with the patient. The microcontroller processor is configured to generate chemical-sensor data from the electrical signals. The dedicated computing device includes a computing-device processor configured to generate one or more observed chemical signatures from the chemical-sensor data. In addition, the computing-device processor is configured to determine whether the patient has a disease by comparison of the one-or-more observed chemical signatures to known chemical signatures for diseases.

[0027] In some embodiments, the one-or-more VOCs are selected from acetic acid, ethyl-cyclopropane, 2-ethyl-l -hexanol, acetone, and isopropanol.

[0028] In some embodiments, the known chemical signatures for diseases are selected from a tuberculosis chemical signature including some combination of acetic acid, ethyl- cyclopropane, and 2-ethyl-l -hexanol; and a diabetic ketoacidosis chemical signature including some combination of acetone and isopropanol.

[0029] In some embodiments, the breathalyzer and the dedicated computing device are integrated into a single disease-sensing medical device coextensive with the disease-sensing medical system.

[0030] These and other features of the concepts provided herein will become more apparent to those of skill in the art in view of the accompanying drawings and following description, which describe particular embodiments of such concepts in greater detail.BRIEF DESCRIPTION OF DRAWINGS

[0031] FIG. 1 illustrates an infection-sensing medical system including an indwelling medical device and a dedicated computing device in use on a patient in accordance with some embodiments.

[0032] FIG. 2 illustrates a detailed view of the indwelling medical device placed within the patient with a wound dressing thereover in accordance with some embodiments.

[0033] FIG. 3 illustrates the indwelling medical device in accordance with some embodiments.

[0034] FIG. 4 illustrates a detailed view of the indwelling medical device including a microcontroller integrated into a portion of the indwelling medical device in accordance with some embodiments.

[0035] FIG. 5 provides a schematic illustrating a VOC-permeable membrane over a sensor module of the microcontroller and a water vapor-permeable membrane of the wound dressing over the VOC-permeable membrane in accordance with some embodiments.

[0036] FIG. 6 provides a block diagram illustrating the microcontroller of the indwelling medical device in accordance with some embodiments.

[0037] FIG. 7 provides a block diagram illustrating the dedicated computing device in accordance with some embodiments.

[0038] FIG. 8 provides an observed chemical signature superimposed over a known chemical signature in accordance with some embodiments.

[0039] FIG. 9 provides a principal component analysis (“PCA”) for samples of fluids containing Candida albicans and control fluids without Candida albicans.

[0040] FIG. 10A provides a PCA for a sample of fluid containing Escherichia coli at a relatively lower level and a control fluid without Escherichia coli.

[0041] FIG. 10B provides a PCA for a sample of fluid containing Escherichia coli at a relatively higher level and a control fluid without Escherichia coli.

[0042] FIG. 11 illustrates a disease-sensing medical system in accordance with some embodiments.DESCRIPTION

[0043] Before some particular embodiments are disclosed in greater detail, it should be understood that the particular embodiments disclosed herein do not limit the scope of the concepts provided herein. It should also be understood that a particular embodiment disclosed herein can have features that can be readily separated from the particular embodiment andoptionally combined with or substituted for features of any of a number of other embodiments disclosed herein.

[0044] Regarding terms used herein, it should also be understood the terms are for the purpose of describing some particular embodiments, and the terms do not limit the scope of the concepts provided herein. Ordinal numbers (e.g., first, second, third, etc.) are generally used to distinguish or identify different features or steps in a group of features or steps, and do not supply a serial or numerical limitation. For example, “first,” “second,” and “third” features or steps need not necessarily appear in that order, and the particular embodiments including such features or steps need not necessarily be limited to the three features or steps. In addition, any of the foregoing features or steps can, in turn, further include one or more features or steps unless indicated otherwise. Labels such as “left,” “right,” “top,” “bottom,” “front,” “back,” and the like are used for convenience and are not intended to imply, for example, any particular fixed location, orientation, or direction. Instead, such labels are used to reflect, for example, relative location, orientation, or directions. Singular forms of “a,” “an,” and “the” include plural references unless the context clearly dictates otherwise.

[0045] “Proximal” is used to indicate a portion, section, piece, element, or the like of a medical device intended to be near or relatively nearer to a clinician when the medical device is used on a patient. For example, a “proximal portion” or “proximal section” of the medical device includes a portion or section of the medical device intended to be near the clinician when the medical device is used on the patient. Likewise, a “proximal length” of the medical device includes a length of the medical device intended to be near the clinician when the medical device is used on the patient. A “proximal end” of the medical device is an end of the medical device intended to be near the clinician when the medical device is used on the patient. The proximal portion, the proximal section, or the proximal length of the medical device need not include the proximal end of the medical device. Indeed, the proximal portion, the proximal section, or the proximal length of the medical device can be short of the proximal end of the medical device. However, the proximal portion, the proximal section, or the proximal length of the medical device can include the proximal end of the medical device. Should context not suggest the proximal portion, the proximal section, or the proximal length of the medical device includes the proximal end of the medical device, or if it is deemed expedient in the following description, “proximal portion,” “proximal section,” or “proximal length” can be modified to indicate such a portion, section, or length includes an end portion, an end section, or an endlength of the medical device for a “proximal end portion,” a “proximal end section,” or a “proximal end length” of the medical device, respectively.

[0046] “Distal” is used to indicate a portion, section, piece, element, or the like of a medical device intended to be near, relatively nearer, or even in a patient when the medical device is used on the patient. For example, a “distal portion” or “distal section” of the medical device includes a portion or section of the medical device intended to be near, relatively nearer, or even in the patient when the medical device is used on the patient. Likewise, a “distal length” of the medical device includes a length of the medical device intended to be near, relatively nearer, or even in the patient when the medical device is used on the patient. A “distal end” of the medical device is an end of the medical device intended to be near, relatively nearer, or even in the patient when the medical device is used on the patient. The distal portion, the distal section, or the distal length of the medical device need not include the distal end of the medical device. Indeed, the distal portion, the distal section, or the distal length of the medical device can be short of the distal end of the medical device. However, the distal portion, the distal section, or the distal length of the medical device can include the distal end of the medical device. Should context not suggest the distal portion, the distal section, or the distal length of the medical device includes the distal end of the medical device, or if it is deemed expedient in the following description, “distal portion,” “distal section,” or “distal length” can be modified to indicate such a portion, section, or length includes an end portion, an end section, or an end length of the medical device for a “distal end portion,” a “distal end section,” or a “distal end length” of the medical device, respectively.

[0047] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by those of ordinary skill in the art.Medical systems

[0048] FIG. 1 illustrates an infection-sensing medical system 100 including an indwelling medical device 102 and a dedicated computing device 104 in use on a patient in accordance with some embodiments. As shown, the infection-sensing medical system 100 can include the indwelling medical device 102 and the dedicated computing device 104. However, it should be understood that the infection-sensing medical system 100 is not limited to the indwelling medical device 102 and the dedicated computing device 104. The indwelling medical device 102 can alternatively be any medical device configured to interface with a patient and collect the one-or-more VOCs therefrom. For example, the indwelling medicaldevice 102 can alternatively be a breathalyzer 170 as shown in FIG. 11, which breathalyzer 170 can be similarly configured with the microcontroller 118, the VOC-permeable membrane 120, and the like but modified to collect the one-or-more VOCs from breath blown into a breath-receiving tube 172 for determining whether the patient has tuberculosis, coronavirus disease 2019 (“COVID-19”), lung cancer, diabetic ketoacidosis, or the like.

[0049] The dedicated computing device 104 can alternatively be any general -purpose computing device (e.g., desktop computer, smartphone, etc.) configured like that set forth below with respect to the dedicated computing device 104 to generate the one-or-more observed chemical signatures and determine whether the patient has a microbial infection or the aforenamed tuberculosis, COVID-19, lung cancer, or diabetic ketoacidosis therefrom. Further, the medical device including the indwelling medical device 102 and the computing device including the dedicated computing device 104 can be separate, as shown in FIG. 1, or integrated into a single infection-sensing medical device substantially coextensive with the infection-sensing medical system 100 or, more broadly, a single disease-sensing medical device substantially coextensive with a disease-sensing medical system such as the breathalyzer 170 shown in FIG. 11. Notably, in such embodiments, the microcontroller 118 and the dedicated computing device 104 can be integrated into a single unit such as a single printed circuit board assembly (“PCB A”) configured to function as set forth below.

[0050] FIG. 2 illustrates a detailed view of the indwelling medical device 102 placed within the patient with a wound dressing 106 thereover in accordance with some embodiments. As shown, the infection-sensing medical system 100 can further include the wound dressing 106 sized to cover an insertion site, any portion of the intracorporeal conduit 110 of the indwelling medical device 102 extending from the insertion site, and the hub 114 of the indwelling medical device 102.

[0051] Notably, the wound dressing 106 can include a water vapor-permeable membrane 108 configured to selectively allow water vapor therethrough over the one-or-more VOCs. Indeed, the water vapor-permeable membrane 108 can include a porous membrane such as a reverse-osmosis membrane or a two-dimensional (“2D”) or three-dimensional (“3D”) covalent-organic-framework (“COF”) membrane configured to selectively allow water vapor therethrough over the one-or-more VOCs. Further, instead of the indwelling medical device 102 being configured as set forth herein, the wound dressing 106 can be similarly configured with the microcontroller 118, the VOC-permeable membrane 120, and the like for use with anexisting indwelling medical device such as a CVC, a PICC, a midline catheter, a PIVC, or an acute dialysis catheter to collect the one-or-more VOCs. That said, such a wound dressing 106 can also be used with the indwelling medical device 102 for failproof redundancy or confirmation of one or the other. Further yet, it should be understood catheter-stabilization devices, hospital bags, wearable drug-deliver patches, wrist bands, smart watches, or the like can be similarly configured with the microcontroller 118, the VOC-permeable membrane 120, and the like for collecting the one-or-more VOCs.

[0052] FIG. 3 illustrates the indwelling medical device 102 in accordance with some embodiments. As shown, the indwelling medical device 102 can include an intracorporeal conduit 110, one or more extracorporeal conduits 112 fluidly connected to the intracorporeal conduit 110, a hub 114 between a proximal portion of the intracorporeal conduit 110 and one or more respective distal portions of the one-or-more extracorporeal conduits 112, and one or more respective connectors 116 of the one-or-more extracorporeal conduits 112. Notably, the intracorporeal conduit 110 is configured to be percutaneously inserted into a blood vessel of a patient, and the one-or-more extracorporeal conduits 112 are configured to remain outside a body of the patient. Such an indwelling medical device 102 can include, but is not limited to, a catheter such as a CVC, a PICC, a midline catheter, a PIVC, or an acute dialysis catheter, wherein the intracorporeal conduit 110 is a catheter tube of the catheter, and the one-or-more extracorporeal conduits 112 are the extension legs of the catheter.

[0053] FIG. 4 illustrates a detailed view of the indwelling medical device 102 including a microcontroller 118 integrated into a portion of the indwelling medical device 102 in accordance with some embodiments. FIG. 6 provides a block diagram illustrating the microcontroller 118 of the indwelling medical device 102 in accordance with some embodiments. As shown, the microcontroller 118 can be integrated into a portion of the indwelling medical device 102. As shown, the portion of the indwelling medical in which the microcontroller 118 is integrated can be the hub 114 such as a top of the hub 114, a side of the hub 114, or both the top and the side of the hub 114.

[0054] In at least the latter embodiment, the components of the microcontroller 118 can be split between the top and the side of the hub 114, for example, with the chemical-sensor module 122 in the side of the hub 114 closest to the insertion site operably coupled to a remainder of the microcontroller 118 in the top of the hub 114 with the power supply 132 (e.g., the internal power supply). While not shown, the portion of the indwelling medical in whichthe microcontroller 118 is integrated can alternatively be a connector of the one-or-more connectors 116. Alternatively, instead of the indwelling medical device 102 being configured as set forth herein, a needless connector similarly configured with the microcontroller 118, the VOC-permeable membrane 120, and the like can be connected to one or more connectors of an existing indwelling medical device such as a CVC, a PICC, a midline catheter, a PIVC, or an acute dialysis catheter to collect the one-or-more VOCs. While farther from the insertion site, an advantage of the microcontroller 118 being integrated in a connector of the one-or- more connectors 116 or the foregoing needless connector includes convenience when coupling to the dedicated computing device 104 in wired embodiments.

[0055] FIG. 5 provides a schematic illustrating a VOC-permeable membrane 120 over the sensor module of the microcontroller 118 and the water vapor-permeable membrane 108 of the wound dressing 106 over the VOC-permeable membrane 120 in accordance with some embodiments. As shown, the indwelling medical device 102 can include the VOC-permeable membrane 120 over at least the chemical-sensor module 122. Indeed, the VOC-permeable membrane 120 can be further over an entirety of the microcontroller 118 as shown in FIG. 4, which can advantageously increase a volume of VOC-collecting headspace over the chemicalsensor module 122. The VOC-permeable membrane 120 can be configured to selectively allow the one-or-more VOCs therethrough over water vapor, any water condensate, any sensorfouling components of wound exudate, or the like. Additionally or alternatively, the VOC- permeable membrane 120 can be hydrophobic, which limits water vapor or condensate interactions therewith. Together with the water vapor-permeable membrane 108 of the wound dressing 106, which, as set forth above, can be configured to selectively allow water vapor therethrough over the one-or-more VOCs, the VOC-permeable membrane 120 can facilitate separation and concentration of the one-or-more VOCs in the VOC-collecting headspace over the chemical sensor module.

[0056] The one-or-more VOCs for which the VOC-permeable membrane 120 can be configured to selectively allow therethrough for interaction with the one-or-more chemical sensors 134 of the chemical-sensor module 122 are selected from at least indole, methanol, 1- undecene, ethyl acetate, 2,4-dimethyl-l -heptane, 2-butanone, benzaldehyde, dimethylcyclohexanol (e.g., 2,2-dimethylcyclohexanol, 2,6-dimethylcyclohexanol, or 4,4- dimethylcyclohexanol), isovaleric acid, 2-pentanol, 4-methyl-quinazoline, and 2-methyl- butanal. Indeed, as set forth in Table 1 below, some combination of benzaldehyde, isovalericacid, and 2-methyl-butanal can indicate a microbial infection with Staphylococcus aureus,' some combination of 1 -undecene, 2,4-dimethyl-l -heptane, 2-butanone, 2-pentanol, and 4- methyl-quinazoline can indicate a microbial infection with Pseudomonas aeruginosa, some combination of indole, methanol, ethyl acetate, and 2-pentanol can indicate a microbial infection with Escherichia coli some combination of indole, methanol, ethyl acetate, and 2- pentanol can indicate a microbial infection with Clostridium sporogenes,' and some combination of methanol and dimethyl cyclohexanol can indicate a microbial infection with Candida albicans. However, the VOC-permeable membrane 120 need not be limited to selectively allowing one or more of the aforenamed VOCs therethrough for interaction with the one-or-more chemical sensors 134 of the sensor module. Indeed, the VOC-permeable membrane 120 can be configured to selectively allow therethrough one or more other VOCs indicative of a microbial infection with Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Clostridium sporogenes, Candida albicans, or even another microorganism such as a carbapenem-resistant bacterium of family Enterob acteriaceae, an extended- spectrum P-lactamase (“ESBL”)-producing bacterium of Enterobacteriaceae, a vancomycin-resistant bacterium of Enterococcus, a multidrug-resistant bacterium of Acinetobacter, a multidrugresistant bacterium of genus Klebsiella, the one-or-more other VOCs optionally in combination with one or more of the aforenamed VOCs.Table 1. Microorganisms indicated by select biomarkers of off-gassed VOC metabolites

[0057] Notwithstanding the foregoing, it should be understood the one-or-more VOCs for which the VOC-permeable membrane 120 can be configured to selectively allow therethrough for interaction with the one-or-more chemical sensors 134 of the sensor module are selected from at least acetic acid, ethyl-cyclopropane, and 2-ethyl-l -hexanol, which are expired from patients suffering from tuberculosis, and acetone and isopropanol, which are expired from patients suffering from diabetic ketoacidosis, in embodiments of the medical device configured as the breathalyzer.

[0058] FIG. 6 provides a block diagram illustrating the microcontroller 118 of the indwelling medical device 102 in accordance with some embodiments. As shown, the microcontroller 118 can include components selected from a chemical-sensor module 122, a sensor interface 124, a processor 126, secondary memory 128, a communications module 130, and a power supply 132 such as an internal power supply (e.g., a battery). The chemical-sensor module 122 can include one or more chemical sensors 134 configured to generate electrical signals in response to interactions with one or more VOCs associated with the patient or, more specifically, microorganisms of the patient.

[0059] The one-or-more chemical sensors 134 can include, but are not limited to those having so-called receptors selected from metals, metal oxides, organic molecules ranging from small-molecule organic compounds to polymers such as amino acids, peptides, polypeptides, proteins, nucleosides, nucleotides, oligonucleotides, monosaccharides, disaccharides, oligosaccharides, polysaccharides, or phospholipids, and allotropes of carbon such as graphene and various fullerenes, some of which are disclosed in US 2020 / 0256793, which application is incorporated herein in its entirety. Each sensor of the one-or-more chemical sensors 134 can respond differently to interactions with the one-or-more VOCs, thereby providing the one-or- more observed chemical signatures, which, like fingerprints, are unique, allowing comparison of the one-or-more observed chemical signatures to known chemical signatures for determining microbial infections. Notably, the chemical-sensor module 122 or a separate correction-sensor module 136 of the microcontroller 118 can include one or more additional sensors selected from at least a temperature sensor 138 and a humidity sensor 140 for correcting the following chemical-sensor data, if needed, with respect to temperature and humidity. The sensor interface 124 can include a signal conditioner 142 configured to standardize the electrical signals through voltage or current limiting, anti-aliasing filtering, or the like, particularly if the electrical signals are generated by a plurality of the chemical sensors 134, each of which chemical sensors 134can have a different configuration for a different interaction with a same VOC of the one-or- more VOCs.

[0060] In addition, the sensor interface 124 can include an amplifier 144 configured to amplify the electrical signals and, thereby, increase their signal -to-noise ratio. The processor 126 can include an analog-to-digital converter (“ADC”) 146 configured to convert the electrical signals from analog to digital, a digital-signal processor 148 (“DSP”) configured to generate chemical-sensor data from the electrical signals, and primary memory 150 (e.g., cache memory, random-access memory [“RAM”], or both) configured to store in-use programs and data. While the primary memory 150 can be within the same package as a remainder of the processor 126 as alluded to in FIG. 6, at least the foregoing RAM can be distributed outside the package of the processor 126 but within that of the microcontroller 118 itself. The secondary memory 128 can be configured to store data such as the chemical-sensor data over time as well as programs including instructions, logic, algorithms, or some combination thereof for loading into the primary memory 150 for use by the processor 126. The communications module 130 can be configured for wireless communications of at least the chemical-sensor data over any communication protocol selected from WiFi, Bluetooth®, NFC, and Zigbee® communication protocols with the communications module 156 of the dedicated computing device 104. Notably, the communications module 130 can be alternatively or additionally configured for wired communications of at least the chemical-sensor data over any serial or parallel communication protocol.

[0061] Notwithstanding the foregoing, it should be understood the foregoing microcontroller 118 is described with respect to the one-or-more chemical sensors 134 of the chemical-sensor module 122 being one or more analog chemical sensors, the electrical signals generated thereby being analog electrical signals. Should the one-or-more chemical sensors 134 of the chemical-sensor module 122 instead be one or more digital chemical sensors, which can include digitizing optical interferometers or built-in signal-processing capabilities like that set for the above, the microcontroller 118 can be modified accordingly to process digital electrical signals or the chemical-sensor data therefrom.

[0062] FIG. 7 provides a block diagram illustrating the dedicated computing device 104 in accordance with some embodiments. As shown, the dedicated computing device 104 can include components selected from a processor 152, secondary memory 154, a communications module 156, and a power supply 158 such as an internal power supply (e.g.,a battery) or an external power supply (e.g., utility power). Further, the dedicated computing device 104 can include one or more input devices 160 (e.g., a keyboard, a mouse, a touchscreen display screen, or the like) and one or more output devices 162 (e.g., the touchscreen display screen, a printer, or the like). The processor 152 can include a control unit 164, an arithmetic unit 166, and primary memory 168 (e.g., cache memory, RAM, or both), the primary memory 168 configured to store in-use programs and data.

[0063] While the primary memory 168 can be within the same package as a remainder of the processor 152 as alluded to in FIG. 7, at least the foregoing RAM can be distributed outside the package of the processor 152, for example, in its own package. The processor 152 can be configured to generate one or more observed chemical signatures from the chemicalsensor data generated by the processor 126 of the microcontroller 118. In addition, the processor 152 can be configured to determine whether the patient has a microbial infection by comparison of the one-or-more observed chemical signatures to known chemical signatures for microbial infections. Notably, the one-or-more observed chemical signatures generated by the processor 152 can include a plurality of time-dependent observed chemical signatures in accordance with the chemical-sensor data stored in at least the secondary memory 128 of the microcontroller 118 over time. The secondary memory 154 can be configured to store such time-dependent observed chemical signatures as well as other data and programs including instructions, logic, algorithms including machine-learning algorithms, artificial intelligence (“Al”) models, or some combination thereof for loading into the primary memory 168 for use by the processor 152 for generating the one-or-more observed chemical signatures from the chemical-sensor data and comparing them, for example, by statistical analysis, to the known chemical signatures for determining microbial infections.

[0064] FIG. 8 provides an observed chemical signature superimposed over a known chemical signature in accordance with some embodiments. As shown, the one-or-more observed chemical signatures generated by the processor 152 and the known chemical signatures can be displayed as superimposed radar charts on, for example, a display screen such as the foregoing touchscreen display screen if available as an output device of the one-or-more output devices 162.

[0065] A superimposed radar chart including constituent radar charts of the one-or- more observed chemical signatures and the known chemical signatures can, as shown, include a plurality of equiangular axes or the like against a plurality of concentric shapes such as circles,regular polygons, or the like. Each axis of the plurality of equiangular axes corresponds to a different sensor (e.g., sensor / / , sensor w+7, sensor n+2, etc.) of the plurality of chemical sensors 134, and each concentric shape of the plurality of concentric shapes from a smallest shape to a largest shape represents an increase in signal intensity. Radar charts such as that shown in FIG. 8 or alternatives thereto such as parallel-coordinates plots are useful to clinicians for analyzing a presence, an absence, or an intensity of one or more constituent VOCs in the one-or-more observed chemical signatures, optionally, over time. However, it should be understood that the dedicated computing device 104 need not superimpose and display any radar charts for the processor 152, itself, to determine whether the patient has a microbial infection. Indeed, the one-or-more observed chemical signatures and the known chemical signatures can exist as data structures in at least the secondary memory 154 of the dedicated computing device 104 for comparison of the one-or-more observed chemical signatures to the known chemical signatures for determining microbial infections.

[0066] The known chemical signatures for microbial infections, which can be updated over time, as needed, can be selected from a Staphylococcus aureus chemical signature including some combination of benzaldehyde, isovaleric acid, and 2-methyl-butanal; a Pseudomonas aeruginosa chemical signature including some combination of 1 -undecene, 2,4- dimethyl-1 -heptane, 2-butanone, 2-pentanol, and 4-methyl-quinazoline; an Escherichia coli chemical signature including some combination of indole, methanol, ethyl acetate, and 2- pentanol; a Clostridium sporogenes chemical signature including some combination of indole, methanol, ethyl acetate, and 2-pentanol; and a Candida albicans chemical signature including some combination of methanol and dimethyl cyclohexanol.

[0067] Notably, the one-or-more observed chemical signatures can be at least semi- quantitative down to at least parts-per-million (“ppm”) concentrations for the one-or-more constituent VOCs thereof, which can require a correction factor predetermined by, for example, a photoionization detector, for each VOC of the one-or-more VOCs. As such, the plurality of time-dependent observed chemical signatures can indicate semi-quantitative changes in the one-or-more constituent VOCs of the time-dependent observed chemical signatures over time and, thus, any changes with respect to patient condition over time. In an example, an increase in the one-or-more constituent VOCs of the time-dependent observed chemical signatures can indicate an increasing rate of microbial infection and, thus, a worsening patient condition over time. In another example, a decrease in the one-or-more constituent VOCs of the time-dependent observed chemical signatures can indicate a decreasing rate of microbial infection and, thus, a bettering patient condition over time. As such, the processor 152 can be accordingly configured to determine any changes with respect to the patient condition over time such as a worsening patient condition over time due to an increasing rate of microbial infection or a bettering patient condition over time due to a decreasing rate of microbial infection. Likewise, the processor 152 can be configured to determine no change with respect to the patient condition over time when there is neither an increasing rate of microbial infection nor a decreasing rate of microbial condition.Methods

[0068] Methods include methods of the infection-sensing medical system 100, itself, as well as methods of using the infection-sensing medical system 100.

[0069] A method of the infection-sensing medical system 100 can include one or more operations selected from a water-permeating operation, a VOC-permeating operation, an electrical signal-generating operation, a data-generating operation, a data-storing operation, a communicating operation, a chemical signature-generating operation, a microbial infectiondetermining operation, and a patient condition-determining operation.

[0070] The water-permeating operation can include selectively allowing water vapor through the water vapor-permeable membrane 108 of the wound dressing 106 over the one-or- more VOCs. As set forth above, the infection-sensing medical system 100 can include the wound dressing 106 sized to cover an insertion site, any portion of the intracorporeal conduit 110 of the indwelling medical device 102 extending from the insertion site, and the hub 114 of the indwelling medical device 102.

[0071] The VOC-permeating operation can include selectively allowing the one-or- more VOCs through the VOC-permeable membrane 120 over water vapor. As set forth above, the indwelling medical device 102 can include the VOC-permeable membrane 120 over at least the chemical-sensor module 122. Further, the one-or-more VOCs for which the VOC- permeable membrane 120 can be configured to selectively allow therethrough for interaction with the one-or-more chemical sensors 134 of the sensor module are selected from at least indole, methanol, 1 -undecene, ethyl acetate, 2,4-dimethyl-l -heptane, 2-butanone, benzaldehyde, dimethylcyclohexanol (e.g., 2,2-dimethylcyclohexanol, 2,6-dimethylcyclohexanol, or 4,4-dimethylcyclohexanol), isovaleric acid, 2-pentanol, 4-methyl- quinazoline, and 2-methyl-butanal.

[0072] The electrical signal-generating operation can include generating electrical signals by the one-or-more chemical sensors 134 of the chemical-sensor module 122 in response to the interactions with the one-or-more VOCs associated with a patient or, more specifically, microorganisms of the patient.

[0073] The data-generating operation can include generating the chemical-sensor data from the electrical signals by the processor 126. Both the chemical-sensor module 122 and the processor 126 are part of the microcontroller 118 integrated into the portion of the indwelling medical device 102 set forth above.

[0074] The data-storing operation can include storing the chemical-sensor data in the secondary memory 128 of the microcontroller 118 over time.

[0075] The communicating operation can include wirelessly communicating the chemical-sensor data from the communications module 130 of the microcontroller 118 to the communications module 156 of the dedicated computing device 104. Such a communicating operation can include wirelessly communicating the chemical-sensor data from the communications module 130 of the microcontroller 118 to the communications module 156 of the dedicated computing device 104 over any communication protocol selected from WiFi, Bluetooth®, NFC, and Zigbee® communication protocols.

[0076] The chemical signature-generating operation can include generating the one-or- more observed chemical signatures from the chemical-sensor data by the processor 152 of the dedicated computing device 104. The one-or-more observed chemical signatures generated by the processor 152 in the chemical signature-generating operation can include the plurality of time-dependent observed chemical signatures in accordance with the chemical-sensor data stored in the secondary memory 128 of the microcontroller 118 over time during the data- storing operation.

[0077] The microbial infection-determining operation can include determining with the processor 152 of the dedicated computing device 104 whether the patient has a microbial infection by comparison of the one-or-more observed chemical signatures to the known chemical signatures for microbial infections. As set forth above, the known chemical signaturesfor microbial infections can be selected from the Staphylococcus aureus chemical signature including some combination of benzaldehyde, isovaleric acid, and 2-methyl-butanal; the Pseudomonas aeruginosa chemical signature including some combination of 1 -undecene, 2,4- dimethyl-1 -heptane, 2-butanone, 2-pentanol, and 4-methyl-quinazoline; the Escherichia coli chemical signature including some combination of indole, methanol, ethyl acetate, and 2- pentanol; the Clostridium sporogenes chemical signature including some combination of indole, methanol, ethyl acetate, and 2-pentanol; and the Candida albicans chemical signature including some combination of methanol and dimethyl cyclohexanol.

[0078] The patient condition-determining operation can include determining any changes with respect to the patient condition over time. As set forth above, the one-or-more observed chemical signatures can be at least semi-quantitative with respect to the one-or-more constituent VOCs thereof. The plurality of time-dependent observed chemical signatures thereby indicate semi -quantitative changes in the one-or-more constituent VOCs over time for the patient condition-determining operation.

[0079] A method of using the infection-sensing medical system 100 can include one or more operations selected from a medical device-placing operation, which can include placing the indwelling medical device 102 in a blood vessel of a patient; a wound-dressing operation, which can include covering an insertion site, any portion of the intracorporeal conduit 110 of the indwelling medical device 102 extending from the insertion site, the hub 114 of the indwelling medical device 102, or a combination thereof with the wound dressing 106; a medical system-powering operation, which can include powering on the indwelling medical device 102, the dedicated computing device 104, or both the indwelling medical device 102 and the dedicated computing device 104 to instantiate one or more operations set forth above for the method of the infection-sensing medical system 100, optionally after observing one or more clinical criteria of systemic inflammatory response syndrome (e.g., body temperature > 100 °F, heart rate > 90 beats per minute, or respiratory rate > 20 breaths per minute), inflammation around the insertion site, or a combination thereof; and a reading operation, which can include a clinician reading output from the one-or-more output devices 162 of the dedicated computing device 104 regarding whether the patient has a microbial infection. The reading operation can be iteratively performed by the clinician for any changes with respect to the patient condition over time.

[0080] The infection-sensing medical system 100 and methods advantageously provide rapid and accurate results with respect to one or more VOC biomarkers for determining at least microbial infections and patient condition, which otherwise currently requires at least 24-48 hours of laboratory work. This facilitates microorganism-specific treatments with faster response times for such microbial infections, which improves patient outcomes.Examples

[0081] An experimental system was set up including the following: 1) HeptaValve Mini (Aryballe Technologies, Grenoble France) for switching between samples and controls without modifying a remainder of the experimental system; 2) Amplifier (Aryballe Technologies, Grenoble France), which includes a cartridge of Tenax® TA adsorbent (20 mg, 60-80 mesh) with hydrophobic behavior for concentrating VOCs by adsorption and subsequent desorption by flash heating; and 3) NeOse Advance (Aryballe Technologies, Grenoble France) for digital olfaction. The NeOse Advance includes a pump to manage airflow; a core sensor including an array of 42 peptide-based sensors immobilized on Mach-Zehnder Interferometers for digitizing interactions with the VOCs; humidity and temperature sensors for normalizing the electrical signals; and a photoionization detector for determining correction factors for the semi-quantification of the VOCs.

[0082] Samples of fluids containing Candida albicans or Escherichia coli were tested with the experimental system against control fluids not including such microorganisms, and results showed the experimental system differentiates the samples containing the microorganisms from the control fluids. In an example, FIG. 9 shows a PCA for two samples of fluids containing Candida albicans, namely “CANDIDAFLUIDA” and “CANDIDAFLUIDB,” and control fluids, namely “FLUIDA” and “FLUIDB,” without Candida albicans, thereby demonstrating differentiation of the foregoing fluids by the experimental setup. In another example, FIG. 10A shows a PCA for a sample of fluid containing Escherichia coli at a relatively lower level of 320 colony forming units (“CFU”), namely “ECOLI1,” and control fluid A, namely “FLUIDA,” without Escherichia coli, thereby demonstrating differentiation of the foregoing fluids by the experimental setup. Further, FIG. 10B shows a PCA for a sample of fluid containing Escherichia coli at a relatively higher level of 2700 CFUs, namely “ECOLI2,” and control fluid A, namely “FLUIDA,” without Escherichia coli, thereby demonstrating differentiation of the foregoing fluids by the experimental setup.

[0083] While some particular embodiments have been disclosed herein, and while the particular embodiments have been disclosed in some detail, it is not the intention for the particular embodiments to limit the scope of the concepts provided herein. Additional adaptations or modifications can appear to those of ordinary skill in the art, and, in broader aspects, these adaptations or modifications are encompassed as well. Accordingly, departures may be made from the particular embodiments disclosed herein without departing from the scope of the concepts provided herein.

Claims

CLAIMSWhat is claimed is:

1. An infection-sensing medical system, comprising: an indwelling medical device, including: an intracorporeal conduit configured to be percutaneously inserted into a blood vessel of a patient; one or more extracorporeal conduits fluidly connected to the intracorporeal conduit, the one-or-more extracorporeal conduits configured to remain outside a body of the patient; a hub between a proximal portion of the intracorporeal conduit and one or more respective distal portions of the one-or-more extracorporeal conduits; and a microcontroller integrated into a portion of the indwelling medical device, the microcontroller including: a chemical-sensor module including one or more chemical sensors configured to generate electrical signals in response to interactions with one or more volatile organic chemicals (“VOCs”) associated with the patient; and a microcontroller processor configured to generate chemical-sensor data from the electrical signals; and a dedicated computing device including a computing-device processor configured to: generate one or more observed chemical signatures from the chemicalsensor data; and determine whether the patient has a microbial infection by comparison of the one-or-more observed chemical signatures to known chemical signatures for microbial infections.

2. The infection-sensing medical system of claim 1, wherein the indwelling medical device further includes one or more respective connectors of the one-or-more extracorporeal conduits, the portion of the indwelling medical device in which the microcontroller is integrated being a connector of the one-or-more connectors.

3. The infection-sensing medical system of claim 1, wherein the portion of the indwelling medical device in which the microcontroller is integrated is the hub.

4. The infection-sensing medical system of any of the preceding claims, wherein the microcontroller further includes a microcontroller communications module configured for wireless communications with a computing-device communications module of the dedicated computing device, the wireless communications including at least the chemical-sensor data.

5. The infection-sensing medical system of any of the preceding claims, wherein the microcontroller further includes memory configured to store the chemical-sensor data over time, the one-or-more observed chemical signatures generated by the computing-device processor including a plurality of time-dependent observed chemical signatures in accordance with the chemical-sensor data stored in the memory over time.

6. The infection-sensing medical system of claim 5, wherein the one-or-more observed chemical signatures are at least semi-quantitative with respect to one or more constituent VOCs thereof, the plurality of time-dependent observed chemical signatures thereby indicating semi-quantitative changes in the one-or-more constituent VOCs over time and, thus, any changes with respect to patient condition over time.

7. The infection-sensing medical system of any of the preceding claims, wherein the indwelling medical device further includes a VOC-permeable membrane over the chemicalsensor module, the VOC-permeable membrane configured to selectively allow the one-or-more VOCs therethrough over water vapor.

8. The infection-sensing medical system of any of the preceding claims, wherein the one-or-more VOCs are selected from indole, methanol, 1 -undecene, ethyl acetate, 2,4- dimethyl-1 -heptane, 2-butanone, benzaldehyde, dimethylcyclohexanol, isovaleric acid, 2- pentanol, 4-methyl-quinazoline, and 2-methyl-butanal.

9. The infection-sensing medical system of any of the preceding claims, wherein the known chemical signatures for microbial infections are selected from a Staphylococcus aureus chemical signature including some combination of benzaldehyde, isovaleric acid, and 2-methyl-butanal; a Pseudomonas aeruginosa chemical signature including some combination of 1 -undecene, 2,4-dimethyl-l -heptane, 2-butanone, 2-pentanol, and 4-methyl-quinazoline; an Escherichia coli chemical signature including some combination of indole, methanol, ethylacetate, and 2-pentanol; a Clostridium sporogenes chemical signature including some combination of indole, methanol, ethyl acetate, and 2-pentanol; and a Candida albicans chemical signature including some combination of methanol and dimethyl cyclohexanol.

10. The infection-sensing medical system of any of the preceding claims, further comprising a wound dressing sized to cover an insertion site, any portion of the intracorporeal conduit of the indwelling medical device extending from the insertion site, and the hub of the indwelling medical device, the wound dressing including a water vapor-permeable membrane configured to selectively allow water vapor therethrough over the one-or-more VOCs.

11. The infection-sensing medical system of any of the preceding claims, wherein the indwelling medical device is a central venous catheter (“CVC”), a peripherally inserted central catheter (“PICC”), a midline catheter, a peripheral intravenous catheter (“PIVC”), or an acute dialysis catheter.

12. A method of an infection-sensing medical system, comprising: generating electrical signals by one or more chemical sensors of a chemicalsensor module in response to interactions with one or more volatile organic chemicals (“VOCs”) associated with a patient; generating chemical-sensor data from the electrical signals by a microcontroller processor, both the chemical-sensor module and the microcontroller processor part of a microcontroller integrated into a portion of an indwelling medical device including: an intracorporeal conduit percutaneously inserted into a blood vessel of the patient; one or more extracorporeal conduits fluidly connected to the intracorporeal conduit, the one or more extracorporeal conduits remaining outside a body of the patient; and a hub between a proximal portion of the intracorporeal conduit and one or more respective distal portions of the one-or-more extracorporeal conduits; generating one or more observed chemical signatures from the chemical-sensor data by a computing-device processor of a dedicated computing device; anddetermining with the computing-device processor whether the patient has a microbial infection by comparison of the one-or-more observed chemical signatures to known chemical signatures for microbial infections.

13. The method of claim 12, wherein the portion of the indwelling medical device in which the microcontroller is integrated is the hub.

14. The method of either claim 12 or claim 13, further comprising wirelessly communicating the chemical-sensor data from a microcontroller communications module of the microcontroller to a computing-device communications module of the dedicated computing device.

15. The method of claim 12, wherein the wirelessly communicating of the chemical-sensor data from the microcontroller communications module to the computingdevice communications module includes wirelessly communicating over any communication protocol selected from wireless fidelity (“WiFi”), Bluetooth®, near-field communication (“NFC”), and Zigbee® communication protocols.

16. The method of any of claims 12-15, further comprising storing the chemicalsensor data in memory of the microcontroller over time, the one-or-more observed chemical signatures generated by the computing-device processor including a plurality of timedependent observed chemical signatures in accordance with the chemical-sensor data stored in the memory over time.

17. The method of claim 16, further comprising determining any changes with respect to patient condition over time, the one-or-more observed chemical signatures being at least semi-quantitative with respect to one or more constituent VOCs thereof, the plurality of time-dependent observed chemical signatures thereby indicating semi -quantitative changes in the one-or-more constituent VOCs over time for the determining of any changes with respect to the patient condition over time.

18. The method of any of claims 12-17, further comprising selectively allowing the one-or-more VOCs through a VOC-permeable membrane over water vapor, the indwelling medical device further including the VOC-permeable membrane over the chemical-sensor module.

19. The method of any of claims 12-18, wherein the one-or-more VOCs are selected from indole, methanol, 1 -undecene, ethyl acetate, 2,4-dimethyl-l -heptane, 2-butanone, benzaldehyde, dimethylcyclohexanol, isovaleric acid, 2-pentanol, 4-methyl-quinazoline, and 2-methyl-butanal.

20. The method of any of claims 12-19, wherein the known chemical signatures for microbial infections are selected from a Staphylococcus aureus chemical signature including some combination of benzaldehyde, isovaleric acid, and 2-methyl-butanal; a Pseudomonas aeruginosa chemical signature including some combination of 1 -undecene, 2,4-dimethyl-l- heptane, 2-butanone, 2-pentanol, and 4-methyl-quinazoline; an Escherichia coli chemical signature including some combination of indole, methanol, ethyl acetate, and 2-pentanol; a Clostridium sporogenes chemical signature including some combination of indole, methanol, ethyl acetate, and 2-pentanol; and a Candida albicans chemical signature including some combination of methanol and dimethyl cyclohexanol.

21. The method of any of claims 12-20, further comprising selectively allowing water vapor through a water vapor-permeable membrane over the one-or-more VOCs, the medical system further including a wound dressing sized to cover an insertion site, any portion of the intracorporeal conduit of the indwelling medical device extending from the insertion site, and the hub of the indwelling medical device, the wound dressing including water vapor- permeable membrane.

22. The method of any of claims 12-21, wherein the indwelling medical device is a central venous catheter (“CVC”), a peripherally inserted central catheter (“PICC”), a midline catheter, a peripheral intravenous catheter (“PIVC”), or an acute dialysis catheter.

23. A disease-sensing medical system, comprising: a breathalyzer, including: a breath-receiving tube configured to receive breath of a patient; and a microcontroller integrated into a portion of the breathalyzer, the microcontroller including: a chemical-sensor module including one or more chemical sensors configured to generate electrical signals in response to interactions with one or more volatile organic chemicals (“VOCs”) associated with the patient; anda microcontroller processor configured to generate chemical-sensor data from the electrical signals; and a dedicated computing device including a computing-device processor configured to: generate one or more observed chemical signatures from the chemicalsensor data; and determine whether the patient has a disease by comparison of the one-or- more observed chemical signatures to known chemical signatures for diseases.

24. The disease-sensing medical system of claim 23, wherein the one-or-more VOCs are selected from acetic acid, ethyl-cyclopropane, 2-ethyl-l -hexanol, acetone, and isopropanol.

25. The disease-sensing medical system of either claim 23 or 24, wherein the known chemical signatures for diseases are selected from a tuberculosis chemical signature including some combination of acetic acid, ethyl-cyclopropane, and 2-ethyl-l-hexanol; and a diabetic ketoacidosis chemical signature including some combination of acetone and isopropanol.

26. The disease-sensing medical system of any of claims 23-25, wherein the breathalyzer and the dedicated computing device are integrated into a single disease-sensing medical device coextensive with the disease-sensing medical system.

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