Apparatus, system, and method for measuring solution characteristics of a sample using a multi-layer active sensor

Abstract

Various devices, systems, and methods are disclosed for measuring solution properties of a sample containing a microorganism. In one embodiment, a sensor device is disclosed that includes a sample chamber having a chamber sidewall surrounding a chamber cavity configured to receive the sample, a reference sensor including a transport element for transporting the sample to a reference electrode material, and an active sensor formed from a substrate partially covered by an active electrode layer. The active sensor can be coupled to at least a portion of the chamber sidewall at a window opening formed along the chamber sidewall. The active sensor can be positioned such that the active electrode layer faces the chamber cavity, allowing a sample in the chamber cavity to fluidly contact the active electrode layer through at least a portion of the chamber sidewall surrounding the window opening.

Description

Technical Field

[0001] The present disclosure generally relates to a diagnostic device for measuring solution characteristics of a sample. More specifically, the present disclosure relates to an apparatus, system, and method for measuring solution characteristics of a sample using a multi-layer active sensor.

Background Art

[0002] In medical settings such as hospitals and nursing homes, infections caused by anti-infective drug-resistant bacteria and microorganisms are a major problem. For example, in infectious diseases, chemicals released by infectious pathogens into the bloodstream can cause life-threatening complications, such as sepsis, which is well-known to cause dangerous systemic inflammatory reactions, as well as vasomotor reactions, fever, hypotension, and even death. When faced with such an infectious disease, it is a preferred measure for clinicians to use anti-infective drugs carefully, preferably only those necessary to alleviate the infectious disease.

[0003] However, currently, most frequently, a wide range of anti-infective drugs, often multiple drugs, are administered until the bacteria are identified and the drug susceptibility is tested, and the validity of the treatment is confirmed. As a result, there is a tendency for multiple drug-resistant infections to occur. Ideally, the sensitivity should be detected immediately after the presence of the infectious pathogen is confirmed. To determine the susceptibility of such an infectious pathogen to an anti-infective drug, it is necessary to quantify the sample containing the infectious pathogen, and for that, it is necessary to analyze the presence or absence of microbial growth in the sample.

[0004] Existing biosensors used for analyzing infectious agents and pathogens in biological samples and other types of samples often include an active sensing element and a reference sensing element that are in fluid contact or communication with the sample of interest. Current in vitro diagnostic measurement devices, particularly those for detecting the redox potential (ORP) and pH in biological and fluid samples, are often not designed with both high performance and low cost in mind. Furthermore, since it is important to prevent cross-contamination of patient samples, it is a preferred configuration that the sensing elements of the diagnostic measurement system are disposable consumables. Therefore, disposable sensing elements place considerable importance on cost and manufacturability.

[0005] Conventional biosensors often use expensive glass substrates or silicon substrates, which are correspondingly costly and require many manufacturing steps. Furthermore, the active sensing elements of such biosensors may malfunction if biological samples or other fluid samples inadvertently come into contact with the conductive part of the active sensing that is not intended to contact the sample. SUMMARY OF THE INVENTION PROBLEMS TO BE SOLVED BY THE INVENTION

[0006] Therefore, solutions are needed to solve the above problems and limitations. Such solutions are preferably disposable and cost-effective in manufacturing. However, such solutions also need to be capable of accurate measurement and be formed of highly biocompatible materials. MEANS FOR SOLVING THE PROBLEM

[0007] An apparatus, system, and method for measuring solution characteristics (e.g., ORP or pH) of a sample containing microorganisms are disclosed. In one embodiment, a sensor device for measuring solution characteristics of a sample is disclosed. The sensor device can be composed of a sample container consisting of a sample chamber. The sample chamber consists of chamber sidewalls surrounding a chamber cavity configured to receive the sample. The sensor device may also include a reference sensor consisting of a reference electrode material and a core in fluid communication with the sample chamber. At least a portion of the sample can be drawn by the core in the direction of the reference electrode material.

[0008] Alternatively, it can also be composed of an active sensor formed by covering a part of a conductive substrate with an active electrode layer. The active sensor can be coupled to at least a portion of the chamber sidewall at a window opening formed along the chamber sidewall. In some embodiments, no part of the active sensor extends into the chamber cavity. The active electrode layer can face the chamber cavity such that the sample in the chamber cavity can be in fluid contact with the active electrode layer through at least a portion of the chamber sidewall surrounding the window opening. By electrically connecting the reference sensor and the active sensor to a reader device, the solution characteristics of the sample can be determined based on the potential difference measured between the active sensor and the reference sensor.

[0009] The solution characteristic to be measured can be the oxidation-reduction potential. The solution characteristic to be measured may also be pH. The active electrode layer can consist of at least one of a platinum oxide layer (formed on a platinum layer) and a tantalum oxide layer. The conductive substrate can consist of stainless steel. The active electrode layer can have a thickness of the active electrode layer of about 50 nm to 500 nm. The active sensor can further include an adhesive layer between the conductive substrate and the active electrode layer. The adhesive layer can have a thickness of 5 nm to 50 nm. The ratio of the thickness of the adhesive layer to the thickness of the active electrode layer can be about 1:10 to 1:20. The adhesive layer can be any of a chromium layer, a gold layer, and a nickel layer.

[0010] The active layer can have an active electrode layer thickness of about 400 nm. While the sample container is being injection-molded, the active sensor can be insert-molded onto the chamber sidewall. The active sensor can be press-molded onto the chamber sidewall after the sample container has been injection-molded. The chamber sidewall can be composed of a recess surrounding a window opening. The recess can be formed along the outer side surface of the chamber sidewall. The active sensor can be adhered to at least a part of the chamber sidewall within the recess via an adhesive.

[0011] The active sensor can be composed of an active electrode side surface, a conductive substrate side surface opposite the active electrode side surface, and a side surface. The side surface is covered by at least one of the chamber sidewall and the adhesive, and the side surface can be prevented from contacting the sample. The sample chamber can be formed in part of at least one of polyoxymethylene, polyamide, polyethylene, acrylonitrile-butadiene-styrene, polycarbonate, and polypropylene. The reference electrode material can be a cured conductive ink vapor-deposited or otherwise applied to the proximal end of the core.

[0012] In some embodiments, the active sensor can be formed of a non-conductive printed circuit (PCB) substrate partially covered by an electrode layer. The active electrode layer can be electrically coupled to the conductive contacts of the PCB substrate by conductive vias extending through the PCB substrate. The PCB substrate can be a flexible PCB substrate.

[0013] The PCB substrate can be formed in part of polyimide, FR-4 composite material, copper, etc. The solution property to be measured can be the redox potential. The active electrode layer can be a platinum layer or a gold layer. The active electrode layer can have an active electrode layer of at least 50 nm. In certain embodiments, the active electrode layer can have an active electrode layer thickness of at least 400 nm.

[0014] In some embodiments, the active sensor can be formed on a non-conductive polymer substrate including a through-hole. One side of the polymer substrate and one end of the through-hole can be covered with a conductive layer. The active electrode layer can be electrically coupled to the conductive layer through a conductive coating covering the lateral side of the through-hole.

[0015] The active electrode layer can be a platinum layer or a gold layer. The active electrode layer can have an active electrode layer of at least 50 nm. In certain embodiments, the active electrode layer can have a thickness of the active electrode layer of at least 400 nm.

[0016] The active sensor can be a rectangular component having a width dimension between about 100 μm and 6.0 mm and a length dimension between about 100 μm and 6.0 mm. The diameter of the through-hole can be between about 10 μm and 100 μm. A conductive coating covering the lateral side of the through-hole can use a coating such as platinum or gold.

[0017] In some embodiments, the active sensor can be formed with a conductive post partially covered by the active electrode layer. The active sensor can be coupled to at least a part of the chamber sidewall at a window opening formed along the chamber sidewall. The portion of the conductive post covered by the active electrode layer of the active sensor can extend into the chamber cavity so that the sample in the chamber cavity can be in fluid contact with the active electrode layer. The end of the conductive post that does not extend into the chamber cavity can extend outside the chamber sidewall. The conductive post can be formed partially of stainless steel and can be shaped as a cylinder having a substantially rounded edge.

[0018] Also disclosed is a method for measuring the solution properties of a sample. This method may include cleaning a conductive substrate by acid and base treatment, depositing an adhesive layer on one side of the conductive substrate, and depositing an active electrode layer on the adhesive layer. This method may further include fragmenting the conductive substrate covered with the adhesive layer and the active electrode layer to obtain an active sensor sized to cover a window opening formed along the chamber sidewall of the sample chamber. This method may further include coupling the active sensor to at least a portion of the chamber sidewall such that no portion of the active sensor extends into the chamber cavity within the sample chamber and the active electrode layer faces the chamber cavity and any sample within the chamber cavity is in fluid contact with the active electrode layer through at least a portion of the chamber sidewall surrounding the window opening.

[0019] This method may further include treating the conductive substrate with ammonium hydroxide, isopropyl alcohol, or acetone after treating the conductive substrate with nitric acid. This method may further include laser cutting, metal shearing, thermal wire cutting, die cutting, stamping, or saw cutting the conductive substrate.

[0020] This method may further include applying a bead of adhesive to a portion of the chamber sidewall within a recess formed along the chamber sidewall surrounding the window opening. This method may further include pressing the active sensor onto the bead of adhesive within the recess and curing the adhesive.

[0021] This method may further include insert molding the active sensor onto the chamber sidewall during the formation of the sample chamber by injection molding. This method may further include locally melting a portion of the chamber sidewall surrounding the window opening, pressing the active sensor against the melted portion of the chamber sidewall, and cooling the melted portion of the chamber sidewall to affix the active sensor to the chamber sidewall.

[0022] The method can further include depositing an active electrode material that constitutes the active electrode layer until the thickness of the active electrode layer reaches at least 50 nm. In some embodiments, the method can include depositing an active electrode material that constitutes the active electrode layer until the thickness of the active electrode layer reaches at least 400 nm. In some embodiments, when the measured solution property is the redox potential (ORP) of the sample, the active electrode material can be platinum. The active electrode material can be deposited using sputter deposition, vapor deposition method, electrodeposition, ink screen printing, etc.

[0023] The method can further include depositing an adhesive material that constitutes the adhesive layer using sputter deposition. The adhesive layer can be deposited in a vacuum chamber, and the active electrode layer can be deposited in the same vacuum chamber following the adhesive layer.

[0024] When the property of the solution to be measured is the pH of the sample, the active electrode material can be a metal oxide. In some embodiments, the metal oxide can be platinum oxide, and the platinum oxide can cover a platinum layer deposited on the adhesive layer.

[0025] In some embodiments, a method of manufacturing a sensor device for measuring solution properties of a sample can include providing a non-conductive printed circuit (PCB) substrate and depositing an active electrode layer on one side of the PCB substrate. The active electrode layer can be electrically coupled to a conductive contact of the PCB substrate by a conductive via extending through the PCB substrate. The method can further include singulating the PCB substrate covered with the active electrode layer to obtain an active sensor sized to cover a window opening formed along a chamber sidewall of a sample chamber. The active sensor can include at least one conductive via extending through the PCB substrate. The method can further include coupling the active sensor to at least a portion of the chamber sidewall such that no portion of the active sensor extends into a chamber cavity within the sample chamber, the active electrode layer faces the chamber cavity, and any sample within the chamber cavity is in fluid contact with the active electrode layer through at least a portion of the chamber sidewall surrounding the window opening.

[0026] The method can further include depositing an active electrode material constituting the active electrode layer using sputter deposition, vapor deposition method, and electrodeposition. The active electrode material can be deposited until the thickness of the active electrode layer is at least 50 nm. In certain embodiments, the active electrode material can be deposited until the thickness of the active electrode layer is at least 400 nm. When the solution property to be measured is the oxidation-reduction potential (ORP) of the sample, the active electrode material can be platinum or gold. The conductive contact can be partially formed of gold.

[0027] In some embodiments, another method of manufacturing a sensor device can include providing a non-conductive polymer substrate that includes a plurality of through-holes, and depositing a conductive layer on one side of the polymer substrate. This method can further include depositing an active electrode layer on the other side of the polymer substrate. One end of each through-hole can be covered by the active electrode layer, and the other end of each through-hole can be covered by the conductive layer. The active electrode layer can be electrically coupled to the conductive layer via a conductive coating that covers the lateral sides of the through-holes after the deposition step. This method can further include singulating the polymer substrate covered with the active electrode layer and the conductive layer to obtain an active sensor sized to cover a window opening formed along a chamber sidewall of a sample chamber. The active sensor can include at least one through-hole covered by the active electrode layer and the conductive layer.

[0028] This method can further include coupling the active sensor to at least a portion of the chamber sidewall such that no part of the active sensor extends into the chamber cavity within the sample chamber, the active electrode layer faces the chamber cavity, and any sample within the chamber cavity is in fluid contact with the active electrode layer through at least a portion of the chamber sidewall that surrounds the window opening. Depositing the conductive layer can include depositing a conductive material on the other side of the polymer substrate. In some embodiments, the conductive material can be gold.

Brief Description of the Drawings

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Best Mode for Carrying Out the Invention

[0030] Aspects of the devices, systems, and methods described herein are best understood from the detailed description when read in conjunction with the accompanying drawings. In accordance with common practice, it is emphasized that the various elements of the drawings are not to scale. Dimensions of particular elements are enlarged or reduced for clarity, and not all elements are shown or labeled in all of the drawings. The drawings are provided for illustration only and are not intended to define or limit the claimed scope.

[0031] FIGS. 1A through 1D are diagrams showing embodiments of a sensor device 100 for measuring solution characteristics of a sample. In some embodiments, the solution characteristic to be measured can be the oxidation-reduction potential (ORP) of the sample. In other embodiments, the solution characteristic to be measured can be the pH of the sample.

[0032] In some embodiments, the sample can be obtained from a patient or subject. In other embodiments, the sample can be a biological sample, an environmental sample, or a food sample.

[0033] When the sample is obtained from a patient or subject, the sample can include at least one of the patient's or subject's body fluid and a swab obtained from the patient or subject.

[0034] In some embodiments, the patient or subject can be a human patient or subject. In other embodiments, the patient or subject can be a non-human animal patient or subject.

[0035] In some embodiments, the body fluid can be composed of blood, urine, serum, plasma, saliva, sputum, semen, breast milk, synovial fluid, cerebrospinal fluid such as spinal fluid, wound material, mucus, fluid associated with feces, vaginal secretion, synovial fluid, pleural fluid, peritoneal fluid, pericardial fluid, amniotic fluid, or a combination thereof.

[0036] In these and other embodiments, the swabs obtained from a patient or subject can consist of a wound swab, a rectal swab, a vaginal swab, a resuspended instance of the above-described swabs, or a combination thereof.

[0037] In all such embodiments, the sample can contain a plurality of microorganisms or infectious pathogens. The devices, systems, and methods disclosed herein can be used to evaluate the sample for the growth or absence of microorganisms as part of a microbial quantification procedure or an antibiotic susceptibility testing (AST) procedure.

[0038] In certain embodiments, the sample can contain or refer to a bacterial culture derived from at least one of a sample obtained from a patient or subject, a biological sample, an environmental sample, and a food sample. For example, the sample can contain or refer to a bacterial culture or a resuspended bacterial culture derived from a body fluid or a swab obtained from a patient or subject. As a more specific example, the sample can contain a bacterial culture or a resuspended bacterial culture derived from a body fluid or a swab obtained from a patient or subject determined to be positive for the growth of microorganisms.

[0039] More specifically, the sample can include a bacterial culture derived from blood obtained from a patient or subject determined to be positive for microbial growth. In some embodiments, the sample is or can indicate a positive blood culture. For the purposes of the present disclosure, a positive blood culture can be a bacterial culture derived from blood collected from a patient or subject determined to be positive for bacterial growth. For example, a patient exhibits symptoms of sepsis (such as high fever, chills, etc.), blood (e.g., 5 mL to 10 mL) is collected from the patient, and it is possible to transfer it to a commercially available blood culture container or vessel containing a bacterial growth medium (e.g., 30 mL to 40 mL of growth medium). Then, it can be cultured at 35°C plus or minus 2°C in the blood culture container or vessel to grow bacteria. If the patient's blood is contaminated with bacteria, the bacteria will multiply within the container or vessel. Subsequently, a blood culture system or device is used to monitor the growth of the bacteria (e.g., by monitoring the CO2 production of the bacteria in the container or vessel), and when the system or device meets the critical CO2 threshold, it can determine the sample as "positive" for bacterial growth. Depending on the type of pathogen and the growth rate, the blood culture becomes positive between 7 hours and 3 days. Such a "positive blood culture" can be used for further downstream tests, such as using any of the devices, systems, and methods disclosed herein.

[0040] In additional embodiments, the sample can include environmental samples obtained from rivers, streams, lakes, seas, contaminated sites, quarantine areas, emergency areas, or combinations thereof. In other embodiments, the sample can include food samples obtained from food processing facilities, canteens, waste facilities, or combinations thereof.

[0041] In some embodiments, an aqueous growth medium can be added to the sample before it is introduced into the sample container 104 of the sensor device 100. In other embodiments, the aqueous growth medium can be added to the sample when the sample is injected, delivered, infused, or otherwise introduced into the sample container 104.

[0042] In one embodiment, the aqueous growth medium can be Mueller-Hinton broth with glucose added (MHG). In other embodiments, the aqueous growth medium can be a solution containing bactotryptone, tryptic soy digest, yeast extract, beef extract, cation-adjusted Mueller-Hinton broth (CAMHB), starch, acid hydrolysate of casein, calcium chloride, magnesium chloride, sodium chloride, blood or hemolyzed horse serum (LHB), hemolyzed CAMHB-LHB, glucose or other carbohydrates, or combinations thereof.

[0043] Microorganisms or infectious pathogens that can be evaluated using the devices, methods, and systems disclosed herein can be any unicellular or multicellular organisms that perform metabolism, including bacteria and fungi. In certain embodiments, the microorganism or infectious pathogen can be, but is not limited to, Acinetobacter, Acetobacter, Actinomyces, Aerococcus, Aeromonas, Agrobacterium, Anaplasma, Azorhizobium, Azotobacter, Bacillus, Bacteroides, Bartonella, Bordetella, Borrelia, Brucella, Burkholderia, Campylobacter, Chlamydia, Chlamydophila, Citrobacter, Clostridium, Corynebacterium, Coxiella, Ehrlichia, Enterobacter, Enterococcus, Escherichia, Francisella, Fusobacterium, Gardnerella, Haemophilus, Helicobacter, Klebsiella, Lactobacillus, Legionella, Listeria, Methanobacterium, Microbacterium, Micrococcus, Morganella, Moraxella, Mycobacterium, Mycoplasma, Neisseria, Pandoraea, Pasteurella, Peptostreptococcus, Porphyromonas, Prevotella, Proteus, Providencia, Pseudomonas, Ralstonia, Raoultella, Rhizobium, Rickettsia, Rochalimaea, Rothia, Salmonella, Serratia, Shewanella, Shigella, Spirillum, Staphylococcus, Stenotrophomonas, Streptococcus, Streptomyces, Treponema, Vibrio, Wolbachia, Yersinia, or combinations thereof. In other embodiments, the microorganism or infectious pathogen can be one or more fungi selected from the genus Candida or Cryptococcus or mold.

[0044] Other specific bacteria that can be evaluated using the methods and systems disclosed herein can include Staphylococcus aureus, Staphylococcus lugdunensis, coagulase-negative staphylococcal species (including, but not limited to, Staphylococcus epidermidis, Staphylococcus haemolyticus, Staphylococcus hominis, Staphylococcus capitis, undifferentiated), Enterococcus faecalis, Enterococcus faecium (including, but not limited to, Enterococcus faecium and other Enterococcus species, undifferentiated, excluding Enterococcus faecalis), Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus agalactiae, streptococcal species (including, but not limited to, Streptococcus - mitis, Streptococcus pyogenes, Streptococcus gallolyticus, Streptococcus - agalactiae, Streptococcus pneumoniae, undifferentiated), Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella genus (including, but not limited to, Klebsiella - pneumoniae, Klebsiella - oxytoca, undifferentiated), Escherichia coli, Enterobacter genus (including, but not limited to, Enterobacter cloacae, Enterobacter aerogenes, undifferentiated), Proteus genus (including, but not limited to, Proteus - mirabilis, Proteus - vulgaris, undifferentiated), Citrobacter genus (including, but not limited to, Citrobacter - freundii, Citrobacter koseri, undifferentiated), Serratia marcescens, Candida albicans, Candida glabrata, Candida tropicalis.

[0045] Other more specific bacteria that can be evaluated include, among others, Acinetobacter baumannii, Actinobacillus spp., Actinomyces, Actinomyces spp. (including but not limited to Actinomyces israelii and Actinomyces neerlandicus), Aeromonas spp. (including but not limited to Aeromonas hydrophila, Aeromonas veronii biovar sobria (Aeromonas sobria), and Aeromonas caviae), Anaplasma phagocytophilum, Alcaligenes faecalis, Actinobacillus actinomycetemcomitans, Bacillus spp. (including but not limited to Bacillus anthracis, Bacillus cereus, Bacillus subtilis, Bacillus thuringiensis, and Bacillus stearothermophilus), Bacteroides spp. (including but not limited to Bacteroides fragilis), Bartonella spp. (including but not limited to Bartonella bacilliformis and Bartonella henselae), Bifidobacterium spp., Bordetella spp. (including but not limited to Bordetella pertussis, Bordetella parapertussis, and Bordetella bronchiseptica), Borrelia spp. (including but not limited to Borrelia recurrentis and Borrelia burgdorferi), Brucella spp. (including but not limited to Brucella abortus, Brucella canis, Brucella melitensis, and Brucella suis), Burkholderia spp. (including but not limited to Burkholderia pseudomallei and Burkholderia cepacia), Campylobacter spp. (including but not limited to Campylobacter jejuni, Campylobacter coli, Campylobacter lari, and Campylobacter fetus), Capnocytophaga spp., Cardiobacterium hominis, Chlamydia trachomatis, Chlamydophila pneumoniae, Chlamydophila psittaci, Citrobacter spp., Coxiella burnetii, Corynebacterium spp. (including but not limited to Corynebacterium diphtheriae, Corynebacterium jeikeium, and Corynebacterium spp.),Clostridium spp. (including but not limited to Clostridium perfringens, Clostridium difficile, Clostridium botulinum, and Clostridium tetani), Eikenella corrodens, Enterobacter spp. (including but not limited to Enterobacter aerogenes, Enterobacter - agglomerans, Enterobacter - cloacae, and Escherichia coli (including but not limited to opportunistic E. coli. Opportunistic E. coli includes, but is not limited to, enterotoxigenic E. coli, enteroinvasive E. coli, enterohemorrhagic E. coli, enteroadherent E. coli, and uropathogenic E. coli)), Enterococcus spp. (including but not limited to Enterococcus faecalis and Enterococcus faecium), Ehrlichia spp. (including but not limited to Ehrlichia chaffeensis and Ehrlichia canis), Erysipelothrix rhusiopathiae, Eubacterium spp., Francisella tularensis, Fusobacterium nucleatum, Gardnerella vaginalis, Gemella morbillorum, Haemophilus spp. (including but not limited to Haemophilus influenza, Haemophilus ducreyi, Haemophilus aegyptius, Haemophilus parainfluenza, Haemophilus haemolyticus, and Haemophilus parahemolyticus), Helicobacter spp. (including but not limited to Helicobacter pylori, Helicobacter cinaedi, and Helicobacter fennelliae), Kingella kingae, Klebsiella spp. (including but not limited to Klebsiella pneumoniae, Klebsiella granulomatis, and Klebsiella oxytoca), Lactobacillus spp., Listeria monocytogenes, Leptospira interrogans, Legionella pneumophila, Leptospira interrogans, Peptostreptococcus spp., Moraxella catarrhalis, Morganella spp., Mobiluncus spp., Micrococcus spp., Mycobacterium spp. (including but not limited to Mycobacterium leprae, Mycobacterium tuberculosis, Mycobacterium intracellulare, Mycobacterium avium, Mycobacterium bovis, and Mycobacterium marinum),(but not limited to), Mycoplasma spp. (including, but not limited to, Mycoplasma pneumoniae, Mycoplasma hominis, and Mycoplasma genitalium), Nocardia spp. (including, but not limited to, Nocardia asteroides, Nocardia cyriacigeorgica, and Nocardia brasiliensis), Neisseria spp. (including, but not limited to, Neisseria gonorrhoeae, and Neisseria meningitidis), Pasteurella multocida, Prevotella shigelloides, Prevotella spp., Porphyromonas spp., Prevotella melaninogenica, Proteus spp. (including, but not limited to, Proteus vulgaris and Proteus mirabilis), Providencia spp. (including, but not limited to, Providencia alcalifaciens, Providencia rettgeri, and Providencia stuartii), Pseudomonas aeruginosa, Propionibacterium acnes, Rhodococcus equi, Rickettsia spp. (including, but not limited to, Rickettsia rickettsii, Rickettsia akari, and Rickettsia prowazekii, Orientia tsutsugamushi (formerly Rickettsia tsutsugamushi), and Rickettsia typhi), Rhodococcus spp., Stenotrophomonas maltophilia, Salmonella spp. (including, but not limited to, Salmonella enterica, Salmonella typhi, Salmonella paratyphi, Salmonella enteritidis, Salmonella cholerasuis, and Salmonella typhimurium), Serratia spp. (including, but not limited to, Serratia marcescens and Serratia liquefaciens), Shigella spp. (including, but not limited to, Shigella dysenteriae, Shigella flexneri, Shigella boydii, and Shigella sonnei), Staphylococcus spp. (including, but not limited to, Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus haemolyticus, and Staphylococcus saprophyticus), Streptococcus spp. (pneumococci (e.g., chloramphenicol-resistant serotype 4 pneumococci, spectinomycin-resistant serotype 6B Streptococcus pneumoniae, streptomycin-resistant serotype 9V Streptococcus pneumoniae, erythromycin-resistant serotype 14 Streptococcus pneumoniae,Optochin-resistant Streptococcus pneumoniae serotype 14, rifampicin-resistant Streptococcus pneumoniae serotype 18C, tetracycline-resistant Streptococcus pneumoniae serotype 19F, penicillin-resistant Streptococcus pneumoniae serotype 19F, and trimethoprim-resistant Streptococcus pneumoniae serotype 2,3F, chloramphenicol-resistant Streptococcus pneumoniae serotype 4, spectinomycin-resistant Streptococcus pneumoniae serotype 6B, streptomycin-resistant Streptococcus pneumoniae serotype 9V, optochin-resistant Streptococcus pneumoniae serotype 14, rifampicin-resistant Streptococcus pneumoniae serotype 18C, penicillin-resistant Streptococcus pneumoniae serotype 19F, or trimethoprim-resistant Streptococcus pneumoniae serotype 23F), Streptococcus agalactiae, Streptococcus mutans, Streptococcus pyogenes, group A Streptococcus, Streptococcus pyogenes, group B Streptococcus, Streptococcus agalactiae, group C Streptococcus, Streptococcus anginosus, Streptococcus eximius, group D Streptococcus, Streptococcus bovis, group F Streptococcus, Streptococcus anginosus, and group G Streptococcus, including but not limited to these), Spirillum minor, Streptobacillus moniliformis, Treponema spp. (including but not limited to Treponema carateum, Treponema pertenue, Treponema pallidum, and Treponema endemicum), Tropheryma whipplei, Ureaplasma urealyticum, Veillonella spp., Vibrio spp. (including but not limited to Vibrio cholerae, Vibrio parahaemolyticus, Vibrio vulnificus, Vibrio parahaemolyticus, Vibrio vulnificus, Vibrio alginolyticus, Vibrio mimicus, Vibrio hollisae, Vibrio fluvialis, Vibrio metschnikovii, Vibrio damsela, and Vibrio furnissii), Yersinia spp. (including but not limited to Yersinia enterocolitica, Yersinia pestis, and Yersinia pseudotuberculosis), and may include Xanthomonas maltophilia.,

[0046] Furthermore, other microorganisms or infectious pathogens that can be evaluated using the methods and systems disclosed herein include, but are not limited to, Candida species (including Candida albicans, Candida glabrata, Candida tropicalis, Candida parapsilosis, and Candida krusei), Aspergillus species (including Aspergillus fumigatus, Aspergillus flavus, and Aspergillus clavatus, but not limited thereto), Cryptococcus species (including Cryptococcus neoformans, Cryptococcus gattii, Cryptococcus laurentii, and Cryptococcus albidus, but not limited thereto), Fusarium species (including Fusarium oxysporum, Fusarium solani, Fusarium verticillioides, and Fusarium proliferatum, but not limited thereto), Rhizopus - oryzae, Penicillium marneffei, Coccidioides immitis, and Blastomyces dermatitidis, and can include fungi or molds not limited to these.

[0047] FIG. 1A is a front view showing a sensor device 100 according to one embodiment for measuring the solution characteristics of a sample. The sensor device 100 can include a sample container 104 including a sample chamber 108, a reference sensor 122 formed as part of a container cap 116 (see, e.g., FIG. 1D), and an active sensor 106 coupled to at least a portion of the sample chamber 108. The container cap 116 can be removably or detachably coupled or fixed to the sample container 104 (e.g., screwed or pressed onto the top of the sample container 104).

[0048] The sample container 104 can be formed partly of an inert material or a non-conductive material. In some embodiments, the sample container 104 can be formed of, or partly formed of, a polymeric material, a ceramic material, or glass, or a combination thereof. As a more specific example, the sample container 104 can be formed of, or partly formed of, polyvinyl chloride (PVC), poly(methyl methacrylate) (PMMA), polydimethylsiloxane (PDMS), or a combination thereof.

[0049] FIG. 1B is a side cross-sectional view showing a part of the sensor device 100. FIG. 1B shows that the sample chamber 108 can consist of a chamber sidewall 112 surrounding a chamber cavity 109 configured to receive a sample. The active sensor 106 can be attached, adhered, or otherwise coupled to the chamber sidewall 112 of the sample container 104. In other embodiments not shown, the active sensor 106 can be coupled to, or positioned along, the bottom of the sample container 104.

[0050] The active sensor 106 can be coupled to at least a part of the chamber sidewall 112 at a window opening 114 formed along the chamber sidewall 112. The chamber sidewall 112 can include a recess 134 surrounding the window opening 114. The recess 134 can be formed along the outer side surface of the chamber sidewall 112.

[0051] Regarding the arrangement of the active sensor 106, as shown in FIG. 1C, the active sensor 106 can be configured such that no part of the active sensor 106 extends into the chamber cavity 109.

[0052] As will be described in more detail below, the active sensor 106 can be formed of a conductive substrate partially covered by an active electrode layer 132. The active electrode layer 132 of the active sensor 106 can face the chamber cavity 109 such that a sample within the chamber cavity 109 is in fluid contact with the active electrode layer 132 through at least a portion of the chamber sidewall 112 surrounding the window opening 114.

[0053] FIG. 1C is a cutaway perspective view showing the active sensor 106 adhered to the chamber sidewall 112. In the embodiment shown in FIG. 1C, the active sensor 106 is adhered to the recess 134 of the chamber sidewall 112. At least a portion of the active electrode layer 132 of the active sensor 106 can cover the window opening 114 formed along the chamber sidewall 112 such that this portion of the active electrode layer 132 covering the window opening 114 is positioned to be in fluid communication with the chamber cavity 109 of the sample chamber 108. When the sample chamber 108 is filled with a sample, the sample can be in fluid contact with the portion of the active electrode layer 132 covering the window opening 114.

[0054] FIG. 1C also shows that the sides of the active sensor 106 can be covered by an adhesive 138. Since the active sensor 106 can be composed of multiple layers, the adhesive 138 can protect specific layers of the active sensor 106 from unwanted contact with the fluid sample. The adhesive 138 can function as a barrier to prevent the fluid sample from contacting the lateral sides 136 of the active sensor 106. In other embodiments contemplated by the present disclosure but not shown in the figure, the recess 134 of the chamber sidewall 112 can be sized such that the active sensor 106 fits tightly within the recess 134 and the walls of the recess 134 are adjacent or joined to the lateral sides 136 of the active sensor 106. Thereby, only the exposed portion of the active electrode layer 132 can be reliably brought into contact with the fluid sample, whereby the solution characteristics of the fluid sample can be measured more accurately.

[0055] To adhere the active sensor 106 to the sample chamber 108, beads of the adhesive 138 can be applied to the inner shelf portion 140 and / or the side edges 142 of the recess 134, and then the active sensor 106 can be pushed into the recess 134 with the end effector of a pick-and-place machine. The active sensor 106 can be pushed into the recess 134 or otherwise biased until the surface facing the outside of the active sensor 106 is flush with the outer surface of the chamber sidewall 112.

[0056] The adhesive 138 can then be cured to fix the active sensor 106 in place. In some embodiments, the adhesive 138 can be a medical-grade ultraviolet-curable adhesive. For example, the adhesive 138 can be the Dimax® 1405M-T-UR-SC adhesive (curable using LED light with a wavelength of about 405 nm). In other embodiments, the adhesive 138 can be any low-outgassing medical-grade adhesive.

[0057] As described above, the active sensor 106 can be formed of a conductive substrate partially covered by the active electrode layer 132. The active sensor 106 is positioned such that the active electrode layer 132 faces the chamber cavity 109, and the sample within the chamber cavity 109 can be in fluid contact with the active electrode layer 132 through at least a portion of the chamber sidewall 112 surrounding the window opening 114. In this embodiment, the active sensor 106 (including the active electrode layer 132) is positioned radially outward from the side facing the inside of the chamber sidewall 112 or the side facing the cavity, and the lateral side surface 136 of the active sensor 106 is not exposed to the fluid sample.

[0058] In some embodiments, the solution property to be measured or monitored can be the pH of the sample. When the solution property to be measured or monitored is pH, the active electrode layer 132 can be a material highly sensitive to pH. For example, the material highly sensitive to pH can be any one of, or a combination of, or include silicon dioxide (SiO2), aluminum oxide (Al2O3), titanium dioxide (TiO2), tantalum oxide / pentoxide (Ta2O5), hafnium dioxide (HfO2), iridium dioxide (IrO2), ruthenium dioxide (RuO2), zirconium dioxide (ZrO2).

[0059] In these and other embodiments, the solution property to be measured or monitored can be the oxidation-reduction potential (ORP) of the sample. When the solution property to be measured or monitored is the ORP of the sample, the active electrode layer 132 can be a material highly sensitive to oxidation-reduction. For example, the material highly sensitive to oxidation-reduction can be any one of, or a combination of, or consist of platinum (Pt), gold (Au), a metal oxide highly sensitive to oxidation-reduction, or a combination thereof. More specifically, the material highly sensitive to oxidation-reduction can be any one of, or a combination of, or include silicon dioxide (SiO2), aluminum oxide (Al2O3), titanium dioxide (TiO2), tantalum pentoxide (Ta2O5), hafnium dioxide (HfO2), iridium dioxide (IrO2), ruthenium dioxide (RuO2), zirconium dioxide (ZrO2). Details regarding the formation of the active sensor 106 will be described later.

[0060] Although not shown, it is contemplated by the present disclosure that the sensor device 100 can be designed such that both the pH and ORP of the sample are measured simultaneously. For example, the sample chamber 108 of the sensor device 100 can include a plurality of window openings 114 formed along the chamber sidewall 112 of the sample chamber 108. Each of these window openings 114 can subsequently be covered by a different active sensor 106 (e.g., one window opening 114 can be covered by an active sensor 106 having an active electrode layer 132 formed from a material highly sensitive to redox, and another window opening 114 can be covered by an active sensor 106 having an active electrode layer 132 formed from a material highly sensitive to pH).

[0061] The sensor device 100 can have a height of the device. In some embodiments, the height of the device can be from about 20.0 mm to about 50.0 mm. In some embodiments, the height of the device can be from about 25.0 mm to about 35.0 mm. For example, the height of the device can be about 31.3 mm.

[0062] FIG. 1D illustrates that the reference sensor 122 can be formed as part of the container cap 116. The reference sensor 122 can include a reference conduit 118 that includes a reference conduit cavity 120 (see, e.g., FIG. 1B). The reference conduit cavity 120 can have first and second openings at opposite ends of the reference conduit cavity 120. The reference conduit 118 can be an elongate channel or passage configured to extend into the chamber cavity 109 of the sample chamber 108.

[0063] The reference sensor 122 can further include a reference electrode material 149 and a core element 150 that are in fluid communication with the chamber cavity 109. The reference conduit cavity 120 can accommodate the core element 150. At least a portion of the sample can be drawn by the core element 150 in the direction of the reference electrode material 149.

[0064] The reference conduit 118 can be tapered such that the volume of the reference conduit cavity 120 tapers or narrows towards the tip from the reference conduit proximal end 126 to the reference conduit distal end 128 (see, e.g., FIG. 1B). The shape of the core element 150 can conform to or correspond to the shape of the reference conduit cavity 120. The shape of the core element 150 can be configured to taper or narrow towards the tip from the core proximal end 152 to the core distal end 154.

[0065] The core element 150 can extend through the length of the reference conduit cavity 120. In some embodiments, the core element 150 can fill or occupy all of the space within the reference conduit cavity 120. In other embodiments, the core element 150 can partially fill or occupy the space within the reference conduit cavity 120.

[0066] At least a portion of the core element 150 can be in fluid communication with the chamber cavity 109 of the sample chamber 108 such that when the sample chamber 108 is filled with a sample, at least a portion of the sample within the sample chamber 108 is drawn, absorbed, or otherwise aspirated in the direction of the core proximal end 152 by at least a portion of the core distal end 154. The core element 150 can be formed of a polymeric material that draws the fluid sample towards the reference electrode material 149 by capillary action.

[0067] In some embodiments, at least a portion of the core distal end 154 can extend beyond the second opening of the reference conduit such that the core distal end 154 projects or extends into the chamber cavity 109 of the sample chamber 108. In these embodiments, the core distal end 154 can extend or project into the sample when the sample chamber 108 is filled with the sample.

[0068] In other embodiments, the core distal end 154 is positioned proximal or above the second opening of the reference conduit such that the core distal end 154 does not project or extend into the chamber cavity 109 of the sample chamber 108. In these embodiments, the core distal end 154 can still be in fluid communication with the sample chamber 108, and the fluid sample can still reach or contact the core distal end 154 by being drawn into the reference conduit 118 by capillary action or by rocking the sample container 104.

[0069] As described above, the core element 150 can be formed in part of a porous material. The core element 150 can be formed in part of a material having pores sized from 15 μm to about 150 μm (e.g., about 50 μm). In some embodiments, the core element 150 can be formed in part of a polymeric material. As a more specific example, the core element 150 can be formed in part of a porous polymeric material having pores sized from 15 μm to about 150 μm. In one embodiment, the core element 150 can be formed in part of high density polyethylene (HDPE). For example, the core element 150 can be formed in part of HDPE having pores sized about 50 μm. In other embodiments, the core element 150 can be formed in part of natural fibers. For example, the core element 150 can be formed in part of cellulose fibers, pulp, paper, cotton, or combinations thereof.

[0070] Further, the core element 150 can be treated with a surfactant such that at least one surface of the core element 150 is covered by the surfactant. In some embodiments, the core element 150 can be saturated with the surfactant or immersed in a solution containing the surfactant before being introduced into the reference conduit cavity 120. The surfactant can be configured to enhance the hydrophilicity of the core element 150 (i.e., to make the substantially hydrophobic surface of the core element 150 more hydrophilic). In some embodiments, the surfactant can be a fluorinated surfactant. In other embodiments, the surfactant can be a nonionic surfactant such as one or more poloxamers. As a more specific example, the surfactant can consist of Pluronic® F-68.

[0071] In one embodiment, the reference conduit 118 is formed in a generally conical or frustoconical shape and has a reference conduit cavity 120 that is similarly formed in a generally conical or frustoconical shape. In other embodiments, the reference conduit 118 can be substantially formed in the shape of an elongate pyramid having a polygonal bottom. For example, the reference conduit 118 can be substantially formed as an elongate triangular pyramid, square pyramid, or pentagonal pyramid. In additional embodiments, the reference conduit 118 can be substantially formed as a cylinder having a reference conduit cavity 120 in a generally cylindrical shape. In these embodiments, the reference conduit 118 can have a reference conduit distal end 128 that tapers towards the tip (see, e.g., FIG. 1B).

[0072] As shown in FIG. 1D, at least a portion of the core element 150 can be in fluid contact with the sample within the sample chamber 108. At least a portion of the sample can be drawn in the direction of the core proximal end 152 by the core element 150. The reference electrode material 149 can be disposed at the core proximal end 152. FIG. 1D also illustrates that at least a portion of the active electrode layer 132 can be in fluid contact with the sample within the sample chamber 108. When the core element 150 draws or sucks up the sample, the sample reaches the reference electrode material 149, and the charge carriers in the sample can establish an electrical connection between the reference electrode material 149 of the reference sensor 122 and the active electrode layer 132 of the active sensor 106. When both the reference sensor 122 and the active sensor 106 are electrically coupled to the reader device 190, the reader device 190 can be used to measure the solution properties of the sample.

[0073] The solution properties of the sample can be determined based on the potential difference measured between the active sensor 106 and the reference sensor 122 when the reference sensor 122 and the active sensor 106 are electrically coupled to the reader device 190. For example, the reference sensor 122 can provide a stable half-cell potential compared to the active sensor 106 when both the reference electrode material 149 and the active electrode layer 132 are in fluid contact with the sample within the sample chamber 108.

[0074] In some embodiments, the reference electrode material 149 can be a conductive ink coated or dispensed onto the core proximal end 152. The conductive ink coated or dispensed onto the core proximal end 152 can be solidified by curing. More specifically, the conductive ink can be silver-silver chloride (Ag-AgCl) ink.

[0075] At least a portion of the reference electrode material 149 can be coupled to the core element 150. For example, the reference electrode material 149 can be a cured mass disposed at the core proximal end 152. In certain embodiments, the reference electrode material 149 can be disposed at the center of the container cap 116. In some embodiments, at least a portion of the reference electrode material 149 can project or extend beyond the container cap 116.

[0076] One advantage of the core element 150 disclosed herein is that the core element 150 can draw up a sample and the sample can advance by capillary action through the pores of the core element 150 toward the reference electrode material 149. For example, a liquid sample can be drawn up to the core proximal end 152 that is in fluid contact with the reference electrode material 149. When the reference electrode material 149 is formed of a material such as silver-silver chloride (Ag-AgCl), the core element 150 can function as a barrier or obstacle to silver ions (Ag + ) that would otherwise freely diffuse into the sample in the sample chamber 108. Such silver ions can be harmful to the growth of microorganisms and infectious pathogens in the sample or have other effects. The core element 150 can act as a barrier or obstacle to silver ions by slowing or stopping the diffusion of the harmful silver ions into the sample. The core element 150 having the dimensions and shape disclosed herein is effective in slowing or stopping the diffusion of such harmful ions.

[0077] When the reference sensor 122 is implemented as the container cap 116, the container cap 116 may have dimensions formed by the cap width (or diameter) and the cap height. In some embodiments, the width of the cap can be from about 10.0 mm to about 20.0 mm. For example, the width of the cap can be about 15.7 mm. In some embodiments, the height of the cap can be from about 5.0 mm to about 20.0 mm. For example, the height of the cap can be about 10.5 mm. When the container cap 116 is fixed, attached, or otherwise coupled to the sample container 104, the sensor device 100 can have a height of the device measured from the bottom of the sample container 104 to the cap top 130 of the container cap 116.

[0078] The core element 150 can have a core height that is measured from the core proximal end 142 to the core distal end. In some embodiments, the core height can be from about 10.0 mm to about 20.0 mm. More specifically, the core height can be from about 14.0 mm to about 15.0 mm. For example, the core height can be about 14.8 mm.

[0079] As shown in FIG. 1D, the reference electrode material 149 can be positioned or disposed at least partially within the central dimple, depression, or recessed region of the container cap 116 over the core element 150. When the reference sensor 122 is a cured conductive ink or solution (e.g., Ag-AgCl ink), the dimple, depression, or recessed region can function as a receiving space for the liquid ink or solution to be cured.

[0080] In some embodiments, the reference electrode material 149 can have a reference electrode height and a reference electrode width. The height of the reference electrode can be from about 0.2 mm to 1.0 mm. For example, the height of the reference electrode can be about 0.4 mm. The width of the reference electrode can be from about 2.0 mm to about 5.0 mm. For example, the width of the reference electrode can be about 3.0 mm. One advantage of the reference sensor 122 disclosed herein is that the reference sensor 122 can function as a stable reference electrode or provide a stable reference potential during a test or operation of up to 10 hours.

[0081] FIG. 1D also shows that the sensor device 100 can include an aeration port 160 formed along the bottom side of the sample chamber 108. In other embodiments (not shown), the aeration port 160 can be formed along the chamber sidewall 112 of the sample chamber 108.

[0082] The aeration port 160 can be covered by a first air-permeable membrane. The aeration port 160 and the first air-permeable membrane can be configured such that the gas 162 can enter the sample chamber 108.

[0083] In some embodiments, the gas 162 can be ambient air (e.g., air within a laboratory, clinical environment, or test facility). In other embodiments, the gas 162 can consist of a combination of pressurized oxygen, carbon dioxide, nitrogen, and argon. By aerating the sample, an oxygen-rich environment can be provided within the sample chamber 108, thereby accelerating the growth of the microbial population within the sample.

[0084] In an alternative embodiment (not shown), the aeration port 160 can be formed along the cap top 130 of the container cap 116, and the gas 162 can be pumped into the sample chamber 108 from the top of the sample container 104.

[0085] Gas 162 (e.g., ambient air) can be pumped into the sample chamber 108 by a micropump or other pump-type device integrally incorporated within the leader device 190. Gas 162 (e.g., ambient air) can be pumped or oriented into the sample chamber 108 at a constant flow rate of about 1.0 to 10.0 mL / min through the aeration port 160 and the first air-permeable membrane. In other embodiments, Gas 162 (e.g., ambient air) can be pumped or oriented into the sample chamber 108 through the aeration port 160 and the first air-permeable membrane at a specific duty cycle or interval.

[0086] In certain embodiments, the second air-permeable membrane can cover at least a portion of the lower surface of the container cap 116. The second air-permeable membrane allows any gas 162 that is pumped or otherwise oriented into the sample chamber 108 to exit the sample chamber 108 while preventing any liquid within the sample chamber 108 from spilling out of the sample container 104.

[0087] In some embodiments, the first air-permeable membrane and the second air-permeable membrane can be formed of the same material. The first air-permeable membrane and the second air-permeable membrane can be formed from a hydrophobic air-permeable film or a thin sheet. For example, both the first air-permeable membrane and the second air-permeable membrane can be formed from or include polytetrafluoroethylene (PTFE).

[0088] As shown in FIG. 1D, the container cap 116 can be removably or detachably coupled or fixed to the sample container 104 by being screwed to the proximal portion of the sample container 104 via the screw connection portion 164. When the container cap 116 (functioning as part of the reference sensor 122) is fixed or coupled to the sample container 104 by the screw connection portion 164, air can enter the aeration port 160 in the sample chamber 108 through the first air permeable membrane, so that an air flow path 166 can be formed. The air then exits the sample chamber 108 through the second air permeable membrane and the air gap 168 formed between the threads of the container cap 116 and the threads of the sample container 104.

[0089] The container cap 116 can be formed of a material that is partially permeable or transparent, or a permeable or transparent non-conductive material. In other embodiments, the container cap 116 can be formed partially of a translucent or transparent material. For example, at least a portion of the core element 150 is visible through the side of the container cap 116. Thereby, the user or operator of the sensor device 100 can observe the suction of the fluid sample from the core distal end 154 to the core proximal end 152 when the container cap 116 is fixed to the sample container 104, and ensure that at least a portion of the sample can reach the reference electrode material 149 at the core proximal end 152. In some embodiments, the container cap 116 can be formed of a polymer material, glass, or a combination thereof that is partially transparent or permeable.

[0090] In some embodiments, the sample container 104, the container cap 116, or a combination thereof can be partially formed of an inert polymeric material. For example, the sample container 104, the container cap 116, or a combination thereof can be partially formed of at least one of polyoxymethylene, polyamide, polyethylene, acrylonitrile-butadiene-styrene, polycarbonate, polypropylene, or a copolymer or composite thereof. In other embodiments, the sample container 104, the container cap 116, or a combination thereof can be partially formed of a glass material such as borosilicate glass or a ceramic material.

[0091] FIG. 2 illustrates that when the sample container 104 is formed of a polymeric material, the active sensor 106 can also be insert molded into a portion of the chamber sidewall 112. For example, the active sensor 106 can be insert molded into the chamber sidewall 112 while the sample container 104 is being formed by injection molding.

[0092] When the active sensor 106 is insert molded into a portion of the chamber sidewall 112 of the sample chamber 108, the lateral side surface 136 of the active sensor 106 can be sealed by the polymeric material used to form the chamber sidewall 112.

[0093] In the embodiment shown in FIG. 2, the active sensor 106 can be insert molded such that the active electrode layer 132 faces the chamber cavity 109, and the sample within the chamber cavity 109 can be in fluid contact with the active electrode layer 132 through at least a portion of the chamber sidewall 112 that surrounds the window opening 114.

[0094] Figures 3A and 3B are black and white images showing the active sensor 106 insert molded into a polymeric material representing the material used to construct the chamber sidewall 112 of the sample chamber 108 (see, e.g., FIGS. 1A - 1D). In some embodiments, the sample chamber 108 can be formed in part of an inert polymeric material such as polyoxymethylene, polyamide, polyethylene, acrylonitrile - butadiene - styrene, polycarbonate, or polypropylene.

[0095] Figure 3A is a top plan view showing a side of the active sensor 106 covered by the active electrode layer 132. As described above, the active sensor 106 can be insert molded such that the active electrode layer 132 faces the chamber cavity 109 so that a sample within the chamber cavity 109 (see, e.g., FIG. 1D) can be in fluid contact with the exposed region of the active electrode layer 132.

[0096] Figure 3B is a top view showing the side of the active sensor 106 opposite the active electrode layer 132. The side of the active sensor 106 shown in FIG. 3B can be used to contact the conductive connection of the reader device 190 (see, e.g., FIGS. 14 and 15). As will be described in more detail below, this side of the active sensor 106 can be referred to as a conductive layer.

[0097] As shown in FIGS. 3A and 3B, the lateral sides 136 of the active sensor 106 can be sealed by the polymeric material. This allows only the exposed portion of the active electrode layer 132 to be reliably in contact with the fluid sample within the sample chamber 108, thereby enabling the solution properties of the fluid sample to be measured more accurately.

[0098] Although not shown, it is contemplated by the present disclosure that a portion of the chamber sidewall 112 surrounding the window opening 114 (see FIGS. 1B - 1D for the position of the window opening 114, for example) can be locally melted (e.g., by ultrasonic welding), and the active sensor 106 can be attached or otherwise coupled to the chamber sidewall 112 by pressing the active sensor 106 against the melted portion on the chamber sidewall 112. Once the melted portion of the chamber sidewall 112 is cooled, the active sensor 106 is then attached or coupled to the chamber sidewall 112.

[0099] FIG. 4A is a perspective view showing an active sensor 106 according to one embodiment in a state where two of its lateral sides 136 are visible. As shown in FIG. 4A, the active sensor 106 can be in the shape of a substantially flattened or head - truncated rectangular prism. In other embodiments, the active sensor 106 can be substantially disk - shaped or can be formed in the shape of a flattened or head - truncated polygonal prism (e.g., a flattened or head - truncated pentagonal prism or hexagonal prism).

[0100] FIG. 4A also shows that when the active sensor 106 is formed in the shape of a substantially rectangular prism, the active sensor 106 can have a sensor length dimension 400, a sensor width dimension 402, and a sensor height dimension 404. In some embodiments, the sensor length dimension 400 can be from about 100 μm to 6.0 mm, the sensor width dimension 402 can be from about 100 μm to 6.0 mm, and the sensor height dimension 404 can be from about 10 μm to 0.70 mm. For example, when the active sensor 106 is formed in the shape of a substantially rectangular prism, the active sensor 106 can have a sensor length dimension 400 of about 6.0 mm, a sensor width dimension 402 of about 6.0 mm, and a sensor height dimension 404 of about 0.61 mm.

[0101] Figure 4B is a side view of an active sensor 106 according to one embodiment, which is used to measure the oxidation-reduction potential (ORP) of a sample. In this embodiment, the active sensor 106 can have an active electrode layer 132 formed of a noble metal. For example, the active electrode layer 132 can be made of platinum, gold, or a combination or composite thereof.

[0102] The active electrode layer 132 can be adhered to one side of the conductive substrate 406 via an adhesive layer 408. The conductive substrate 406 can be formed of a conductive material such as stainless steel (SS). For example, the conductive substrate 406 can be SS316. In other embodiments, the conductive substrate 406 can be formed of aluminum, copper, or any combination or composite of aluminum, copper, or stainless steel.

[0103] In some embodiments, the adhesive layer 408 can be a thin layer of chromium (Cr). Alternatively, the adhesive layer 408 can be a thin layer of gold, nickel, titanium, or tantalum. The adhesive layer 408 can be disposed between the conductive substrate 406 and the active electrode layer 132.

[0104] In an alternative embodiment, the active electrode layer 132 can be directly deposited on one side of the conductive substrate 406 without the adhesive layer 408.

[0105] The active electrode layer 132 can have a thickness 410 of the active electrode layer of about 50 nm to 500 nm (for example, about 400 nm). The adhesive layer 408 can have a thickness 412 of the adhesive layer of about 5 nm to 50 nm (for example, about 20 nm). The ratio of the thickness 412 of the adhesive layer to the thickness 410 of the active electrode layer can be about 1:10 to 1:20.

[0106] The conductive substrate 406 can have a thickness 414 of the substrate layer. The thickness of the substrate layer can be about 10 μm to 0.70 mm (for example, about 0.61 mm).

[0107] FIG. 4C is a side view showing an alternative active sensor 106 used to measure the pH of a sample. In this embodiment, the active sensor 106 can have an active electrode layer 132 made of a material highly sensitive to pH. The material highly sensitive to pH can be deposited as a layer directly on the conductive substrate 406 or via an adhesive layer 408.

[0108] For example, the active electrode layer 132 can be formed of a metal oxide. For example, the active electrode layer 132 can be formed of tantalum pentoxide (Ta2O5). In other embodiments, the active electrode layer 132 can be formed of silicon dioxide (SiO2), silicon nitride (Si3N4), aluminum oxide (Al2O3), titanium dioxide (TiO2), hafnium dioxide (HfO2), iridium dioxide (IrO2), ruthenium dioxide (RuO2), zirconium dioxide (ZrO2), or a combination or composite thereof.

[0109] The conductive substrate 406 can be formed of a conductive material such as stainless steel (SS). For example, the conductive material can be SS316. In other embodiments, the conductive substrate 406 can be formed of aluminum, copper, or any combination or composite of aluminum, copper, or stainless steel.

[0110] In some embodiments, the adhesive layer 408 can be a thin layer of chromium (Cr). Alternatively, the adhesive layer 408 can be a thin layer of gold, nickel, titanium, or tantalum. The adhesive layer 408 can be disposed between the conductive substrate 406 and the active electrode layer 132.

[0111] As described above, the active electrode layer 132 can be deposited directly on the conductive substrate 406 without the adhesive layer 408.

[0112] The active electrode layer 132 can have a thickness 410 of the active electrode layer of about 50 nm to 500 nm (for example, about 400 nm). The adhesive layer 408 can have a thickness 412 of the adhesive layer of about 5 nm to 50 nm (for example, about 20 nm). The ratio of the thickness 412 of the adhesive layer to the thickness 410 of the active electrode layer can be about 1:10 to 1:20.

[0113] The conductive substrate 406 can have a thickness 414 of the substrate layer. The thickness of the substrate layer can be about 10 μm to 0.70 mm (for example, about 0.61 mm).

[0114] FIG. 4D is a side view showing an exemplary active sensor 106 used for measuring the pH of a sample. In this embodiment, surface modification techniques can be used to modify the platinum layer 416. For example, oxygen plasma treatment can be used to oxidize the platinum layer 416 to form a platinum oxide / platinum dioxide (PtO2) layer 418. The platinum oxide layer 418 thus formed can react with hydrogen ions and can be used as a highly pH-sensitive layer. Thus, the platinum oxide layer 418 can function as the active electrode layer 132.

[0115] The platinum layer 416 can be adhered to the conductive substrate 406 via the adhesive layer 408. The conductive substrate 406 can be formed of a conductive material such as stainless steel (SS). For example, the conductive substrate can be SS316. In other embodiments, the conductive substrate 406 can be formed of aluminum, copper, or any combination or composite of aluminum, copper, or stainless steel.

[0116] In some embodiments, the adhesive layer 408 can be a thin layer of chromium (Cr). Alternatively, the adhesive layer 408 can be a thin layer of gold, nickel, titanium, or tantalum. The adhesive layer 408 can be disposed between the conductive substrate 406 and the active electrode layer 132.

[0117] In an alternative embodiment, the platinum layer 416 can be deposited directly on one side of the conductive substrate 406 without the adhesive layer 408.

[0118] The platinum layer 416 can have a layer thickness of about 50 nm to 500 nm (e.g., about 400 nm). The adhesive layer 408 can have an adhesive layer thickness 412 of about 5 nm to 50 nm (e.g., about 20 nm).

[0119] The conductive substrate 406 can have a substrate layer thickness 414. The substrate layer thickness can be about 10 μm to 0.70 mm (e.g., about 0.61 mm).

[0120] The platinum oxide layer 418 can have an oxide layer thickness 420. The oxide layer thickness 420 can be about 10 nm to 100 nm.

[0121] As described above, a deposition layer can be selected to obtain a certain desired sensitivity or specificity for a particular analyte. Also, other surface modification techniques such as self-assembled monolayers (SAMs), antibodies, binding antibody fragments, binding aptamers, biofunctionalization with binding DNA, and plasma treatment can be employed to change the surface properties of the deposition layer and thereby adjust the specificity and sensitivity.

[0122] FIG. 5A is a side view showing an active sensor 106 according to yet another example. This embodiment of the active sensor 106 utilizes the scale and efficiency of printed circuit board (PCB) manufacturing techniques.

[0123] The active sensor 106 can be formed of a non-conductive PCB substrate 500 partially covered by an active electrode layer 132. In some embodiments, the non-conductive PCB substrate 500 can be formed of polyimide. In other embodiments, the non-conductive PCB substrate 500 can be formed of a glass-reinforced epoxy laminate material such as FR-4 composite material. In certain embodiments, the PCB substrate 500 can be a flexible PCB material.

[0124] In some embodiments, the active electrode layer 132 can be formed of a noble metal. For example, the active electrode layer 132 can be formed of platinum (see, for example, FIGS. 5A, 5B, and 6A - 6C), gold (see, for example, FIGS. 6A - 6C), or a combination or composite thereof. Platinum or gold can be deposited on the PCB substrate 500 by electrodeposition or sputtering.

[0125] The active electrode layer 132 can have a thickness of at least 50 nm for the active electrode layer. In certain embodiments, the active electrode layer 132 can have a thickness of at least 400 nm for the active electrode layer. When the active electrode layer 132 is formed of platinum, the active sensor 106 can be used for measuring or monitoring the ORP of a sample.

[0126] In an alternative embodiment, a platinum layer deposited on the non - conductive PCB substrate 500 can be modified by a surface modification technique to make the platinum layer a highly pH - sensitive layer (see, for example, FIG. 4D). For example, oxygen plasma treatment can be used to oxidize the platinum layer to form a platinum oxide (PtO2) layer. The platinum oxide layer thus formed can react with hydrogen ions and can be used as a highly pH - sensitive layer. In this embodiment, the active sensor 106 can be used for measuring or monitoring the pH of a sample.

[0127] The PCB substrate 500 can have a conductive contact or a conductive contact layer 502 patterned on the substrate side surface opposite to the active electrode layer 132. In some embodiments, the conductive contact layer 502 can be a gold layer. In other embodiments, the conductive contact layer 502 can be formed of another type of conductive metal such as platinum, nickel, copper, or an alloy or composite thereof.

[0128] As shown in FIG. 5A, the active electrode layer 132 can be electrically coupled to a conductive contact or a conductive contact layer 502 by one or more conductive vias 504. In one embodiment, the conductive via 504 can be partially formed of copper or a copper alloy. In other embodiments, the conductive via 504 can be formed of another type of conductive metal such as gold.

[0129] In some embodiments, each active sensor 106 can have at least one conductive via 504 disposed at the center of the sensor package. In other embodiments, the conductive via 504 can be disposed near the outer periphery or edge of the sensor package.

[0130] The conductive vias 504 can be formed by electroplating, vapor deposition, or a combination thereof. Additionally, standard PCB etching processes can be used to form additional features or patterns on the PCB substrate 500.

[0131] FIG. 5B shows a single PCB substrate covered with an active electrode layer 132 (e.g., platinum) that can be diced into a plurality of individual active sensors 106. For example, a single PCB substrate can be diced to produce 400 to 500 active sensors 106.

[0132] FIG. 6A is a black and white image showing an active sensor 106 consisting of three individual active electrodes including a gold (Au) active electrode 600A, a first platinum (Pt) active electrode 600B, and a second platinum active electrode 600C. The active sensor 106 can be manufactured using the PCB manufacturing techniques described above. The only difference is that different active electrode materials (e.g., Au and Pt) are electroplated or vapor deposited on the same non-conductive PCB substrate 500. For example, one section or strip of the non-conductive PCB substrate 500 can be covered by a first active electrode material or layer (e.g., Au), and another section or strip of the same non-conductive PCB substrate 500 can be covered by a second active electrode material or layer (e.g., Pt).

[0133] As shown in FIG. 6A, the active sensor 106 can be coupled (e.g., adhered or insert molded) to a portion of the chamber sidewall 112 of the sample chamber 108. Since the sample container 104 shown in FIG. 6A is formed as a transparent container, the active electrode side of the active sensor 106 can be visually recognized through the transparent wall of the sample chamber 108. When the sample chamber 108 is filled with a fluid sample (not shown in FIG. 6A), the fluid sample can contact the gold active electrode 600A, the first platinum active electrode 600B, and the second platinum active electrode 600C through the window opening 114 formed along the chamber sidewall 112.

[0134] One advantage of the active sensor 106 consisting of a plurality of active electrodes is that each electrode can report a unique potential with respect to the same reference electrode or reference sensor (e.g., reference sensor 122). Further, the active electrodes can be formed of different materials so as to be able to simultaneously measure or monitor different solution characteristics (e.g., ORP and pH) of the sample.

[0135] Although not shown, it is contemplated by the present disclosure that an active sensor 106 formed by arranging a plurality of active electrodes as an active electrode array (e.g., electrode array 96) can be integrally formed in one sensor device 100 to simultaneously measure a plurality of solution characteristics of the sample. The plurality of active electrodes can be patterned on the non-conductive PCB substrate 500 using techniques common in the PCB industry, including selective etching, photoresist layers, shadow masking, or combinations thereof.

[0136] FIG. 6B is a black and white image showing an enlarged view of the contact side of the active sensor 106 shown in FIG. 6A. For example, as shown in FIG. 6B, each of the active electrodes can have its own conductive contact strip 602 or segment deposited or plated on the opposite side of the non-conductive PCB substrate 500. For example, the conductive contact strip 602 or segment can be formed of gold. The conductive contact strip 602 or segment can be a segmented case of the conductive contact layer 502 (see, for example, FIG. 5A). The active electrode can be electrically coupled to the conductive contact by a conductive via (not shown in FIG. 6B) extending through the non-conductive PCB substrate 500.

[0137] FIG. 6C is a black and white image showing one PCB substrate that can be segmented into individual active sensors 106 (see, for example, FIGS. 6A and 6B). As described above, the non-conductive PCB substrate can be covered on one side by the active electrode layer 132 using electroplating or sputter deposition. The other side of the PCB substrate can be partially covered by the conductive contact layer 502 (similarly via electroplating or deposition techniques). The active electrode layer 132 can be electrically coupled to the conductive contact layer 502 by a conductive via 504 extending through the non-conductive PCB substrate. As described above, one PCB substrate processed in this way can be segmented to manufacture 400 to 500 active sensors 106.

[0138] FIG. 7 is a diagram showing an active sensor 106 according to yet another example, formed by covering a non-conductive polymer substrate 700 constituting the through-hole 702 with the active electrode layer 132 and the conductive contact layer 502.

[0139] The non-conductive polymer substrate 700 can be a substrate formed of any type of injection molding plastic such as polyamide, polycarbonate, polyoxymethylene, polystyrene, acrylonitrile-butadiene-styrene, polypropylene, polyethylene, or their copolymers or mixtures.

[0140] In some embodiments, the active electrode layer 132 is a noble metal layer. For example, the active electrode layer 132 can be a layer of platinum, a layer of gold, or a combination or composite thereof. The platinum layer or the gold layer can be deposited or otherwise applied to the conductive polymer substrate 700 via sputter deposition (e.g., physical vapor deposition (PVD) sputter deposition), vapor deposition, or electrodeposition. In some embodiments, the platinum layer or the gold layer can be printed using screen printing.

[0141] The active electrode layer 132 can have an active electrode layer thickness of at least 50 nm. In certain embodiments, the active electrode layer 132 can have an active electrode layer thickness of at least 400 nm. When the active electrode layer 132 is formed from platinum or gold, the active sensor 106 can be used to measure or monitor the ORP of a sample.

[0142] In an alternative embodiment, the platinum layer deposited on the non-conductive polymer substrate 700 can be modified with a surface modification technique to make the platinum layer a highly pH-sensitive layer (see, e.g., FIG. 4D). For example, oxygen plasma treatment can be used to oxidize the platinum layer to form a platinum oxide (PtO2) layer. The platinum oxide layer thus formed can react with hydrogen ions and can be used as a highly pH-sensitive layer. In this embodiment, the active sensor 106 can be used to measure or monitor the pH of a sample.

[0143] In some embodiments, the conductive contact layer 502 can be a gold layer. In other embodiments, the conductive contact layer 502 can be formed of another type of conductive metal such as platinum, nickel, copper, or an alloy or composite thereof.

[0144] The through-hole 702 can have a diameter of about 10 μm to 100 μm. In some embodiments, the active sensor 106 can have a width dimension of about 100 μm to 6.0 mm and a length dimension of about 100 μm to 6.0 mm. For example, the active sensor 106 can have a width dimension of about 100 μm and a length dimension of about 100 μm.

[0145] Figures 8A and 8B are side cross-sectional views showing two different embodiments of the active sensor 106. In either embodiment, the ends of the through-hole 702 are covered by the active electrode layer 132 and the conductive contact layer 502. As shown in Figures 8A and 8B, the conductive coating can cover the lateral sides of the through-hole 702.

[0146] In the embodiment shown in Figure 8A, the conductive coating is composed of the same material as the active electrode layer 132. In the embodiment shown in Figure 8B, the conductive coating is composed of the same material as the conductive contact layer 502. Whether the lateral sides of the through-hole 702 are covered by the active electrode material or the conductive coating material can be determined by which layer is deposited first on the non-conductive polymer substrate 700.

[0147] As a more specific example, when the active electrode layer 132 is a layer of platinum and the layer of platinum is deposited first on the non-conductive polymer substrate 700, the conductive coating covering the lateral sides of the through-hole can be a platinum coating. Alternatively, when the conductive contact layer 502 is a layer of gold and the layer of gold is deposited first on the non-conductive polymer substrate 700, the conductive coating covering the lateral sides of the through-hole can be a gold coating.

[0148] In some embodiments (e.g., as shown in FIGS. 8A and 8B), as long as the lateral sides of the through-hole 702 are covered by a conductive coating, it is not necessary to fill the entire through-hole 702. The conductive coating can function as an electrical connection or conductive path between two sides of the active sensor 106. Alternatively, at least a part of the through-hole 702 may be filled with a conductive coating.

[0149] In some embodiments, the non-conductive polymer substrate 700 can start as a plastic sheet having an array of small through-holes 702 formed throughout the plastic sheet. The plastic sheet can subsequently be first covered with the active electrode layer 132 or the conductive contact layer 502. At least one of the lateral sides of the through-hole 702 and the ends of the through-hole 702 can subsequently be coated with the material used to first cover the plastic sheet. The other side of the plastic sheet including the remaining open ends of the through-hole 702 can subsequently be covered with the conductive contact layer 502 or the active electrode layer 132, depending on which layer went on first. Once both sides of the plastic sheet are covered, the plastic sheet can be singulated to manufacture individual active sensors 106. The active sensors 106 manufactured in this way can be formed in a small size of 100 μm × 100 μm (W × L).

[0150] FIG. 9 shows that a large sheet of non-conductive plastic or a large PCB can be processed (covered with an active electrode layer, an adhesive layer, a conductive layer, or a combination thereof) using the methods disclosed herein and subsequently singulated into a plurality of active sensors 106. In some embodiments, the large sheet of non-conductive plastic or the large PCB can be singulated using sawing, laser cutting, metal shearing, hot wire cutting, die cutting, stamping, or a combination thereof.

[0151] FIG. 10 is a side view showing a sensor device 100 according to another example, including an active sensor 106 formed from a conductive stud 1000. In some embodiments, the conductive stud 1000 can be a stainless steel stud. The conductive stud 1000 can be partially covered by an active electrode layer 132 that extends into the chamber cavity 109. The portion of the conductive stud 1000 covered by the active electrode layer 132 can extend into the chamber cavity 109 such that a sample in the chamber cavity 109 can be in fluid contact with the active electrode layer 132.

[0152] The conductive stud 1000 can be coupled to at least a portion of the chamber sidewall 112 at a window opening formed along the chamber sidewall 112. The opposite end of the conductive stud 1000 (the end not covered by the active electrode layer 132) can extend outside the chamber sidewall 112 and contact one or more conductive connections of the leader device 190. The conductive stud 1000 can be substantially formed as a cylinder with a rounded edge.

[0153] The conductive stud 1000 can be insert molded or adhered to the chamber sidewall 112 with an adhesive.

[0154] In some embodiments, the active electrode layer 132 is a noble metal layer. For example, the active electrode layer 132 can be a layer of platinum, a layer of gold, or a combination or composite thereof. The platinum layer or gold layer can be deposited or otherwise applied to the conductive stud 1000 via sputter deposition (e.g., physical vapor deposition (PVD) sputter deposition), vapor deposition, or electroplating.

[0155] The active electrode layer 132 can have a thickness of at least 50 nm for the active electrode layer. In certain embodiments, the active electrode layer 132 can have a thickness of at least 400 nm for the active electrode layer. When the active electrode layer 132 is formed from platinum or gold, the active sensor 106 can be used to measure or monitor the ORP of a sample.

[0156] In an alternative embodiment, the platinum layer deposited on the conductive stud 1000 can be modified by a surface modification technique to make the platinum layer a highly pH-sensitive layer. For example, oxygen plasma treatment can be used to oxidize the platinum layer to form a platinum oxide (PtO2) layer. The platinum oxide layer thus formed reacts with hydrogen ions and can be used as a highly pH-sensitive layer. In this embodiment, the active sensor 106 can be used to measure or monitor the pH of a sample.

[0157] FIG. 11 is a graph showing the change over time of the oxidation-reduction potential (ORP) of three samples containing Escherichia coli ATCC25922 measured using three types of sensors. As shown in FIG. 11, one sensor is a conventional ORP probe commonly used at the diagnosis site (for example, a commercially available ORP probe sold by Mettler-Toledo, LLC). The other two sensors are embodiments of the sensor device 100 disclosed herein, one having an active sensor 106 composed of a platinum active electrode layer deposited by vapor deposition, and the other having an active sensor 106 composed of an electroplated platinum active electrode layer. The active sensor 106 in any of the embodiments is coupled to at least a part of the chamber sidewall 112 at the window opening 114 formed along the chamber sidewall 112. In these embodiments, the active sensor 106 is positioned so that no part of the active sensor 106 extends into the chamber cavity 109 of the sample chamber 108. The change in ORP when each of the two sensor devices 100 was placed in the reader device 190 was measured by the reader device 190.

[0158] As shown by the three Escherichia coli growth curves, the two sensor devices 100 showed performance similar to that of a commercially available ORP probe. The variation in signal response was within an acceptable range.

[0159] FIG. 12 is a graph showing the change over time in pH of four samples containing different starting concentrations of Escherichia coli ATCC 25922, using the sensor device 100 disclosed herein having an active sensor 106 that includes a tantalum oxide / tantalum pentoxide (Ta2O5) active electrode layer.

[0160] As shown in FIG. 12, the measured growth curve of Escherichia coli shows a classical growth pattern where the bacteria first have a lag phase and then reach the stationary phase after a logarithmic phase. The pattern and shape of the curve are due to the cell activity of the active Escherichia coli in the sample.

[0161] FIG. 13A is a perspective view showing a reader device 190 configured to measure the solution characteristics of a sample within the sample chamber 108 of the sensor device 100. The reader device 190 is capable of measuring the solution characteristics of the sample based on the potential difference measured between the active sensor 106 (more specifically, the active electrode layer 132) and the reference sensor 122 (more specifically, the reference electrode material 149) when the active sensor 106 and the reference sensor 122 are electrically coupled via a conductive connection or interface within the reader device 190. The reader device 190 can function as a voltmeter or another type of high-impedance amplifier or source meter for measuring the relative change in the equilibrium potential at the interface between electrode layers in fluid contact with a sample containing electroactive redox species or charged ions.

[0162] The growth and metabolism (or lack thereof) of infectious pathogens within the sample can change the amount of electroactive redox species and the amount of H + ions, and thus the solution characteristics of the sample can change. For example, as a result of cell activity by infectious pathogens, the amount of electroactive redox species in the sample can change. As a more specific example, the growth and metabolism (or lack thereof) of infectious pathogens within the sample can change the amount of energy carriers such as nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FADH2), and thus the amount of oxygen and the amount of electron donors can also change.

[0163] When the active electrode layer 132 of the sensor device 100 is formed of a material highly sensitive to the oxidation-reduction potential (ORP), such as platinum (Pt) or gold (Au), the reader device 190 can measure the oxidation-reduction potential (ORP) of the sample. Further, the reader device 190 can also measure the pH of the sample when the active electrode layer 132 of the sensor device 100 is formed of a material highly sensitive to pH, such as a metal oxide layer.

[0164] FIG. 13A illustrates that the reader device 190 can consist of a reader housing 1300 configured to accommodate specific functional elements of the reader device 190, including a main control device 1301 (see, for example, FIG. 13C), a signal readout control unit 1303 (see FIGS. 14, 15A, and 15B), a thermal control module 1305 (see, for example, FIGS. 13B, 13C, and 13D), and an aeration control module 1307 (see, for example, FIGS. 13B and 13C). Also, the reader housing 1300 can expose a touch screen display 1302 configured to display measurement results and allow a user to input commands to the reader device 190.

[0165] The lid 1304 or cover of the reader device 190 can be opened or lifted to expose a container receiving space 1306 (see, for example, FIG. 13B) configured to receive or hold the sensor device 100 for analysis or investigation by the reader device 190.

[0166] FIG. 13B is a partial cut-away view showing the leader device 190 with the sensor device 100 filled with a sample loaded therein. When the sensor device 100 is positioned within the container receiving space 1306, the reference electrode contact 1308 of the leader device 190 is arranged or movable to contact the reference electrode material 149 positioned on the container cap 116 of the sensor device 100 (see, e.g., FIG. 1D). Further, when the sensor device 100 is positioned within the container receiving space 1306, the active electrode contact 1310 of the leader device 190 is arranged or movable to contact the conductive substrate layer or conductive contact of the active sensor 106 (e.g., either the conductive substrate 406 of FIGS. 4B through 4D or the conductive contact layer 502 of FIG. 5A).

[0167] In some embodiments, the reference electrode contact 1308 and the active electrode contact 1310 can be composed of one or more conductive pogo pins or spring-loaded pins, conductive leaf contacts, or combinations thereof. More specifically, the pogo pins or leaf contacts having conductivity can be formed of copper, nickel, stainless steel, or alloys thereof.

[0168] The reference electrode contact 1308 and the active electrode contact 1310 can be electrically coupled to the signal readout control unit 1303. The signal readout control unit 1303 can be composed of one or more processors, chip sets, or chip modules programmed to convert and read out the signals obtained from the active sensor 106 and the reference sensor 122 of the sensor device 100.

[0169] In addition, FIG. 13B is a diagram illustrating that the leader device 190 can be composed of a heat control module 1305 and an aeration control module 1307. The heat control module 1305 can be configured to perform culturing in the sensor device 100 filled with a sample. The heat control module 1305 can culture in the sensor device 100 by heating at least a part of the sensor device 100 via a heating block 1318 (see, for example, FIG. 13D). In some embodiments, the heating block 1318 can heat the lateral side of the sample chamber 108 facing the active sensor 106. In a specific embodiment, the heating block 1318 can partially surround the sample chamber 108 or be placed like a cradle to heat the sensor device 100.

[0170] In some embodiments, a part of the heating block 1318 can be formed of aluminum. In other embodiments, a part of the heating block 1318 can be formed of another type of thermally conductive metal material.

[0171] The sensor device 100 can be heated to a culturing temperature of about 30°C to 40°C (for example, about 35°C plus or minus 2°C). The sensor device 100 can be cultured during the culturing period. The culturing period can be in the range of 15 minutes to more than 48 hours. The culturing period can be adjusted according to the type of suspected infectious pathogen in the sample.

[0172] In some embodiments, the heat control module 1305 can be controlled by the main control device 1301 (see, for example, FIG. 13C) of the leader device 190. In other embodiments, the heat control module 1305 can be controlled by another control device or module within the leader device 190, or by the signal reading control unit 1303.

[0173] In some embodiments, before being cultured in the sensor device 100, a nutrient solution or a stimulation solution can be introduced into the sample chamber 108. For example, the nutrient solution can be a solution containing bacteriotryptone, yeast extract, beef extract, cation-adjusted Mueller-Hinton broth (CAMHB), starch, acid hydrolysate of casein, calcium chloride, magnesium chloride, sodium chloride, blood or hemolyzed horse serum (LHB), a hemolyzed CAMHB-LHB mixture, glucose, or a combination thereof. When the sample is composed of a body fluid, the nutrient solution can be used to counteract the buffering effect of ions and substances contained in the sample.

[0174] The aeration control module 1307 can be configured to aerate the sample in the sample chamber 108 by pumping a gas 162 (e.g., see FIG. 1D) into the chamber cavity 109 containing the sample. The gas 162 can be pumped into the sample chamber 108 through an aeration port 160 formed along the bottom of the sample chamber 108 (e.g., see FIG. 1D).

[0175] By aerating the sample, the amount of oxygen supplied to the infectious pathogens in the sample can be increased, and the growth rate of the infectious pathogens can be reliably enhanced. Furthermore, by aerating the sample, it is also possible to detach the infectious pathogens from the inner wall of the sample chamber 108 so as to suppress the formation of biofilms.

[0176] FIG. 13C is a perspective view showing a part of the reader device 190 with the reader housing 1300 removed. As shown in FIG. 13C, the aeration control module 1307 can deliver the gas 162 through a gas delivery conduit 1312 that connects the aeration control module 1307 to the sensor device 100. In some embodiments, at least one section of the gas delivery conduit 1312 can be positioned along or wound around the base or bottom of the reader device 190.

[0177] FIG. 13D is an enlarged view showing a mode in which a gas nozzle 1314 is connected to the bottom of the sensor device 100 to aerate the sample in the sample chamber 108. The gas nozzle 1314 may be disposed at the end or distal end of the gas delivery conduit 1312.

[0178] As shown in FIG. 13D, the gas nozzle 1314 can be connected to an aeration port 160 at the bottom of the sample chamber 108 via a nozzle interface 1316. In some embodiments, the nozzle interface 1316 can be an O-ring. In other embodiments, the nozzle interface 1316 can be another type of gasket or fluid sealing interface.

[0179] In some embodiments, the gas 162 can be ambient air (e.g., air within a laboratory, clinical environment, or test facility). In other embodiments, the gas 162 can consist of a combination of pressurized oxygen, carbon dioxide, nitrogen, and argon. By aerating the sample, an oxygen-rich environment can be provided within the sample chamber 108, thereby accelerating the growth of the microbial population within the sample.

[0180] The aeration control module 1307 can pump the gas 162 into the sample chamber 108 at a constant flow rate of about 1.0 mL / min to 10.0 mL / min.

[0181] In some embodiments, the aeration control module 1307 can be controlled by the main control device 1301 (see, e.g., FIG. 13C). In other embodiments, the aeration control module 1307 can be controlled by another control device or module within the reader device 190, or by the signal reading control unit 1303. For example, the amount of gas 162 (e.g., ambient air) pumped or directed into the sample chamber 108 can be indicated by changes in the solution characteristics of the sample detected by the reader device 190, or by the absence of such changes.

[0182] FIG. 14 is a diagram showing a manufacturing method 1400 of a sensor device 100 for measuring the solution characteristics of a sample. The method 1400 can include, in step 1402, cleaning the conductive substrate 406 (e.g., a sheet of stainless steel such as 316SS) by acid and base treatment.

[0183] The conductive substrate 406 can first be cleaned by a series of acid and base treatments to remove impurities or surface contaminants (e.g., free iron). Such treatments can be performed with nitric acid (10%) followed by ammonium hydroxide (175 mM), isopropyl alcohol (99%) or acetone. In other embodiments, the conductive substrate 406 can be cleaned using other acids, bases, alcohols, solvents, or other chemicals to remove scale.

[0184] The method 1400 can further include, in step 1404, depositing an adhesive material on one side of the cleaned conductive substrate 406 until an adhesive layer 408 is formed on the cleaned conductive substrate 406. In some embodiments, the adhesive layer 408 can be deposited by a sputter deposition technique such as physical vapor deposition (PVD). In some embodiments, the adhesive layer 408 can be a layer of chromium (Cr). Chromium can be selected because it forms a bond with the chromium contained in the stainless steel of the conductive substrate 406. In other embodiments, the adhesive layer 408 can also be a layer of gold (Au) or nickel (Ni).

[0185] Step 1404 can also include depositing an adhesive material (e.g., Cr, Au, or Ni) until the thickness of the adhesive layer 408 is at least 20 nm.

[0186] Method 1400 can further include depositing an active electrode material on the adhesive layer 408 until an active electrode layer 132 is formed on the adhesive layer 408 in step 1406. The active electrode layer 132 can be a noble metal layer such as a platinum layer or a gold layer when the sensor device 100 is used as an ORP sensor. The step of depositing the active electrode layer 132 can include depositing an active electrode material (e.g., Pt) using sputter deposition (e.g., PVD), vapor deposition method, or electrodeposition. In certain processes such as the vapor deposition method, the conductive substrate 406 can be pre-cleaned by argon (Ar) plasma etching in a vacuum. In other embodiments, the active electrode material can be applied using ink screen printing.

[0187] Step 1406 can also include depositing the active electrode material until the active electrode layer 132 has a thickness of at least 50 nm. Step 1406 can further include depositing the active electrode material until the active electrode layer 132 has a thickness of at least 400 nm. The applicant has discovered that this minimum thickness is necessary to prevent the formation of nano-sized holes in the active electrode layer 132 through which the fluid (e.g., fluid sample) passes and contacts other layers of the active sensor 106, thereby adversely affecting the measurement. Further, when an antibacterial material (e.g., copper or nickel) is used as the conductive substrate 406, the active electrode layer 132 having a thickness of at least 400 nm can function as a barrier to protect microorganisms in the fluid sample.

[0188] In certain embodiments, the adhesive layer 408 can be deposited in a vacuum chamber, and the active electrode layer 132 can be deposited in the same vacuum chamber following the adhesive layer 408.

[0189] Alternatively, step 1406 can include depositing a metal layer, surface modifying the metal layer, and forming a metal oxide layer. For example, step 1406 can include depositing a platinum layer and oxidizing the platinum layer to form a platinum oxide (PtO2) layer that functions as the active electrode layer 132. The active electrode layer 132 can be a metal oxide layer (e.g., platinum oxide or tantalum oxide) when the sensor device 100 is used as a pH sensor.

[0190] Method 1400 can further include, in step 1408, singulating the conductive substrate 406 covered by the adhesive layer 408 and the active electrode layer 132. The conductive substrate 406 covered by the adhesive layer 408 and the active electrode layer 132 can be singulated by laser cutting, metal shearing, hot wire cutting, die cutting, stamping, or saw cutting. The conductive substrate 406 covered by the adhesive layer 408 and the active electrode layer 132 can be singulated to obtain an active sensor 106 sized to cover a window opening 114 formed along the chamber sidewall 112 of the sample chamber 108 (see, e.g., FIGS. 1B-1D and 2).

[0191] Method 1400 may further include, at step 1410, coupling the active sensor 106 to at least a portion of the chamber sidewall 112. The active sensor 106 may be coupled to at least a portion of the chamber sidewall 112 such that no portion of the active sensor 106 extends into the chamber cavity 109 within the sample chamber 108, and the active electrode layer 132 faces the chamber cavity 109 such that any sample within the chamber cavity 109 can be in fluid contact with the active electrode layer 132 through at least a portion of the chamber sidewall 112 surrounding the window opening 114. The active sensor 106 may be coupled to at least a portion of the chamber sidewall 112 such that the active sensor 106 (including the active electrode layer 132) is positioned radially outward from the side facing the inside of the chamber sidewall 112 or the side facing the cavity, and the lateral side 136 of the active sensor 106 is not in fluid communication with the chamber cavity 109.

[0192] In some embodiments, the step of coupling the active sensor to at least a portion of the chamber sidewall 112 of the sample chamber 108 may further include applying a bead of adhesive 138 to a portion of the chamber sidewall 112 within a recess 134 formed along the chamber sidewall 112 surrounding the window opening 114, pressing or placing the active sensor 106 onto the bead of adhesive 138 within the recess 134, and curing the adhesive 138.

[0193] In an alternative embodiment, the step of coupling the active sensor to at least a portion of the chamber sidewall 112 of the sample chamber 108 may include insert molding the active sensor 106 into the chamber sidewall 112 while the sample chamber 108 is being formed by injection molding.

[0194] In a further alternative embodiment, the step of coupling the active sensor to at least a portion of the chamber sidewall 112 of the sample chamber 108 may include locally melting (e.g., by ultrasonic welding) a portion of the chamber sidewall 112 surrounding the window opening 114, pressing or disposing the active sensor 106 onto the melted portion of the chamber sidewall 112, and cooling the melted portion of the chamber sidewall 112 to affix the active sensor 106 to the chamber sidewall 112.

[0195] FIG. 15 is a diagram showing yet another method 1500 of manufacturing a sensor device 100 for measuring solution characteristics of a sample. Method 1500 can include, at step 1502, providing a non-conductive printed circuit (PCB) substrate 500 (see, e.g., FIG. 5A).

[0196] Method 1500 can further include depositing an active electrode material on one side of the non-conductive PCB substrate 500 until an active electrode layer 132 is formed on the non-conductive PCB substrate 500 at step 1504. Step 1504 can further include depositing the active electrode material until the active electrode layer 132 has a thickness of at least 50 nm. Step 1504 can further include depositing the active electrode material until the active electrode layer 132 has a thickness of at least 400 nm. The active electrode layer 132 can be electrically coupled to a conductive contact or conductive contact layer 502 of the non-conductive PCB substrate 500 by a conductive via 504 extending through the non-conductive PCB substrate 500 after the deposition step.

[0197] The active electrode layer 132 can be a noble metal layer such as a platinum layer or a gold layer when the sensor device 100 is used as an ORP sensor. The step of depositing the active electrode layer 132 can include depositing an active electrode material (e.g., Pt) using sputter deposition (e.g., PVD), evaporation deposition, or electrodeposition.

[0198] Method 1500 may further include, at step 1506, fragmenting a non-conductive PCB substrate 500 covered by an active electrode layer 132 to obtain an active sensor 106 sized to cover a window opening 114 formed along a chamber sidewall 112 of a sample chamber 108. The non-conductive PCB substrate 500 covered by the active electrode layer 132 can be fragmented by laser cutting, metal shearing, hot wire cutting, die cutting, stamping, or saw cutting. The active sensor 106 can consist of at least one conductive via 504 extending through the PCB substrate 500.

[0199] Method 1500 may further include, at step 1508, coupling the active sensor 106 to at least a portion of the chamber sidewall 112. The active sensor 106 can be coupled to at least a portion of the chamber sidewall 112 such that no portion of the active sensor 106 extends into the chamber cavity 109 within the sample chamber 108, and the active electrode layer 132 faces the chamber cavity 109 such that any sample within the chamber cavity 109 can be in fluid contact with the active electrode layer 132 through at least a portion of the chamber sidewall 112 surrounding the window opening 114. The active sensor 106 can be coupled to at least a portion of the chamber sidewall 112 such that the active sensor 106 (including the active electrode layer 132) is positioned radially outward from the side facing the inside or the cavity of the chamber sidewall 112, and the lateral side surface 136 of the active sensor 106 is not in fluid communication with the chamber cavity 109.

[0200] In some embodiments, the step of coupling the active sensor to at least a portion of the chamber sidewall 112 of the sample chamber 108 may further include applying a bead of adhesive 138 to a portion of the chamber sidewall 112 within a recess 134 formed along the chamber sidewall 112 surrounding the window opening 114, pressing or placing the active sensor 106 onto the bead of adhesive 138 within the recess 134, and curing the adhesive 138.

[0201] In an alternative embodiment, the step of coupling the active sensor to at least a portion of the chamber sidewall 112 of the sample chamber 108 may include the step of insert molding the active sensor 106 into the chamber sidewall 112 while forming the sample chamber 108 by injection molding.

[0202] In a further alternative embodiment, the step of coupling the active sensor to at least a portion of the chamber sidewall 112 of the sample chamber 108 may include the steps of locally melting (e.g., by ultrasonic welding) a portion of the chamber sidewall 112 surrounding the window opening 114, pressing or placing the active sensor 106 onto the melted portion of the chamber sidewall 112, and cooling the melted portion of the chamber sidewall 112 to affix the active sensor 106 to the chamber sidewall 112.

[0203] FIG. 16 is a diagram showing yet another further method 1600 of manufacturing a sensor device 100 for measuring solution characteristics of a sample. The method 1600 can include, at step 1602, providing a non-conductive polymer substrate 700 including a plurality of through-holes 702. The method 1600 can further include, at step 1604, depositing a conductive contact layer 502 on one side of the polymer substrate 700. The step of depositing the conductive contact layer 502 can include depositing a conductive material (e.g., Au) on the polymer substrate 700 using sputter deposition (e.g., PVD), evaporation deposition, or electrodeposition.

[0204] The method 1600 can further include, at step 1606, depositing an active electrode layer 132 on another surface of the polymer substrate 700. The step of depositing the active electrode layer 132 can include depositing an active electrode material (e.g., Pt) on the polymer substrate 700 using sputter deposition (e.g., PVD), evaporation deposition, or electrodeposition.

[0205] One end of each of the through-holes 702 can be covered by the active electrode layer 132, and the other end of each of the through-holes 702 can be covered by the conductive contact layer 502. After the deposition step, the active electrode layer 132 can be electrically coupled to the conductive contact layer 502 via a conductive coating that covers the lateral sides of the through-holes 702.

[0206] Method 1600 can further include, at step 1608, fragmenting a non-conductive polymer substrate 700 covered by the active electrode layer 132 and the conductive contact layer 502 to obtain an active sensor 106 sized to cover a window opening 114 formed along a chamber sidewall 112 of the sample chamber 108. The non-conductive polymer substrate 700 covered by the active electrode layer 132 and the conductive contact layer 502 can be fragmented by laser cutting, metal shearing, hot wire cutting, die cutting, stamping, or saw cutting. The active sensor 106 can include at least one through-hole 702 extending through the non-conductive polymer substrate 700.

[0207] Method 1600 can further include, at step 1610, coupling the active sensor 106 to at least a portion of the chamber sidewall 112. The active sensor 106 can be coupled to at least a portion of the chamber sidewall 112 such that no portion of the active sensor 106 extends into the chamber cavity 109 within the sample chamber 108, and the active electrode layer 132 faces the chamber cavity 109 such that any sample within the chamber cavity 109 can be in fluid contact with the active electrode layer 132 through at least a portion of the chamber sidewall 112 surrounding the window opening 114. The active sensor 106 can be coupled to at least a portion of the chamber sidewall 112 such that the active sensor 106 (including the active electrode layer 132) is positioned radially outward from the side facing the inside of the chamber sidewall 112 or the side facing the cavity, and the lateral sides 136 of the active sensor 106 are not in fluid communication with the chamber cavity 109.

[0208] In some embodiments, the step of coupling the active sensor to at least a portion of the chamber sidewall 112 of the sample chamber 108 can further include applying a bead of adhesive 138 to a portion of the chamber sidewall 112 within a recess 134 formed along the chamber sidewall 112 surrounding the window opening 114, pressing or placing the active sensor 106 onto the bead of adhesive 138 within the recess 134, and curing the adhesive 138.

[0209] In an alternative embodiment, the step of coupling the active sensor to at least a portion of the chamber sidewall 112 of the sample chamber 108 can include insert molding the active sensor 106 into the chamber sidewall 112 while the sample chamber 108 is being formed by injection molding.

[0210] In a further alternative embodiment, the step of coupling the active sensor to at least a portion of the chamber sidewall 112 of the sample chamber 108 can include locally melting (e.g., by ultrasonic welding) a portion of the chamber sidewall 112 surrounding the window opening 114, pressing or placing the active sensor 106 onto the melted portion of the chamber sidewall 112, and cooling the melted portion of the chamber sidewall 112 to affix the active sensor 106 to the chamber sidewall 112.

[0211] Multiple embodiments have been described. Nevertheless, it will be understood by those skilled in the art that various changes and modifications can be made to the present disclosure without departing from the spirit and scope of the embodiments. The elements of the systems, devices, apparatuses, and methods shown with any embodiment are illustrative of a particular embodiment and can be combined with or otherwise used in other embodiments within the present disclosure. For example, the steps of any method depicted in the figures or described in the present disclosure do not require the particular order or sequential order shown or described to achieve the desired result. Additionally, other step operations may be provided or steps or operations may be deleted or omitted from the described method or process to obtain the desired result. Further, any component or part of any device or system described in the present disclosure or depicted in the figures may be removed, deleted, or omitted to achieve the desired result. Also, certain components or parts of the systems, devices, or apparatuses illustrated or described herein are omitted for the sake of brevity and clarity.

[0212] Accordingly, other embodiments are within the scope of the following claims, and the specification and / or drawings may be regarded in an illustrative rather than a restrictive sense.

[0213] Each of the individual variations or embodiments described and illustrated herein has individual components and elements that can be easily separated or combined with the elements of any other variation or embodiment. Multiple changes can be made to adapt a particular situation, material, composition of matter, process, one or more acts of a process, or one or more steps to the purpose, spirit, or scope of the invention.

[0214] The methods described herein can perform the described events in any logically possible order, as well as in the order described. Additionally, additional steps or operations can be provided or steps or operations can be deleted to obtain the desired result.

[0215] Furthermore, when a range of values is defined, all values intervening between the upper and lower limits of that range, as well as any other defined values or all intervening values within that defined range, shall be included within the scope of the present invention. Also, any element of an aspect of the present invention can be defined and claimed independently or in combination with any one or more of the elements described herein. For example, a description of a range from 1 to 5 should be considered to disclose sub-ranges such as from 1 to 3, from 1 to 4, from 2 to 4, from 2 to 5, from 3 to 5, etc., individual numerical values within that range, such as 1.5, 2.5, etc., and all or part of the increments therebetween.

[0216] All existing subject matter (e.g., publications, patents, patent applications) referred to herein shall be incorporated herein in its entirety, except where such subject matter may be inconsistent with the subject matter of the present invention (in which case, what is present herein shall prevail). The items referred to are provided only for the purpose of disclosure prior to the filing date of the present application. Nothing in this specification shall be construed as an admission that the present invention has no right to antedate such material by virtue of prior invention.

[0217] References to singular items include the possibility that there may be a plurality of the same item. More specifically, as used in this specification and the appended claims, the singular forms "a", "an", "said", and "the" include plural references unless the context clearly dictates otherwise. Further, it should be noted that the claims can be drafted to exclude any element. Thus, this description is intended to serve as a basis for using exclusive terms such as "solely" or "only" in connection with the recitation of claim elements or for using "negative" limitations. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the present invention pertains.

[0218] In understanding the scope of the present disclosure, the term "comprising" and its derivatives as used herein are intended to be open-ended terms that identify the presence of the recited features, elements, components, groups, integers, and / or steps, but do not preclude the presence of other unrecited features, elements, components, groups, integers, and / or steps. The same is true for terms having similar meanings such as "include", "have", and their derivatives. Also, the terms "part", "section", "portion", "member", "element", "component" used in the singular can have the meaning of either one part or a plurality of parts. As used herein, the directional terms "front, rear, upper, lower, vertical, horizontal, downward, transverse, and longitudinal", and any other similar directional terms, mean those positions of the device or apparatus, or those directions of the device or apparatus in which it is translated or moved. Finally, terms indicating degrees such as "substantially", "about", "approximately" used herein mean a reasonable deviation value from the specified value such that the final result does not change appreciably or substantially (e.g., a deviation of plus or minus 0.1%, plus or minus 1%, plus or minus 5% or plus or minus 10% as appropriate for such variations).

[0219] The present disclosure is not intended to be limited to the specific forms defined, but is intended to cover alternatives, modifications, and equivalents of the variations or embodiments described herein. Further, the scope of the present disclosure fully encompasses other variations or embodiments that may be apparent to those skilled in the art in view of the present disclosure.

Claims

1. A sample container including a sample chamber, the sample chamber consisting of a chamber side wall surrounding a chamber cavity configured to receive a sample, the sample container, and A reference sensor including a reference electrode material and a core, the core being in fluid communication with the sample chamber such that at least a portion of the sample is drawn by the core in the direction of the reference electrode material, the reference sensor, and An active sensor formed from a conductive substrate partially covered by an active electrode layer, the active sensor being coupled to at least a portion of the chamber side wall at a window opening formed along the chamber side wall, and no portion of the active sensor extending into the chamber cavity, the active sensor, and Comprising The active electrode layer faces the chamber cavity such that the sample in the chamber cavity can be in fluid contact with the active electrode layer through at least a portion of the chamber side wall surrounding the window opening. A sensor device for measuring a solution property of a sample, wherein the solution property of the sample is determined based on a potential difference measured between the active sensor and the reference sensor when the reference sensor and the active sensor are electrically coupled to a reader.

2. The sensor device according to claim 1, wherein the solution property to be measured is a redox potential and the active electrode layer is a platinum layer.

3. The sensor device according to claim 1, wherein the solution property to be measured is pH and the active electrode layer consists of a platinum oxide layer and a tantalum oxide layer.

4. The sensor device according to claim 1, wherein the conductive substrate is stainless steel.

5. The sensor device according to claim 1, wherein the active electrode layer has a thickness of the active electrode layer of about 50 nm to 500 nm.

6. The sensor device according to claim 5, wherein the active sensor further comprises an adhesive layer between the conductive substrate and the active electrode layer, and the adhesive layer has a thickness of the adhesive layer of 5 nm to 50 nm.

7. The sensor device according to claim 6, wherein a ratio of the thickness of the adhesive layer to the thickness of the active electrode layer is about 1:10 to 1:

20.

8. The sensor device according to claim 6, wherein the adhesive layer is a chromium layer.

9. The sensor device according to claim 1, wherein the active electrode layer has a thickness of the active electrode layer of at least 50 nm.

10. The sensor device according to claim 1, wherein the active sensor is insert-molded on the chamber sidewall while the sample container is formed by injection molding.

11. The sensor device according to claim 1, wherein the active sensor is press-molded on the chamber sidewall after the sample container is formed by injection molding.

12. The chamber sidewall comprises a recess that surrounds the window opening and is formed along the outer side surface of the chamber sidewall, and the active sensor is adhered to at least a part of the chamber sidewall within the recess via an adhesive. The sensor device according to claim 1.

13. The active sensor includes an active electrode side surface, a conductive substrate side surface opposite to the active electrode side surface, and a plurality of side surfaces, and the side surfaces are covered by at least one of the chamber sidewall and the adhesive to prevent the side surfaces from contacting the sample. The sensor device according to claim 1.

14. The sample chamber of the sensor device according to claim 1 is formed of at least one of polyoxymethylene, polyamide, polyethylene, acrylonitrile-butadiene-styrene, polycarbonate, and polypropylene.

15. The reference electrode material is a cured or solidified silver-silver chloride ink deposited or otherwise applied to the proximal end of the core of the core. The sensor device according to claim 1.

16. A sample container including a sample chamber, the sample container comprising a chamber sidewall surrounding a chamber cavity configured to receive a sample, A reference sensor including a reference electrode material and a core, the core being in fluid communication with the sample chamber such that at least a part of the sample is drawn in the direction of the reference electrode material by the core. An active sensor formed on a non-conductive printed circuit (PCB) substrate partially covered by an active electrode layer, wherein the active electrode layer is electrically coupled to a plurality of conductive contacts of the PCB substrate by conductive vias extending through the PCB substrate, the active sensor is coupled to at least a part of the chamber sidewall at a window opening formed along the chamber sidewall, no part of the active sensor extends into the chamber cavity, and the sample in the chamber cavity can be in fluid contact with the active electrode layer through at least a part of the chamber sidewall surrounding the window opening, and the active electrode layer faces the chamber cavity, an active sensor, comprising, A sensor device for measuring the solution properties of a sample, wherein the solution properties of the sample are determined based on the potential difference measured between the active sensor and the reference sensor when the reference sensor and the active sensor are electrically coupled to a reader. [

17. ] A sample container including a sample chamber, wherein the sample chamber consists of a chamber sidewall surrounding a chamber cavity configured to receive a sample, a sample container, A reference sensor including a reference electrode material and a core element, wherein the core element is in fluid communication with the sample chamber such that at least a part of the sample is drawn in the direction of the reference electrode material by the core element, a reference sensor, An active sensor formed from a non-conductive polymer substrate including through holes, wherein one surface of the polymer substrate and one end of the through holes are covered by an active electrode layer, the other surface of the polymer substrate and the other end of the through holes are covered by a conductive layer, and the active electrode layer is electrically coupled to the conductive layer through a conductive coating covering a plurality of side surfaces of the through holes, an active sensor, comprising, the active sensor is coupled to at least a part of the chamber sidewall at a window opening formed along the chamber sidewall, no part of the active sensor extends into the chamber cavity, and the active electrode layer faces the chamber cavity such that the sample in the chamber cavity can be in fluid contact with the active electrode layer through at least a part of the chamber sidewall surrounding the window opening, A sensor device for measuring the solution characteristics of a sample, wherein the solution characteristics of the sample are determined based on the potential difference measured between the active sensor and the reference sensor when the reference sensor and the active sensor are electrically coupled to a reader.

18. A sample container including a sample chamber, the sample chamber comprising chamber side walls surrounding a chamber cavity configured to receive a sample, the sample container, A reference sensor including a reference electrode material and a core element, the core element being in fluid communication with the sample chamber such that at least a portion of the sample is drawn by the core element in the direction of the reference electrode material, the reference sensor, An active sensor formed from a conductive stud partially covered by an active electrode layer, the active sensor being coupled to at least a portion of the chamber side wall at a window opening formed along the chamber side wall, a portion of the conductive stud covered by the active electrode layer extending into the chamber cavity such that the sample in the chamber cavity can be in fluid contact with the active electrode layer, and an end portion of the conductive stud that does not extend into the chamber cavity extending out of the chamber side wall, the active sensor, Comprising, A sensor device for measuring the solution characteristics of a sample, wherein the solution characteristics of the sample are determined based on the potential difference measured between the active sensor and the reference sensor when the reference sensor and the active sensor are electrically coupled to a reader.

19. The step of cleaning the conductive substrate by acid and base treatment, The step of depositing an adhesive layer on one side of the conductive substrate, The step of depositing an active electrode layer on the adhesive layer, The step of singulating the conductive substrate covered by the adhesive layer and the active electrode layer to obtain an active sensor sized to cover a window opening formed along the chamber side wall of the sample chamber, The step of coupling the active sensor to at least a portion of the chamber side wall, comprising, whereby no part of the active sensor extends into the chamber cavity within the sample chamber, and any sample within the chamber cavity can be in fluid contact with the active electrode layer through at least a part of the chamber sidewall surrounding the window opening, a method of manufacturing a sensor device for measuring solution characteristics of a sample, wherein the active electrode layer faces the chamber cavity.

20. providing a non-conductive printed circuit (PCB) substrate; depositing an active electrode layer on one side of the PCB substrate, wherein the active electrode layer is electrically coupled to a plurality of conductive contacts of the PCB substrate by conductive vias extending through the PCB substrate after the deposition step; fragmenting the PCB substrate covered by the active electrode layer to obtain an active sensor sized to cover a window opening formed along a chamber sidewall of a sample chamber, wherein the active sensor includes at least one conductive via extending through the PCB substrate; coupling the active sensor to at least a part of the chamber sidewall; comprising, whereby no part of the active sensor extends into the chamber cavity within the sample chamber, and any sample within the chamber cavity can be in fluid contact with the active electrode layer through at least a part of the chamber sidewall surrounding the window opening, a method of manufacturing a sensor device for measuring solution characteristics of a sample, wherein the active electrode layer faces the chamber cavity.

21. providing a non-conductive polymer substrate having a plurality of through-holes; depositing a conductive layer on one side of the polymer substrate; depositing an active electrode layer on another side of the polymer substrate, wherein one end of the through-hole is covered by the active electrode layer, the other end of the through-hole is covered by the conductive layer, and the active electrode layer is electrically coupled to the conductive layer through a conductive coating covering a plurality of lateral sides of the through-hole after the deposition step; To obtain an active sensor sized to cover a window opening formed along the chamber sidewall of the sample chamber, a step of fragmenting the polymer substrate covered with the active electrode layer and the conductive layer, wherein the active sensor includes at least one through hole covered with the active electrode layer and the conductive layer, the fragmenting step; A step of bonding the active sensor to at least a part of the chamber sidewall, whereby no part of the active sensor extends into the chamber cavity within the sample chamber, and any sample within the chamber cavity can be in fluid contact with the active electrode layer through at least a part of the chamber sidewall surrounding the window opening, and the active electrode layer faces the chamber cavity, a method for manufacturing a sensor device for measuring solution characteristics of a sample.

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