Patent Application
20180328841
All publications and patent applications mentioned in this specification are incorporated herein by reference in their entirety to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference.
Embodiments described relate generally to quantitative colorimetric capnometry methods and systems.
Methods and devices for measuring quantitative airway carbon dioxide (CO2) gas exchange concentrations and respiratory rate of a subject's breath (capnometry) are well known in the clinical markets. In fact, the use of capnometry during intubated surgical and otherwise critical ventilated patient situations is mandated by standards organizations because it is critical in maintaining safety. By far the most common technology used in commercial instruments is IR spectroscopy because of its accuracy, precision, speed of response and reliability. Infrared absorption spectroscopy capnometers quantify the subject's airway CO2 gas exchange in real time without any airway perturbation or violation of sterility. Unfortunately, IR-based capnometry are technically complex and expensive compared to other common medical parameter measurements such as temperature, blood pressure, ECG, heart rate and pulse oximetry. Now that the use of capnometry has expanded outside the in-hospital environment to pre-hospital emergency care including non-intubated subject monitoring applications such as dentistry, pain management, conscious sedation, in-home use, etc., there is an increased awareness of the need for less expensive capnometry instruments. There is also a need for a low cost way of measuring a user's breathing rate and end-tidal CO2 levels as part of a breathing therapy, such as those described in WO 2015/009792.
There are many other techniques for measuring gas exchange in a subject's breath. Among these include mass spectrometry, Raman scattering, photoacoustic, piezoelectric, paramagnetic and chemical based instruments. All of these techniques have specific tradeoffs with respect to their complexity, performance and cost. In examining the aspects of these tradeoffs, one technique stands alone as having potential for simplicity, meeting adequate performance criteria at considerably lower cost than other methods; the chemical based colorimetric technique.
Chemical based colorimetric techniques have been utilized in many other applications including qualitative human breath CO2 detection. However, one of the challenges in using colorimetric techniques is its ability to achieve sufficient response time to capture rapidly changing CO2 concentrations such as is found in a subject's ventilation pattern. Commercially available airway colorimetric products first appeared in the late 1980's, but could only give relative qualitative indications of CO2 concentrations due to their slow response. In the 1990's, improvements to the indicator chemistry formulations were made to enhance the speed of response to breath-by-breath gas concentration variations. For example, in 1994 Dr. Andras Gedeon published test results of the response time of a qualitative colorimetric indicator compared with the response time of a quantitative IR spectroscopy-based capnometer showing significant similar breath-by-breath response times. Details regarding these test results are described in the paper “A New Colorimetric Breath Indicator (Colibri)” published in Anesthesia (1994) volume 49, pages 798-803, which is herein incorporated by reference in its entirety. Since then, Dr. Gedeon and others have continued to develop and manufacture qualitative colorimetric indicators primarily for use with intubation verification.
WO 2015/009792 discloses quantitative colorimetric indicators that interrogate the color change of a chemical colorimetric indicator to quantify carbon dioxide concentrations. The use of some chemical colorimetric indicators can present additional challenges, such as batch to batch differences in the chemical colorimetric indicator and changes to the colorimetric indicator after manufacture and prior to use. The colorimetric indicator can be sensitive to environmental factors. Contaminants and age can decrease the responsiveness and in turn accuracy of the quantitative colorimetric indicator. The colorimetric indicator can be replaced periodically or when the performance quality is decreased. Improved methods and apparatuses are provided herein for replacing the colorimetric indicator in the quantitative colorimetric indicator. Each colorimetric indicator may have slightly different responsiveness to carbon dioxide. Each colorimetric indicator can be characterized prior to packaging and use. Calibration of the colorimetric indicator after removal from the packaging and prior to use can present challenges to the user. Improved methods and apparatuses for calibrating colorimetric indicators are desired and disclosed herein. These characterization and calibration techniques can improve reliability, accuracy and ease of use of the quantitative colorimetric indicator.
The present disclosure relates to quantitative colorimetric systems and methods for using the same. The methods can include characterization and calibration methods for the colorimetric indicator. The quantitative colorimetric systems can be used to provide a user with a breathing therapy. Cartridges are also disclosed including a chemical colorimetric indicator along with a gas container having a reference gas.
In general, in one embodiment, a method of calibrating a quantitative colorimetric measurement system including humidifying a chemical colorimetric indicator; exposing the chemical colorimetric indicator to a first gas; measuring a first color of the chemical colorimetric indicator based on the exposure to the first gas; exposing the chemical colorimetric indicator to a second gas having a different CO2 concentration than the first gas; measuring a second color of the chemical colorimetric indicator based on the exposure to the second gas; and deriving a span CO2 calibration based on the difference between the first color of the chemical colorimetric indicator and the second color of the chemical colorimetric indicator.
This and other embodiments can include one or more of the following features. Humidifying the chemical colorimetric indicator can include contacting the chemical colorimetric indicator with air exhaled by a user of the quantitative colorimetric CO2 measurement system. The method can further include humidifying the chemical colorimetric indicator after measuring the first color of the chemical colorimetric indicator and prior to exposing the chemical colorimetric indicator to the second gas. Humidifying the chemical colorimetric indicator can include contacting the chemical colorimetric indicator with air exhaled by a user of the quantitative colorimetric measurement system. Humidifying the chemical colorimetric indicator can include contacting the chemical colorimetric indicator with a humidity source. The quantitative colorimetric measurement system can include a first removable cartridge which can include the chemical colorimetric indicator and a second removable cartridge including the humidity source, which can further include humidifying the chemical colorimetric indicator by passing ambient air through the humidity source into contact with the chemical colorimetric indicator. The first removable cartridge can further include a humidity-moisture exchanger (HME). Humidifying can include passing ambient air through the humidity source, HME, and the colorimetric indicator. Humidifying the chemical colorimetric indicator can include humidifying the chemical colorimetric indicator to a relative humidity of greater than about 60%. Humidifying the chemical colorimetric indicator can include humidifying the chemical colorimetric indicator to a relative humidity of greater than about 90%. The method can include humidifying the chemical colorimetric indicator; exposing the chemical colorimetric indicator to the first gas; measuring the first color of the chemical colorimetric indicator based on the exposure to the first gas; exposing the chemical colorimetric indicator to the second gas having a different CO2 concentration than the first gas; measuring the second color of the chemical colorimetric indicator based on the exposure to the second gas; and deriving the span CO2 calibration based on the difference between the first color of the chemical colorimetric indicator and the second color of the chemical colorimetric indicator can be performed in about 5 minutes or less. The method can further include applying the span calibration to a measurement of a color of the chemical colorimetric indicator exposed to a breath sample. Exposing the chemical colorimetric indicator to a second gas can include exposing the indicator to a sealed container filled with a reference sample having a known carbon dioxide concentration. The known carbon dioxide concentration can be from about 4% to about 7% carbon dioxide. The sealed container filled with the reference sample having the known carbon dioxide concentration can have a known humidity content. Exposing the indicator to the first gas can include exposing the chemical colorimetric indicator to a sealed container filled with a reference sample having a known carbon dioxide concentration. The sealed container filled with the reference sample having the known carbon dioxide concentration can have a known humidity content. Humidifying the chemical colorimetric indicator can include contacting the first gas with a humidification source. Exposing the indicator to the first gas can include exposing the chemical colorimetric indicator to ambient air. The method can further include engaging a first cartridge with the quantitative colorimetric measurement system, the first cartridge can contain the chemical colorimetric indicator. The method can further include engaging a second cartridge with the quantitative colorimetric measurement system, the second cartridge can contain the reference gas and a humidity source. A breathing therapy method can include calibrating a quantitative colorimetric measurement system using any of the above methods and can use the quantitative colorimetric measurement system for a breathing therapy for up to seven days. A breathing therapy method can include calibrating a quantitative colorimetric measurement system using any of the above methods and can use the quantitative colorimetric measurement system for a breathing therapy greater than 28 days. The method can further include removing the second cartridge containing the reference gas and the humidity source and engaging a fresh second cartridge containing a second reference gas and a second humidity source with the quantitative colorimetric measurement system. The method can further include using the quantitative colorimetric measurement system with the fresh second cartridge for a breathing therapy for up to seven days. The method can further include replacing the chemical colorimetric indicator with a second chemical colorimetric indicator after about 5-7 days. The method can further include humidifying the second chemical colorimetric indicator; exposing the second chemical colorimetric indicator to a first gas; measuring a first color of the second chemical colorimetric indicator based on the exposure to the first gas; exposing the second chemical colorimetric indicator to a second gas; measuring a second color of the second chemical colorimetric indicator based on the exposure to the second gas having a different CO2 concentration than the first gas; and deriving a span calibration based on the difference between the first color of the second chemical colorimetric indicator and the second color of the second chemical colorimetric indicator. Humidifying the second chemical colorimetric indicator can include contacting the second chemical colorimetric indicator with a humidity source. The method can further include humidifying the second chemical colorimetric indicator by passing ambient air through the humidity source into contact with the chemical colorimetric indicator. Humidifying the second chemical colorimetric indicator can include humidifying the second chemical colorimetric indicator to a relative humidity of greater than about 60%. The first gas can have a concentration of CO2 of about 0% to about 2%. The method can further include verifying the humidity of the chemical colorimetric indicator after humidifying the chemical colorimetric measurement system. Verifying the humidity of the chemical colorimetric indicator can include measuring a color of a humidity sensor. The method can further include determining if the color of the humidity sensor corresponds to a humidity above a threshold humidity level. The method can further include after verifying the humidity of the chemical colorimetric indicator, measuring the first color of the chemical colorimetric indicator based on the exposure to the first gas. The method can further include measuring a temperature of the chemical colorimetric indicator when measuring the first color of the chemical colorimetric indicator. The method can further include applying the temperature of the chemical colorimetric indicator to the measured first color of the chemical colorimetric indicator when measuring the first color of the chemical colorimetric indicator. The method can further include measuring a humidity of the chemical colorimetric indicator when measuring the first color of the chemical colorimetric indicator. The method can further include determining an adjusted measurement signal corresponding to the first color of the chemical colorimetric indicator and the measured humidity of the chemical colorimetric indicator. The method can further include receiving an exhaled breath sample from a user; contacting the chemical colorimetric indicator with the exhaled breath sample; measuring a temperature of the chemical colorimetric indicator; measuring a humidity of the chemical colorimetric indicator; measuring a color of the chemical colorimetric indicator based on the exposure to the exhaled breath sample; obtaining a voltage measurement corresponding to the color of the colorimetric indicator and the humidity of the chemical colorimetric indicator; and determining a quantitative value of the CO2 in the exhaled breath sample from the humidity of the chemical colorimetric indicator, the temperature of the chemical colorimetric indicator, and the voltage measurement. The method can further include comparing the span calibration to a factory characterization data for the chemical colorimetric indicator. The method can further include adjusting a calibration curve for the colorimetric indicator based on the comparison of the factory characterization data and the calibration data. The quantitative colorimetric measurement system can include a light source to determine the color of the chemical colorimetric indicator, and can further include adjusting properties of the light source to align the span calibration with the factory characterization data. Adjusting the properties of the light source can include modifying an electrical current supplied to the light source.
In general, in one embodiment, a method of providing a breathing therapy including receiving an exhaled breath sample from a user; contacting the chemical colorimetric indicator with the exhaled breath sample; measuring a temperature of the chemical colorimetric indicator; measuring a humidity of the chemical colorimetric indicator; measuring a color of the chemical colorimetric indicator based on the exposure to the exhaled breath sample; obtaining a voltage measurement corresponding to the color of the colorimetric indicator and the humidity of the chemical colorimetric indicator; and determining a quantitative value of the CO2 in the exhaled breath sample from the humidity of the chemical colorimetric indicator, the temperature of the chemical colorimetric indicator, and the voltage measurement.
This and other embodiments can include one or more of the following features. The method can further include outputting a set of visual and/or audio cues from the quantitative colorimetric system with instructions for the user to adjust their breathing pattern to coincide with the cues to thereby modify the user's exhaled CO2 levels. The method can further include providing the set of visual cues including a visual indication of a respiration rate relative to a target respiration rate. The visual indication of the respiration rate can include a circular pattern with an increasing and decreasing diameter corresponding to the user's exhaled CO2 level. The visual indication of the target respiration rate can include a circular target pattern. The method can further include changing a diameter of the circular target pattern of the target respiration rate based on a difference between the user's exhaled CO2 levels and a target user's exhaled CO2 levels. The method can further include changing a location of a target line to vary a distance between the target line and a reference point based on a difference between the user's exhaled CO2 levels and a target user's exhaled CO2 levels. The breathing pattern can include the exhaled CO2 level and respiration rate. The method can further include displaying the user's measured CO2 levels to provide visual feedback during treatment. The method can further include the therapy directing the user's end-tidal CO2 levels to a level between about 37 mmHg and 43 mmHg. The method can further include treating post-traumatic stress disorder (PTSD), panic disorder, anxiety, asthma, hypertension, obsessive-compulsive disorder, social phobia, depression, apnea, migraines, or epilepsy by training the user to modify their exhaled CO2 levels.
In general, in one embodiment, an apparatus including a cartridge including a chemical colorimetric indicator and a humidity moisture exchanger, the cartridge configured to removably engage with a quantitative colorimetric measurement system.
This and other embodiments can include one or more of the following features. The apparatus can further include a sealed container including a reference gas including a known concentration of carbon dioxide. The known carbon dioxide concentration can be from about 4% to about 7% carbon dioxide. The sealed container can be configured for a single use. The sealed container can be configured to be resealable. The sealed container can be integral with the cartridge. The sealed container can be separate from the cartridge. The sealed container can contain a known humidity content. The apparatus can further include a second sealed container having a second known concentration of carbon dioxide. The second known concentration of carbon dioxide can be less than about 2% carbon dioxide. The second sealed container can contain a known humidity content. The apparatus can further include a humidification module configured to humidify an incoming gas prior to the gas contacting the chemical colorimetric indicator. The humidification module can include a humidity reservoir. The humidification module can include a wet filter. The humidification module can include a water reservoir. The sealed container can be contained in a second removable cartridge configured to removably engage with a quantitative colorimetric measurement system. The apparatus can further include a humidity source in the second removable cartridge. The cartridge can further include a humidity sensor. The apparatus can further include the quantitative colorimetric measurement system. The quantitative colorimetric measurement system can further include a humidity sensor. The quantitative colorimetric measurement system can include an electro-optical sensor assembly including one or more light sources and a light detection material configured to detect light reflected off of the chemical colorimetric indicator by the light source. The electro-optical sensor assembly can further be configured to generate an electrical signal based on the light detected by the light detection material. The apparatus can further include a processor in communication with the electro-optical sensor assembly. The processor can be configured to receive the electrical signals generated by the electro-optical sensor assembly. The processor can utilize the signals to compute the quantity of carbon dioxide exposed to the chemical colorimetric indicator. The chemical colorimetric indicator can be adapted to change color in response to exposure to a quantity of carbon dioxide gas. The electro-optical assembly can be configured to detect light reflected off of the humidity sensor. The humidity sensor can be adapted to change color in response to exposure to humidity. The humidity sensor can be downstream of the chemical colorimetric indicator.
In general, in one embodiment, a quantitative colorimetric measurement system including an electro-optical sensor assembly including one or more light sources and a light detection material configured to detect light reflected off of a chemical colorimetric indicator by the light source, the electro-optical sensor assembly configured to generate an electrical signal based on the light detected by the light detection material; a humidity sensor adapted to measure a humidity of the chemical colorimetric indicator; a temperature sensor adapted to measure a temperature of the chemical colorimetric indicator; a processor configured to determine a quantitative value of CO2 detected by the chemical colorimetric indicator from the humidity of the chemical colorimetric indicator, the temperature of the chemical colorimetric indicator, and a voltage measurement corresponding to the electrical signal based on the light detected by the light detection material; and a removable cartridge including the chemical colorimetric indicator and a humidity moisture exchanger, the cartridge configured to removably engage with the quantitative colorimetric measurement system.
This and other embodiments can include one or more of the following features. The system can further include a second removable cartridge including a humidity source and a reference gas having a known concentration of carbon dioxide, the second cartridge can be configured to removably engage with the quantitative colorimetric measurement system. In general, in one embodiment, a breathing therapy method including receiving at least a portion of a user's exhaled air in a gas inlet of a quantitative colorimetric measurement system; measuring the humidity of a humidity sensor within the quantitative colorimetric measurement system that is exposed to the user's exhaled air; confirming that the humidity of the humidity sensor is above a threshold humidity; and measuring a user's end-tidal CO2 levels with the quantitative colorimetric measurement system based on a color change resulting from exposure of the system to the user's exhaled air.
This and other embodiments can include one or more of the following features. The method can further include outputting a set of visual and/or audio cues from the quantitative colorimetric system with instructions for the user to adjust their breathing pattern to coincide with the cues to thereby modify the user's exhaled CO2 levels. The breathing pattern can include the exhaled CO2 level and respiration rate. The method can further include displaying the user's measured CO2 levels to provide visual feedback during treatment. The method can further include displaying the user's breathing rate to provide visual feedback during treatment. The method can further include the therapy directing the user's end-tidal CO2 levels to a level between about 37 mmHg and 43 mmHg. The method can further include treating post-traumatic stress disorder (PTSD), panic disorder, anxiety, asthma, hypertension, obsessive-compulsive disorder, social phobia, depression, apnea, migraines, or epilepsy by training the user to modify their exhaled CO2 levels. The method can further include measuring a temperature of a chemical colorimetric indicator of the quantitative colorimetric measurement system when measuring the user's end-tidal CO2 levels. The method can further include applying a temperature correction to measured user's end-tidal CO2 levels based on the temperature of the chemical colorimetric indicator when measuring the user's end-tidal CO2 levels.
In general, in one embodiment, a method for characterizing a chemical colorimetric indicator including contacting the chemical colorimetric indicator sequentially with a plurality of gases having a plurality of different concentrations of carbon dioxide; measuring a color of the chemical colorimetric indicator based on an exposure to each of the plurality of gases by reflecting a first light source having a first wavelength off of the chemical colorimetric indicator and detecting a first light reflected from the colorimetric indicator to generate a plurality of measurement signals; determining a characterization for the chemical colorimetric indicator by analyzing the plurality of measurement signals corresponding to the plurality of different concentrations of carbon dioxide; and calculating a calibration curve for the chemical colorimetric indicator based on the characterization for the chemical colorimetric indicator.
This and other embodiments can include one or more of the following features. The calibration curve can be a polynomial equation that can be a function of the measurement signal. The calibration curve can be a polynomial equation that can be a function of the measurement signal and a temperature of the chemical colorimetric indicator. The polynomial equation can include: CO2(V)=[A′*V3]+[B′*V2]+[C′*V]+D′. The polynomial equation can include: CO2(V,T)=[A′(T)*V3]+[B′(T)*V2]+[C′(T)*V]+D′(T) with
A′(T)=a1*T2+b1*T+c1
B′(T)=a2*T2+b2*T+c2
C′(T)=a3*T2+b3*T+c3
D′(T)=a4*T2+b4*T+c4.
Calculating the calibration curve can include calculating a plurality of coefficients for the calibration curve. The plurality of CO2 concentrations can be from about 0% to about 8%. The method can further include measuring the color of the chemical colorimetric indicator by reflecting a plurality of light sources having a plurality of wavelengths off of the chemical colorimetric indicator and detecting a plurality of reflected light to generate a plurality of measurement signals. The method can further include measuring the color of the chemical colorimetric indicator at a plurality of different temperatures. The plurality of temperatures can be between about 15° C. and 31° C. The method can further include deriving coefficients for the temperature sensitive functions of the calibration curve. The method can further include measuring the color of the chemical colorimetric indicator at a plurality of different humidity levels. The method can further include deriving coefficients for a humidity sensitive function for the measurement signal of the chemical colorimetric indicator. The coefficients for the humidity sensitive function can include p, q, and r from the following equation with RH referring to a relative humidity:
The method can further include recording the calibration curve for the chemical colorimetric indicator. The method can further include packaging the chemical colorimetric indicator. The method can further include encoding the calibration curve with packaging.
In general, in one embodiment, a method of calibrating a chemical colorimetric indicator including exposing the chemical colorimetric indicator to a first gas having a first concentration of carbon dioxide; measuring a color of the chemical colorimetric indicator based on the exposure to the first gas by reflecting a first light source having a first wavelength off of the chemical colorimetric indicator and detecting a first light reflected from the colorimetric indicator to generate a first measurement signal; exposing the chemical colorimetric indicator to a second gas having a second concentration of carbon dioxide; measuring the color of the chemical colorimetric indicator based on the exposure to the second gas by reflecting the first light source having the first wavelength off of the chemical colorimetric indicator and detecting the second light reflected from the colorimetric indicator to generate a second measurement signal; determining a span CO2 calibration based on the difference between the first measurement signal and the second measurement signals; and comparing the span calibration to a factory characterization data for the chemical colorimetric indicator.
This and other embodiments can include one or more of the following features. The method can further include adjusting a calibration curve for the colorimetric indicator based on the comparison of the factory characterization data and the calibration data. The method can further include adjusting the first light source properties to align the span calibration with the factory characterization data. The method can further include optimizing the first light source properties to align the span calibration with the factory characterization data. Optimizing can include adjusting the first light source properties to match the first measurement signal and second measurement signal to the characterization data. The method can further include removing the chemical colorimetric indicator from a package containing the colorimetric indicator. The package can include the factory characterization data for the chemical colorimetric indicator. The method can further include engaging the chemical colorimetric indicator with a quantitative colorimetric measurement system. The method can further include providing the factory characterization data for the chemical colorimetric indicator to the quantitative colorimetric measurement system. The method can further include humidifying a chemical colorimetric indicator prior to exposing the chemical colorimetric indicator to the first gas. The method can further include monitoring a user's breathing using the quantitative colorimetric measurement system. The first measurement signal and plurality of second measurement signals can include a voltage measurement detected by one or more photodiodes from the light reflected from the chemical colorimetric indicator.
In general, in one embodiment, a kit including a chemical colorimetric indicator configured to be used with a quantitative carbon dioxide measurement system; and characterization data for the chemical colorimetric indicator.
This and other embodiments can include one or more of the following features. The characterization data can include coefficients for a calibration curve. The calibration curve can be a polynomial equation and the coefficients correspond to the polynomial equation. The coefficients can include coefficients for a temperature sensitive equation. The calibration curve can be a function of a voltage measured by the quantitative carbon dioxide measurement system. The kit can further include a sealed packaging material containing the chemical colorimetric indicator. The packaging material can be moisture resistant and light resistant. The characterization data can be encoded on a packaging of the chemical colorimetric indicator in a machine readable format. The polynomial equation can include:
CO2(V)=[A′*V3]+[B′*V2]+[C′*V]+D′.
The polynomial equation can include:
CO2(V,T)=[A′(T)*V3]+[B′(T)*V2]+[C′(T)*V]+D′(T) with
A′(T)=a1*T2+b1*T+c1
B′(T)=a2*T2+b2*T+c2
C′(T)=a3*T2+b3*T+c3
D′(T)=a4*T2+b4*T+c4.
The coefficients can include coefficients for a humidity sensitive equation. The coefficients for the humidity sensitive equation can include p, q, and r from the following equation with RH referring to a relative humidity:
The chemical colorimetric indicator can be part of a removable cartridge configured to removably engage with the quantitative carbon dioxide measurement system. The kit can further include a humidity moisture exchanger.
In general, in one embodiment, a method of calibrating a quantitative colorimetric measurement system including instructing a user of the quantitative colorimetric measurement system to provide a breath sample to a chemical colorimetric indicator to humidify the chemical colorimetric indicator; verifying that the chemical colorimetric indicator has been humidified; instructing the user to expose the chemical colorimetric indicator to a first ambient gas; measuring a first color of the chemical colorimetric indicator based on the exposure to the first gas; instructing the user to expose the chemical colorimetric indicator to a reference gas; measuring a second color of the chemical colorimetric indicator based on the exposure to the reference gas; and deriving a span calibration based on the difference between the first color of the chemical colorimetric indicator and the second color of the chemical colorimetric indicator.
This and other embodiments can include one or more of the following features. The first gas can have a concentration of CO2 of about 0% to about 2%. The reference gas can have a known carbon dioxide concentration of from about 4% to about 7% carbon dioxide. Verifying the humidity of the chemical colorimetric indicator can include measuring a color of a humidity sensor. The method can further include determining if the color of the humidity sensor corresponds to a humidity above a threshold humidity level. The method can further include after verifying the humidity of the chemical colorimetric indicator, instructing the user to expose the chemical colorimetric indicator to a first ambient gas. The method can further include measuring a temperature of the chemical colorimetric indicator when measuring the first color of the chemical colorimetric indicator. The method can further include applying the temperature of the chemical colorimetric indicator to the measured first color of the chemical colorimetric indicator when measuring the first color of the chemical colorimetric indicator. The chemical colorimetric indicator can be adapted to change color in response to exposure to a quantity of carbon dioxide gas. The method can further include comparing the span CO2 calibration to a characterization data provided with the chemical colorimetric indicator. The method can further include adjusting a calibration of the chemical colorimetric indicator based on the comparison of the span CO2 to the characterization data provided with the chemical colorimetric indicator. The method can further include adjusting one or more optical properties of the quantitative colorimetric measurement system to correlate the span CO2 calibration to the characterization data. Adjusting one or more optical properties can include adjusting one or more light emitting diodes (LEDs) of the quantitative colorimetric measurement system.
The novel features of the invention are set forth with particularity in the claims that follow. A better understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are utilized, and the accompanying drawings of which:
Apparatuses, methods, and kits are disclosed herein for use in quantitative colorimetric measurement systems. The methods can include improved methods for characterizing and calibrating a chemical colorimetric indicator used in the quantitative colorimetric measurement system.
The chemical colorimetric indicator can be characterized in a laboratory setting prior to packaging. However, the chemical colorimetric indicator can change after packaging and through exposure to environmental elements. Consequently, it is desirable to further calibrate the chemical colorimetric indicator prior to or at the time of use to improve the accuracy and reliability of the quantitative colorimetric indicator.
Calibrating the chemical colorimetric indicator outside of the laboratory, such as at home, can be challenging. Typically, laboratories have a clean environment, access to reference gases, and a technician that has experience with performing the calibration. A home environment usually does not have all of these conditions. It is desirable to provide an easy and reliable calibration process that can be used by a patient or subject at home prior to receiving a breathing therapy. It is also desirable for the calibration to be automatic or to require few user steps or intervention. In some embodiments the calibration of the chemical colorimetric indicator can happen without user intervention or input. The calibration of the chemical colorimetric indicator can also take about 5 minutes or less.
The calibration steps can include sampling room air/ambient air to approximate a reference gas having a carbon dioxide concentration close to zero along with sampling a reference gas having a known carbon dioxide concentration. The carbon dioxide content of the room air can be estimated. For example, a carbon dioxide content of 0% to about 0.10% can be assumed for the room air. In some embodiments the carbon dioxide content of the room air is assumed to be about 0.07%. The reference gas can be provided with the chemical colorimetric indicator. The reference gas can have a known concentration around the desired upper range for analysis, such as a concentration between about 4% to 6% carbon dioxide. The quantitative colorimetric indicator can reflect light off of the colorimetric indicator and measure the reflected light to produce a measurement signal. The measurement signals can be converted to a corresponding carbon dioxide level using the characterization and calibration data for the specific chemical colorimetric indicator.
Another challenge with properly characterizing and calibrating a chemical colorimetric indicator is that the chemical colorimetric indicator or film typically requires a threshold level of humidification in order to accurately and properly respond to the concentration of the carbon dioxide. The film can be humidified controllably in a laboratory setting with the proper materials and procedures; however, this can be challenging in an environment outside of the laboratory during calibration prior to use. One humidification source for calibration prior to use is the exhaled breath of the patient or subject using the quantitative colorimetric indicator. The chemical colorimetric indicator can be humidified prior to calibration by prompting the user/subject to exhale into the device or by sampling the exhaled breath. The chemical colorimetric indicator can then be calibrated using the room air and a reference gas after humidification of the chemical colorimetric indicator.
The humidification can result in surface adsorption of water on the surface of the chemical colorimetric indicator. Once the adsorption of water has exceeded a threshold amount the chemical colorimetric indicator can be used. The adsorption of water on the surface of the chemical colorimetric indicator is different than directly contacting the chemical colorimetric indicator with liquid phase water. Liquid saturation or liquid contacting the chemical colorimetric indicator can adversely change the properties of the chemical colorimetric indicator and change the chemical colorimetric indicator's response to carbon dioxide. Fully saturating the chemical colorimetric indicator with water can prevent the chemical colorimetric indicator from working or predictably responding to gas phase carbon dioxide.
In some embodiments the humidification threshold level is between about 10% and 100% humidification. In some embodiments the humidification threshold level is between about 40% and 100% humidification. In some embodiments the humidification threshold level is between about 60% and 100% humidification. In some embodiments the humidification threshold level is greater than about 40% humidification. In some embodiments the humidification threshold level is greater than about 60% humidification.
The measurement signal produced by the interrogation of the chemical colorimetric indicator can also vary with the humidity of the indicator. The humidity of the chemical colorimetric indicator or the environment adjacent to or surrounding the chemical colorimetric indicator can be measured with a humidity sensor or probe. A humidity compensation or correction can then be applied to the measurement signal corresponding to the color of the chemical colorimetric indicator.
The chemical colorimetric indicator can be humidified in other ways in some embodiments. For example, humidification of the colorimetric material can be done by a humidifier component, humidification module, humidity source, etc. In some embodiments the user can put water into the humidifier component. In some embodiments the humidifier component can be prepackaged with a moisture level. The user can then open the humidifier component and place the humidifier in the system prior to calibration. In some embodiments the humidity source can be provided in a removable cartridge. Ambient or room air can be pulled into the device and humidified with the humidity source from the removable cartridge. The humidified air can be used to humidify components of the systems, such as the chemical colorimetric indicator. The humidifier component can also be included as part of a cartridge also containing the calibration gas.
Step by step instructions can be provided to the subject using the quantitative colorimetric indicator to perform the calibration steps described herein.
In some embodiments the humidification of the chemical colorimetric indicator can be verified by interrogating a humidity sensor with the light source and measuring the reflected light. After verifying the humidification of the chemical colorimetric indicator the subject can perform a breathing therapy with the quantitative colorimetric indicator. Methods for providing a breathing therapy are disclosed in WO 2015/009792, which is incorporated by reference in its entirety. Any of the breathing therapy methods disclosed in WO 2015/009792 can be used with the devices and methods disclosed herein.
The apparatuses can include cartridges with the chemical colorimetric indicator that can be used with the quantitative colorimetric measurement system. The cartridges can removably engage with the housing of the quantitative colorimetric measurement system. After the user is done with the chemical colorimetric indicator the chemical colorimetric indicator needs to be replaced the cartridge can be removed and a fresh cartridge can be inserted into the quantitative colorimetric measurement system. The cartridge/chemical colorimetric indicator can be provided with a reference gas having a known concentration of carbon dioxide. The reference gas can be provided in a container integral with the cartridge or separate from the cartridge. The chemical colorimetric indicator can be calibrated after engaging the cartridge with the quantitative colorimetric measurement system.
The cartridges can also include characterization data determined during the characterization of the chemical colorimetric indicator at the laboratory prior to packaging. The quantitative colorimetric measurement system can read (e.g., via RFID, barcode, memory chip internal to the cartridge, etc.) the encoded calibration data for the chemical colorimetric indicator prior to or when the cartridge is engaged with the rest of the system. The encoded laboratory characterization data can be compared to the calibration data/curve determined during the calibration done by the user and adjustments made if necessary.
More specific examples of the methods and apparatuses disclosed herein are discussed below with reference to the Figures and examples. Figures describe aspects of quantitative colorimetric carbon dioxide measuring systems that can be used with the method and apparatuses disclosed herein.
A pump 310 can be included within the housing 301 to pump the incoming gas sample. In some embodiments the pump 310 can be located downstream of the colorimetric indicator to effectively pull the incoming gas sample passed the porous colorimetric indicator. In some embodiments the pump can be upstream of the colorimetric indicator to pump the gas sample passed the colorimetric indicator. The system 300 includes operating electronics 312. The operating electronics can control the system to perform various processing steps as described herein. In some embodiments the operating electronics receive the measurement signal from the electro-optical assembly and calculate properties associated with the measurement signal. In some embodiments the operating electronics receive the measurement signal and send the measurement signal to a processor external to the system 300, with the external processor performing the calculations and analysis of the measurement signal. In some embodiments the system 300 includes a wireless transmitter 314 to transmit data to an external processor, such as a processor on a computer, tablet computer, or smartphone. The wireless transmitter can transmit data via Bluetooth or other wireless data transfer protocol. The system 300 can include a power supply 318 to power the components of the system 300.
In some embodiments the system 300 can include a display 316 with the housing 301. In some embodiments the display is external to the system. For example, the display data can be wirelessly transmitted to a device having a display, such as a computer, smartphone, tablet computer, flat screen monitor, television, etc. In some embodiments a tablet computer or smartphone 320 can be used with the system 300. The tablet computer 320 can include a processor 322 and display 324. In some embodiments the processor 322 can receive the measurement signal transmitted by the system 300 and analyze the measurement signal to determine properties associated with the measurement signal. In some embodiments the processor 322 is configured to receive data from the system 300 and display the data on the tablet computer 320 display 324. Decreasing the processing steps performed by the processor on board the system 300 can reduce the complexity and cost of the system 300.
Methods are also disclosed herein for providing instructions to the user to perform steps of calibration.
Humidifying the chemical colorimetric indicator can be done by providing a water or moisture source to the quantitative colorimetric measurement system. The water or moisture source can be used to humidify the chemical colorimetric indicator or film above a threshold humidification level. In some embodiments humidifying the chemical colorimetric indicator can include contacting the chemical colorimetric indicator with air exhaled by a user of the quantitative colorimetric measurement system. The air exhaled by the user of the quantitative colorimetric measurement system has a humidity level that can quickly and easily humidify the chemical colorimetric indicator. Humidifying can include contacting the chemical colorimetric material with air exhaled by the user for a set amount of time. For example, the chemical colorimetric material can be humidified after contacting it with exhaled air for several minutes. In some embodiments humidifying includes contacting the chemical colorimetric material with exhaled air for greater than about one minute. In some embodiments humidifying includes contacting the chemical colorimetric material with exhaled air for greater than about two minutes. In some embodiments humidifying includes contacting the chemical colorimetric material with exhaled air for about two minutes to about four minutes. In some embodiments humidifying includes contacting the chemical colorimetric material with exhaled air for greater than about four minutes.
In some embodiments water or moisture can be provided to the quantitative colorimetric measurement system to humidify the chemical colorimetric indicator. For example, the quantitative colorimetric measurement system can include a port configured to receive a water source, moisture source, or humidifier component. The introduction of water or moisture through the port can humidify the chemical colorimetric indicator and/or the gas passing through the system upstream of the chemical colorimetric indicator. In another example the introduction of the moisture or water can be used to wet a filter within the colorimetric system that can provide humidity to the gas passing through the system to humidify the chemical colorimetric indicator. The wet filter can also keep the chemical colorimetric indicator humidified during use of the system for a breathing therapy. The wet filter or other material can function as a humidity moisture exchanger (HME) to provide humidity to the air/gas passing through the wet filter.
In some embodiments humidifying the chemical colorimetric indicator includes contacting the first gas with a humidification source. For example, the first gas can be passed through a water or moisture source to mix the first gas with the water or moisture source to humidify the first gas and chemical colorimetric indicator. The water or moisture source can be provided with a removable cartridge containing the carbon dioxide calibration gas and the moisture source.
In some embodiments the humidification source can be provided with the reference gas. For example water or moisture can be provided within the container including the reference gas or in fluid communication with the gas conduit connecting the reference gas and chemical colorimetric indicator.
In some embodiments a hydrophilic super absorbent polymer (SAP) can be used to provide a humidity source. The SAP can be in the gas container or in the gas pathway with the cartridge containing the chemical colorimetric indicator. In some embodiments the humidification source can be provided with the cartridge having the chemical colorimetric indicator.
In some embodiments the chemical colorimetric indicator can be optionally humidified after measuring the first color of the chemical colorimetric indicator and prior to exposing the chemical colorimetric indicator to the second gas. Humidifying the chemical colorimetric indicator prior to exposing the indicator to the second gas can be done by contacting the chemical colorimetric indicator with air exhaled by a user of the quantitative colorimetric measurement system or any of the humidification methods disclosed herein.
Exposing the chemical colorimetric indicator to a second gas can include exposing the indicator to a sealed container filled with a reference sample having a known carbon dioxide concentration. In some embodiments the known carbon dioxide concentration is from about 4% to about 7% carbon dioxide. In some embodiments the sealed container filled with the reference sample having the known carbon dioxide concentration has a known humidity content.
In some embodiments exposing the indicator to the first gas includes exposing the colorimetric indicator to a sealed container filled with a reference sample having a known carbon dioxide concentration. The sealed container filled with the reference sample having the known carbon dioxide concentration can have a known humidity content. In some embodiments the first gas has a concentration of CO2 of about 0% to about 2%. In some embodiments exposing the indicator to the first gas includes exposing the colorimetric indicator to ambient air. Ambient air can be used to provide a reference source having a near zero concentration of carbon dioxide to calibrate the lower end of the span calibration for the chemical colorimetric indicator. In some embodiments the span calibration can be applied to a measurement of a color of the chemical colorimetric indicator exposed to a breath sample.
The calibration methods can include engaging a cartridge with the quantitative colorimetric measurement system with the cartridge containing the reference gas and the chemical colorimetric indicator. The methods can further include the patient using the quantitative colorimetric measurement system for a breathing therapy for up to seven days. In some cases the methods include replacing the chemical colorimetric indicator with a second chemical colorimetric indicator after about 5-7 days.
In some embodiments the chemical colorimetric indicator can be used for greater than 5-7 days. For example, the chemical colorimetric indicator can be recalibrated about every 5-7 days with the colorimetric indicator used for a total time period of a month or longer. In some embodiments the chemical colorimetric indicator can be used for 28 days or longer. For each recalibration the calibration steps described herein can be used to re-calibrate the colorimetric indicator. The span calibration data developed by exposing the colorimetric indicator to a reference gas and ambient air can be used to recalibrate the chemical colorimetric indicator after a period of use following an earlier calibration. After recalibration the user can continue to use the quantitative colorimetric system to provide a breathing therapy. In some cases the recalibration of the chemical colorimetric indicator could skip the humidification step because the film would already have a threshold level of humidity from the prior use of the film for the breathing therapy.
The humidification and calibration methods described herein can be applied to each fresh or new chemical colorimetric indicator that is used in the system. The colorimetric indicator can become contaminated or lose the responsiveness needed for the applications disclosed herein. A new colorimetric indicator can be engaged with the colorimetric system and calibrated. For example the calibration methods can include humidifying the second chemical colorimetric indicator, exposing the second chemical colorimetric indicator to a first gas, measuring a first color of the second chemical colorimetric indicator based on the exposure to the first gas, exposing the second chemical colorimetric indicator to a second gas, measuring a second color of the second chemical colorimetric indicator based on the exposure to the second gas having a different CO2 concentration than the first gas, and deriving a span calibration based on the difference between the first color of the second chemical colorimetric indicator and the second color of the second chemical colorimetric indicator. The calibration steps described herein can also determine when the chemical colorimetric indicator is performing poorly and needs to be replaced.
The methods disclosed herein can also include verifying the humidity of the chemical colorimetric indicator after humidifying the chemical colorimetric measurement system. Verifying the humidity of the chemical colorimetric indicator can also include measuring a color of a humidity sensor that is part of the colorimetric measurement system. In some embodiments verifying the humidity can include determining if the color of the humidity sensor corresponds to a humidity above a threshold humidity level. After the humidity of the chemical colorimetric indicator has been verified the span calibration or other calibration methods can be performed by exposing the chemical colorimetric indicator to the first and second gases.
In some embodiments a temperature adjustment or correction can also be applied to the interrogation of the color of the chemical colorimetric indicator. The methods described herein can include measuring a temperature of the chemical colorimetric indicator when measuring the color of the chemical colorimetric indicator. The method can further include applying a temperature adjustment or correction to the measured color based on the temperature of the chemical colorimetric indicator. For example the temperature can be used to calculate the carbon dioxide content of the sample gas in combination with the measured signal corresponding to the color of the chemical colorimetric indicator.
Initial characterization data determined using the various methods disclosed herein can be recorded for the tested chemical colorimetric indicator, in particular when the characterization is done prior to packaging the chemical colorimetric indicator. The methods can further include packaging the chemical colorimetric indicator. The initial characterization data for the chemical colorimetric indicator can be included with the packaged chemical colorimetric indicator. The characterization data can be encoded and included on or within the packaging for the chemical colorimetric indicator. The encoded information can be scanned or read by the quantitative measurement system or a hand held computing device in electronic communication with the quantitative measurement system, such as during the calibration procedure described above. Non limiting examples of encoding of the characterization data include: bar code, QR code, other machine readable, RFID, or cloud data transfer.
The initial characterization of the chemical colorimetric indicator can be used to determine a curve for the indicator's response to carbon dioxide.
The initial characterization of the indicator can include passing known carbon dioxide gas concentrations into contact with the indicator and measuring the response of the indicator. This is done for carbon dioxide concentrations from about 0% to about 8% CO2. The temperature dependence of the response of the indicator can also be observed. For example, the film can be subjected to multiple concentrations of carbon dioxide and a temperature controller can control the temperature of the indicator such that the indicator can be observed at multiple temperatures for each of the carbon dioxide concentrations. The indicator's response to the varying temperatures and carbon dioxide concentrations can be determined and considered the initial characterization of the film. The combination of the response data points to CO2 concentration and at various temperatures can then be turned into polynomial equations to describe the behavior of the indicator, such as converting a detected photodetector voltage to a corresponding carbon dioxide concentration. The characterization can include calculating and determining coefficients for the polynomial equations. Once film is characterized the coefficients can be used by a quantitative colorimetric measurement system as part of the calibration methods disclosed herein for the user to follow prior to using the device for a breathing therapy.
In some embodiments characterization of the indicator can include sequentially exposing the indicator to different concentrations of carbon dioxide across a range of temperatures within the operating range of the device. In one example the concentrations of carbon dioxide can be about 0, 1, 2, 4, 6, and 8% CO2 with temperatures across operating range (15-30° C.). In some embodiments the plurality of temperatures are between about 15° C. and 31° C. The corresponding voltage signal detected by the photodetector can be recorded for each of the different concentrations of carbon dioxide at each temperature and for each different wavelength or spectra reflected off of the chemical colorimetric indicator.
In some embodiments the function can be represented as: CO2(V)=[A′*V3]+[B′*V2]+[C′*V]+D′. Each of A′, B′, C′ and D′ can be a function of temperature. In some embodiments the function can be represented as: CO2(V,T)=[A′(T)*V3]+[B′(T)*V2]+[C′(T)*V]+D′(T) with A′(T)=a1*T2+b1*T+c1; B′(T)=a2*T2+b2*T+c2; C′(T)=a*T2+b3*T+c3; and D′(T)=a4*T2+b4*T+4.
In some embodiments the humidity of the chemical colorimetric indicator can be considered when interrogating the chemical colorimetric indicator. The humidity of the film can be determined using a humidity sensor, humidity probe, or other humidity detection device. The humidity sensor can be included within the device, such as on one or more of the printed circuit boards (PCB) on the device and/or removable cartridges. The humidity of the chemical colorimetric indicator can be applied to the voltage corresponding to the color of the chemical colorimetric indicator when the voltage is measured. In other embodiments the humidity can be applied as a humidity correction after obtaining the voltage measurement.
In some embodiments the humidity can be accounted for by using the following equation:
In some embodiments the measured voltage (i.e., color response) is multiplied by the relative humidity (RH) factor in the equation above, where p, q, and r are coefficients of the parabolic function and RH is the measured relative humidity in the system. The compensation can be used to normalize the voltage measured to correspond to an effective relative humidity of 60%.
The humidity application can be applied to all of the methods for interrogating the chemical colorimetric indicator described herein. For example, the humidity of the film can be applied to voltage measurements during the characterization of the film, calibration of the film, and during use of the system by the user.
The film characterization and coefficient calculation can be performed for each batch of film. The coefficients can be encoded with the packaging with a barcode, RFID, or other machine readable format. In some embodiments the coefficients can be stored in the cloud and downloaded by the system when the chemical colorimetric material is used.
The characterization and calibration methods can also include measuring a temperature of the chemical colorimetric indicator when measuring the color of the chemical colorimetric indicator based on the exposure to the first gas. The methods can also include applying a temperature correction to the first measurement signal based on the temperature of the chemical colorimetric indicator when measuring the color of the chemical colorimetric indicator.
Any of the characterization data determined in the laboratory or factory can be encoded with the colorimetric material as described herein. The properties and characteristics of the film, such as the response to carbon dioxide, can change over time when the film is stored. In some embodiments the colorimetric material can be re-calibrated prior to use by the patient.
The methods can include the user removing the colorimetric chemical indicator from a package containing the colorimetric indicator. The package containing the colorimetric indicator can include the factory characterization data for the colorimetric chemical indicator. The factory characterization data can be encoded such that a hand held computer or the quantitative colorimetric measurement system can scan or read the characterization data. The factory characterization data can refer to the characterization determined for the specific chemical colorimetric indicator determined at the factory or at the lab prior to packaging the indicator.
The user can engage the colorimetric chemical indicator with the quantitative colorimetric measurement system. After calibrating the chemical colorimetric material in the quantitative colorimetric measurement system the system is ready for use by the user. For example, the user can perform any of the methods and breathing therapies disclosed herein. In some embodiments the user can then humidify the chemical colorimetric indicator prior to exposing the chemical colorimetric indicator to the first gas.
The factory characterization data for the chemical colorimetric indicator can be compared to any of the calibration data developed using the methods disclosed herein. The calibration data and fit coefficients can be compared to the factory calibration and characterization data followed by adjusting the calibration data or curve for the film based on the calibration data at the time of use.
The calibration of the quantitative colorimetric measurement system can be adjusted based on the span calibration and factory characterization data. In some embodiments the characteristics and properties of the light sources can be adjusted such that the voltage response of the chemical colorimetric indicator to the reference gas and ambient air substantially matches the characterization data. In some embodiments other adjustments can be made to the system to match the voltage response of the chemical colorimetric indicator to the reference gas and ambient air to the characterization data. For example, one or more of the system signal processing, photodetectors, or other aspects of the system can be modified. Modifying the system properties to match the voltage response of the chemical colorimetric indicator to the characterization data can allow for the original characterization fit coefficients to be used by the system.
In some embodiments the system can perform an optimization of the LED to achieve similar voltage readings to the characterization for the reference gas concentration and ambient air. For example the derived coefficients and calibration curves can be used to calculate the carbon dioxide concentration from the measured voltage readings for the reference gas and the ambient air. The system hardware and software can then modify the LED drive to match the detector voltage levels based on the characterization data for the ambient air and reference gas at the recorded temperature. In some embodiments optimizing the LED drive can include matching the voltage difference between the ambient air and reference gas at the recorded temperature. The adjustments in the drive, offsets, and gains for the LED can be made by the system such that the original characterization fit coefficients can be used to calculate the CO2 concentration based on the measured voltages and temperatures. In some embodiments modifying the LED drive can include adjusting the electrical current supplied to the light source/LED.
In some embodiments the factory characterization data can include a span calibration for carbon dioxide exposure to the chemical colorimetric indicator. The span calibration can be as described herein, including humidification of the colorimetric indicator and exposure to gases with varying carbon dioxide concentrations. The methods can include comparing the span CO2 calibration to the calibration data and/or factory characterization data. The calibration curve for the colorimetric indicator can be adjusted based on the comparison of the factory characterization data with calibration data prior to using the colorimetric indicator.
In some embodiments temperature corrections can also be applied during the factory characterization and calibration performed just prior to using the colorimetric indicator in the quantitative measurement system.
The breathing therapy methods can include outputting a set of visual and/or audio cues from the quantitative colorimetric system with instructions for the user to adjust their breathing pattern to coincide with the cues to thereby modify the user's exhaled CO2 levels. In some embodiments the breathing pattern includes the exhaled CO2 level and respiration rate. In some embodiments displaying the user's measured CO2 levels to provide visual feedback during treatment. In some embodiments displaying the user's breathing rate to provide visual feedback during treatment. In some embodiments the therapy directs the user's end-tidal CO2 levels to a level between about 37 mmHg and 43 mmHg. The breathing therapy methods can include treating post-traumatic stress disorder (PTSD), panic disorder, anxiety, asthma, hypertension, obsessive-compulsive disorder, social phobia, depression, apnea, migraines, or epilepsy by training the user to modify their exhaled CO2 levels. In some embodiments the temperature of the chemical colorimetric indicator can be measured during the breathing therapy. A temperature correction can be applied to the measured voltage.
In addition to the above, various aspects of the inventions are directed to a breathing therapy system for non-invasively and non-pharmaceutically treating various conditions include panic disorder, anxiety, general anxiety disorder, obsessive-compulsive disorder, social phobia, depression, apnea, migraines, epilepsy, asthma, post-traumatic stress disorder, and hypertension. Some embodiments described herein are directed toward breathing therapy to treat a disorder or disease. For example, quantitative colorimetric carbon dioxide measurement system described can be used to measure and modify a user's CO2 levels to provide treatment for any number of disorders or illnesses.
A variety of different configurations for cartridges including colorimetric chemical indicators are also disclosed herein. The cartridge can include a gas measurement chamber and the chemical colorimetric indicator. Some embodiments include a cartridge comprising a colorimetric chemical indicator with the cartridge configured to removably engage with a quantitative colorimetric measurement system and a sealed container comprising a reference gas comprising a known concentration of carbon dioxide. In some embodiments the known carbon dioxide concentration can be from about 4% to about 7% carbon dioxide.
In some embodiments the sealed container is configured for a single use. In some embodiments the sealed container can be configured for multiple uses. In some embodiments the sealed container is configured to be resealable. In some embodiments the sealed container is integral with the cartridge. In some embodiments the sealed container is separate from the cartridge. In some embodiments the sealed container contains a known humidity content.
In some embodiments a reusable sealed container with the reference gas can be part of a reference gas station. The reference gas station can be used to provide the reference gas to the quantitative colorimetric measurement system by the user. The reference gas station can dock with the system to provide the reference gas. The gas station can be used multiple times to calibrate the quantitative colorimetric measurement system. In some cases the reference gas station can also include a humidifier. The humidifier can be used to humidify the colorimetric indicator.
The reusable sealed container can have a volume sufficient to hold enough gas to calibrate the chemical colorimetric material one or more times. In some embodiments the reusable sealed container has a volume of greater than about 50 ml. In some embodiments the reusable sealed container has a volume that is less than about 100 ml.
In some embodiments the cartridge can include a second sealed container having a second known concentration of carbon dioxide. The second known concentration of carbon dioxide can be less than about 2% carbon dioxide. In some cases the second sealed container contains a known humidity content.
In some embodiments the cartridge can include a humidification module configured to humidify an incoming gas prior to the gas contacting the colorimetric chemical indicator. In some embodiments the humidification module includes a humidity reservoir. In some embodiments the humidification module includes a wet filter, hydrophilic absorbent material, super absorbent polymer (SAP), or humidity-moisture exchanger (HME). In some embodiments the humidification module includes a water reservoir.
In some embodiments the cartridge includes a humidity sensor.
The cartridges can be used with the quantitative colorimetric measurement systems disclosed herein. The quantitative colorimetric measurement system can include an electro-optical sensor assembly including one or more light sources and a photodiode configured to detect light reflected off of the chemical colorimetric indicator by the light source. The electro-optical sensor assembly can be configured to generate an electrical signal based on the light detected by the photodiode. The system can include a processor in communication with the electro-optical sensor assembly. The processor can be configured to receive the electrical signals generated by the electro-optical sensor assembly. The processor can use the signals to compute the quantity of carbon dioxide exposed to the chemical colorimetric indicator. The processor can be integral with the quantitative colorimetric measurement system or part of a hand held computing device.
The chemical colorimetric indicator is adapted to change color in response to exposure to a quantity of carbon dioxide gas. In some embodiments the colorimetric indicator uses m-cresol purple. In some embodiments the chemical colorimetric indicator can be formulated or configured to change color in response to other chemicals. For example, the chemical colorimetric indicator can be configured to measure the amount of carbon dioxide in a solution with water or other solvent. In some cases the chemical colorimetric indicator can be configured to measure hydrocarbons (CxHy).
The electro-optical assembly can also be configured to detect light reflected off of a humidity sensor that is part of the removable cartridge or other part of the quantitative colorimetric measurement system. The humidity sensor can be adapted to change color in response to exposure to humidity. In some embodiments the humidity sensor is downstream of the colorimetric chemical indicator. In some embodiments the humidity sensor is upstream of the colorimetric chemical indicator.
The present application also includes kits including any of the components disclosed herein. In some embodiments kits are provided including a chemical colorimetric indicator configured to be used with a quantitative carbon dioxide measurement system described herein along with any of the characterization and calibration data for the chemical colorimetric indicator described herein. In some embodiments the kits include factory characterization data corresponding to the span calibration performed for the colorimetric indicator. In some embodiments the characterization data includes coefficients for a calibration curve. The calibration curve can be a polynomial equation as described herein. The coefficients can correspond to any of the polynomial equations described herein. In some embodiments the coefficients can include coefficients for a temperature sensitive equation. In some embodiments the calibration curve is a function of a voltage measured by the quantitative carbon dioxide measurement system. In some embodiments the kit can further include a sealed packaging material containing the chemical colorimetric indicator. In some embodiments the packaging material is moisture resistant and light resistant. In some embodiments the characterization data is encoded on the packaging of the chemical colorimetric indicator in a machine readable format.
When a feature or element is herein referred to as being “on” another feature or element, it can be directly on the other feature or element or intervening features and/or elements may also be present. In contrast, when a feature or element is referred to as being “directly on” another feature or element, there are no intervening features or elements present. It will also be understood that, when a feature or element is referred to as being “connected”, “attached” or “coupled” to another feature or element, it can be directly connected, attached or coupled to the other feature or element or intervening features or elements may be present. In contrast, when a feature or element is referred to as being “directly connected”, “directly attached” or “directly coupled” to another feature or element, there are no intervening features or elements present. Although described or shown with respect to one embodiment, the features and elements so described or shown can apply to other embodiments. It will also be appreciated by those of skill in the art that references to a structure or feature that is disposed “adjacent” another feature may have portions that overlap or underlie the adjacent feature.
Terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. For example, as used herein, the singular forms “a”, “an” and “the” are intended to include the plural forms as well, unless the context clearly indicates otherwise. It will be further understood that the terms “comprises” and/or “comprising,” when used in this specification, specify the presence of stated features, steps, operations, elements, and/or components, but do not preclude the presence or addition of one or more other features, steps, operations, elements, components, and/or groups thereof. As used herein, the term “and/or” includes any and all combinations of one or more of the associated listed items and may be abbreviated as “/”.
Spatially relative terms, such as “under”, “below”, “lower”, “over”, “upper” and the like, may be used herein for ease of description to describe one element or feature's relationship to another element(s) or feature(s) as illustrated in the figures. It will be understood that the spatially relative terms are intended to encompass different orientations of the device in use or operation in addition to the orientation depicted in the figures. For example, if a device in the figures is inverted, elements described as “under” or “beneath” other elements or features would then be oriented “over” the other elements or features. Thus, the exemplary term “under” can encompass both an orientation of over and under. The device may be otherwise oriented (rotated 90 degrees or at other orientations) and the spatially relative descriptors used herein interpreted accordingly. Similarly, the terms “upwardly”, “downwardly”, “vertical”, “horizontal” and the like are used herein for the purpose of explanation only unless specifically indicated otherwise.
Although the terms “first” and “second” may be used herein to describe various features/elements, these features/elements should not be limited by these terms, unless the context indicates otherwise. These terms may be used to distinguish one feature/element from another feature/element. Thus, a first feature/element discussed below could be termed a second feature/element, and similarly, a second feature/element discussed below could be termed a first feature/element without departing from the teachings of the present invention.
As used herein in the specification and claims, including as used in the examples and unless otherwise expressly specified, all numbers may be read as if prefaced by the word “about” or “approximately,” even if the term does not expressly appear. The phrase “about” or “approximately” may be used when describing magnitude and/or position to indicate that the value and/or position described is within a reasonable expected range of values and/or positions. For example, a numeric value may have a value that is +/−0.1% of the stated value (or range of values), +/−1% of the stated value (or range of values), +/−2% of the stated value (or range of values), +/−5% of the stated value (or range of values), +/−10% of the stated value (or range of values), etc. Any numerical range recited herein is intended to include all sub-ranges subsumed therein.
Although various illustrative embodiments are described above, any of a number of changes may be made to various embodiments without departing from the scope of the invention as described by the claims. For example, the order in which various described method steps are performed may often be changed in alternative embodiments, and in other alternative embodiments one or more method steps may be skipped altogether. Optional features of various device and system embodiments may be included in some embodiments and not in others. Therefore, the foregoing description is provided primarily for exemplary purposes and should not be interpreted to limit the scope of the invention as it is set forth in the claims.
The examples and illustrations included herein show, by way of illustration and not of limitation, specific embodiments in which the subject matter may be practiced. As mentioned, other embodiments may be utilized and derived there from, such that structural and logical substitutions and changes may be made without departing from the scope of this disclosure. Such embodiments of the inventive subject matter may be referred to herein individually or collectively by the term “invention” merely for convenience and without intending to voluntarily limit the scope of this application to any single invention or inventive concept, if more than one is, in fact, disclosed. Thus, although specific embodiments have been illustrated and described herein, any arrangement calculated to achieve the same purpose may be substituted for the specific embodiments shown. This disclosure is intended to cover any and all adaptations or variations of various embodiments. Combinations of the above embodiments, and other embodiments not specifically described herein, will be apparent to those of skill in the art upon reviewing the above description.
The present application claims priority to U.S. Application Ser. No. 62/171,192 filed on Jun. 4, 2015 titled “Devices and Methods for Calibrating a Colorimetric Sensor” and U.S. Application Ser. No. 62/322,623 filed on Apr. 14, 2016 titled “Devices and Methods for Calibrating a Colorimetric Sensor” each of which is herein incorporated by reference in its entirety.
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/US16/35613 | 6/3/2016 | WO | 00 |
| Number | Date | Country | |
|---|---|---|---|
| 62171192 | Jun 2015 | US | |
| 62322623 | Apr 2016 | US |
