A breath nitric oxide measurement device

Abstract

The application relates to an exhaled nitric oxide measuring device which comprises a flow control device (100), a flow sensor (200), a gas analysis device (800) and a control unit (900). The flow control device is used for adjusting and controlling multiple flow sections, and the device is integrated with the analysis device, so that the internal volume of the device is reduced, and the cost of the device is reduced due to high integration.

Description

Technical Field

[0001] This invention relates to a device for measuring exhaled nitric oxide. Background Technology

[0002] Exhaled nitric oxide (NO) measures the gaseous signaling molecules secreted by inflammatory cells in the respiratory tract, and can be used as a marker of airway inflammation for the detection of inflammation in respiratory diseases. With the development of technology and the expansion of its application fields, a dynamic mathematical model of NO in the lungs, also known as extended NO analysis, has been gradually established.

[0003] The 2017 ERS Technical Standards for Expiratory Biomarkers in Lung Disease mentions methods for detecting NO in the alveoli and surrounding airways. NO detection at low flow rates primarily reflects the NO concentration in the large airways and is not sensitive to changes in NO in the small airways and alveoli surrounding the lungs. Mathematical models of lung dynamics, sometimes called extended NO analysis, are based on a simple two-chambered lung model. Simply put, this model consists of bronchi and alveoli. To refine the model, it considers an increased peripheral lung cross-sectional area and NO retrograde diffusion from the bronchi into the alveoli. Different mathematical analysis methods are used to refine the dynamic NO estimation.

[0004] 1) Nonlinear Model: At least three expiratory flow rates are required: low flow (≤20 mL / s), medium flow (100 mL / s), and high flow (350 or 400 mL / s). Measure at least twice at each flow rate, take the minimum value, and use the average flow rate and NO concentration to calculate the final NO parameter. FeNO50 can be estimated. When the NO parameter conforms to the nonlinear model, if the estimated FeNO50 differs from the actual measured FeNO50 by less than 5 ppb, then a lower flow rate can be used for adults and children who have difficulty controlling high-flow-rate exhalation.

[0005] 2) Linear Model: In practice, the linear model requires measuring and comparing FeNO50 beforehand, but this doesn't need to be substituted into the formula. Testing is performed at three expiratory flow rates, with a minimum flow rate of 100 mL / s and a maximum flow rate of 350 mL / s or even 400 mL / s. Each flow rate is tested twice. For children who cannot undergo high-flow-rate expiratory testing, a low flow rate, such as 250 mL / s, can be used. The NO output value for each test is recorded by calculating the flow rate and the corresponding NO value. A NO regression curve is plotted against the flow rate. The most important value of calculating CaNO using the NO model lies in assessing small airway and peripheral lung inflammation in patients with respiratory diseases and interstitial lung disease. JawNO is correlated with FeNO50, therefore it doesn't add additional clinical value to FeNO50, but the components of JawNO, CawNO and DawNO, help to better understand the relationship between increased airway NO production.

[0006] To reduce the difficulty of expiratory flow control and expand the applicable population for expiratory tests, devices that regulate expiratory flow are typically used to assist subjects in completing compliant expiratory tests. For example, current commercial technologies (such as Aerocrine's patent CN105916538A and Sunvou's patent N103487295B) and non-commercial technologies (such as other published patents CN203539351U, US9687178B2, CN207662681U, CN107961042A, and CN101458250A) provide self-regulating or electrically powered devices for constant expiratory flow, but they cannot simultaneously provide expiratory sampling at different flow rates; adjustments to the device's expiratory resistance settings are required to achieve this.

[0007] Different expiratory flow rates require different expiratory pressures. An expiratory pressure of at least 5 cmH2O is needed to close the soft palate, while a pressure no greater than 20 cmH2O is required to improve sampling success. To achieve both low-flow-rate (50 ml / s) and high-flow-rate (200 ml / s and above) expiratory sampling within the same instrument, in addition to a channel suitable for low-flow-rate sampling and control valves at both ends, a shunt channel and shunt control valve are typically required to provide sampling suitable for higher flow rates. The need for multiple control valves results in high costs and a relatively large size, preventing miniaturization.

[0008] In addition, the mainstream existing exhaled gas detection technologies all collect the gas into a gas storage device and then use a pump to continuously deliver the collected gas to the gas sensor at a smaller flow rate. The detection equipment is relatively large and requires a long time to eliminate interfering gases.

[0009] The existing technologies described above have the following problems:

[0010] 1. It cannot provide multiple flow rate adjustment functions; it does not support more than three flow rate adjustment functions.

[0011] 2. Miniaturization is not possible. To meet the regulation functions of more than two flow rates, multiple flow control valves are required, and a large gas storage device and analysis pump are also needed for detection.

[0012] 3. To satisfy more than two flow regulation functions, multiple flow control valves are required, which is costly.

[0013] The exhaled nitric oxide measuring device of the present invention can adjust and control multiple flow segments through a flow regulating device, and can also realize multiple functions such as offline sampling and nasal aspiration sampling. It also integrates an analysis device, reducing the internal volume of the instrument. The high integration and miniaturization reduce the cost and size of the instrument. Summary of the Invention

[0014] The present invention addresses the aforementioned problems by proposing an exhaled nitric oxide measurement device that integrates multiple flow rate segments for adjustment and control within a single flow rate regulating device. This reduces the difficulty of exhaled breath sampling during patient sampling, improves the success rate of multiple exhaled flow rate sampling, and ensures accurate and reliable test results. Furthermore, the integrated analysis device within the flow rate regulating device reduces the internal volume of the instrument, and this high level of integration lowers the cost of the instrument.

[0015] The exhaled nitric oxide measuring device proposed in this invention comprises a flow control device (100), a flow sensor (200), a gas analysis device (800), and a control unit (900). The flow control device consists of a dual-head stepper motor (101), a crankshaft (102), a piston (103), a support base (104), an end cap (105), a flow divider plate (107), a dynamic sealing gasket (108), and a valve core assembly. The valve core assembly is disposed in a sealed cavity formed by the support base (104), the end cap (105), the flow divider plate (107), and the dynamic sealing gasket (108). The dual-head stepper motor (101) is fixedly installed on the support base (104). The dual-head stepper motor (101) has two heads. One head is rotatable and connected to the crankshaft (102) to drive the crankshaft (102) to rotate. The other head is axially extendable and connected to the piston (103) to push the piston (103) to move linearly.

[0016] The valve core assembly (110) has at least two valve cores, and each valve core is provided with a return spring.

[0017] The end cap (105) is provided with an air inlet or outlet interface; the support base (104) is provided with a vent (303), a gas storage chamber (304), and a cavity (307), the cavity (307) and the gas storage chamber (304) being connected through the vent (303); the gas analysis device (800) is installed at the outlet of the gas storage chamber (304). Figure 2 As shown.

[0018] The crankshaft (102) has at least three different angle positions. By rotating the crankshaft (102) to different angles, the gas through the inlet diameter can be changed, thereby achieving adjustment and control of multiple flow segments.

[0019] The flow sensor (200) is located at the air inlet of the end cap and is used to monitor the flow rate during the entire sampling process and feed it back to the control unit (900). The control unit (900) is used to control the sampling and analysis processes of the exhaled nitric oxide measuring device.

[0020] The piston (103) is the same size and shape as the cross section of the gas storage chamber. The dual-head stepper motor drives the piston to make telescopic movements in the gas storage chamber, which helps to collect or push the collected gas to the gas analysis device.

[0021] During exhalation sampling, the gas passes through the flow control device (100) to control and collect the gas under different flow conditions required, and the flow sensor (200) provides real-time feedback. The gas passes through the vent (303) to the gas storage chamber (304). The dual-head stepper motor drives the piston (103) to transport the gas to the gas analysis device (800) for gas concentration analysis. The control unit (900) realizes the adjustment, collection, venting, and gas concentration analysis of the gas flow, realizing the function of adjusting and controlling multiple flow segments in one flow control device, and collecting and analyzing gas.

[0022] Furthermore, a one-way valve (112) can be installed at the end of the gas storage chamber (304). By driving the piston to move linearly to one side of the stepper motor through a dual-head stepper motor, a certain gas extraction flow rate is set to draw gas into the gas storage chamber, realizing functions such as offline sampling and nasal aspiration sampling.

[0023] By using the above multi-functional integrated devices, costs can be greatly controlled, achieving high functionality at low cost.

[0024] As described above, the device of this invention, through its integrated design, can achieve multiple flow rate adjustment functions, enabling the adjustment of three or more flow rates. It also simplifies components such as pumps, valves, gas chambers, and pipelines, achieving a miniaturized effect. This multi-functional integrated device significantly controls costs, achieving high functionality at a low cost. Its integration, low cost, and ease of commercialization allow it to meet diverse nitric oxide testing needs.

[0025] These and other features will become more clearly understood from the following detailed description in conjunction with the accompanying drawings and claims. Attached Figure Description

[0026] Figure 1 Block diagram of the device of the present invention.

[0027] Figure 2 Exploded view of the flow control device of the present invention.

[0028] Figure 3 A schematic diagram of the flow control device of the present invention in one state.

[0029] Figure 4 A schematic diagram of the flow control device of the present invention in state two.

[0030] Figure 5 A schematic diagram of the flow control device of the present invention in state three.

[0031] Figure 6 A schematic diagram of the flow control device of the present invention in state four.

[0032] Figure 7 A schematic diagram of the air extraction device of the present invention.

[0033] Figure 8 A schematic diagram of the air-pushing device of the present invention.

[0034] Figure 9 Schematic diagram of specific embodiment 3 of the present invention. Detailed Implementation Specific Implementation Example 1:

[0036] The exhaled nitric oxide measuring device of this embodiment consists of a flow control device (100), a flow sensor (200), a gas analysis device (800), and a control unit (900). The flow control device consists of a dual-head stepper motor (101), a crankshaft (102), a piston (103), a support base (104), an end cap (105), a flow divider plate (107), a dynamic sealing gasket (108), and a valve core assembly. The valve core assembly is disposed in the sealed cavity formed by the support base (104), the end cap (105), the flow divider plate (107), and the dynamic sealing gasket (108). The valve core assembly consists of two valve cores, one (110a) and two valve cores (110b). The end cap (105) is provided with an air inlet (302) and a diverter (301); the support base (104) is provided with a vent (303), a gas storage chamber (304) and a cavity (307), and the cavity (307) and the gas storage chamber (304) are connected through the vent (303). The gas analysis device (800) is installed at the outlet of the gas storage chamber (304); the flow sensor (200) is located at the air inlet (302).

[0037] In this embodiment, the crankshaft (102) of the flow control device has three different angular positions and three execution states, as follows:

[0038] State 1: When the dual-head stepper motor (101) is in its original zero-point state, such as Figure 3 As shown. At this time, the protrusions on the crankshaft (102) do not act on valve core one (110a) and valve core two (110b), so valve core one (110a) and valve core two (110b) are subjected to the force of the return spring (109). At this time, valve core one (110a) and valve core two (110b) are at zero point, and all interfaces and channels on the flow control device (100) are in the closed state. This state applies when the device of the present invention is not in use or when the sampling analysis is completed.

[0039] State 2: The dual-head stepper motor (101) rotates 90° counterclockwise from the zero position, as shown below. Figure 4As shown. A dual-head stepper motor (101) drives the crankshaft (102) to rotate. The protruding point on the crankshaft (102) corresponding to the position of valve core one (110a) acts on valve core one (110a), causing valve core one (110a) to move upward. At this time, a gap is generated between valve core one (110a) and the flow divider plate. Valve core two (110b) is in the zero point state, so valve core two (110b) is in the closed state. First, the venting mode is turned on, the piston (103) stays in the rightmost position, and the gas enters the interior through the air inlet (302) on the flow control device (100), passes through the gap between valve core one (110a) and the flow divider plate (107), and reaches the chamber (307). It reaches the gas storage chamber (304) through the vent (303), and the gas enters the gas analysis device (800) through the outlet of the gas storage chamber (304) and is discharged. After venting, the dual-head stepper motor (101) drives the piston (103) to move linearly to the left. The gas passes through the vent (303) to the gas storage chamber (304). Part of the gas enters the gas analyzer (800) through the gas storage chamber outlet and is discharged, while the rest remains in the gas storage chamber. Gas collection is completed within a set time. After gas collection is completed, the analysis stage begins, such as... Figure 7 As shown, at this time, the dual-head stepper motor (101) drives the crankshaft (102) to return to the zero point state, all interfaces and channels on the flow control device (100) are closed, and the dual-head stepper motor (101) drives the piston (103) to move linearly to the right. At this time, the one-way valve opens and pushes the collected gas to the gas analysis device (800) for analysis and to obtain the results. After the analysis is completed, as shown... Figure 8 As shown, the dual-head stepper motor (101) drives the piston (103) back to the initial state. State 2 is applicable when the device of the present invention is in the active sampling of the subject, such as exhalation sampling with a flow rate of 20 mL / s, 50 mL / s, or 100 mL / s.

[0040] State 3: The dual-head stepper motor (101) rotates 180° counterclockwise from the zero position, as shown below. Figure 5As shown. A dual-head stepper motor (101) drives the crankshaft (102) to rotate. The protruding points on the crankshaft (102) corresponding to valve core one (110a) and valve core two (110b) act on valve core one (110a) and valve core two (110b), causing valve core one (110a) and valve core two (110b) to move upward. First, the venting mode is opened, and gas enters the interior through the air inlet (302) on the flow control device (100) and passes through valve core one. A large portion of the gas passes through the gap between valve core 2 (110b) and the diversion partition plate (107) and enters the diversion port (301) for diversion; another portion reaches the chamber (307), and reaches the gas storage chamber (304) through the vent (303). The piston (103) stays at the rightmost position, and the gas enters the gas analysis device (800) through the outlet of the gas storage chamber (304) and is discharged. After evacuation, the dual-head stepper motor (101) drives the piston (103) to move linearly to the left. Gas enters the interior through the inlet (302) on the flow control device (100), passes through the gap between valve core one (110a) and the flow divider plate, and a large portion passes through the gap between valve core two (110b) and the flow divider plate (107) to enter the flow divider (301) for diversion. Another portion reaches the chamber (307), and through the vent (303) reaches the gas storage chamber (304). Part of this part enters the gas analyzer (800) through the outlet of the gas storage chamber (304) and is discharged, while part remains in the gas storage chamber. Gas collection is completed within a set time. After gas collection is completed, the analysis stage begins, such as... Figure 7 As shown, at this time, the dual-head stepper motor (101) drives the crankshaft (102) to return to the zero point state, all interfaces and channels on the flow control device (100) are closed, and the dual-head stepper motor (101) drives the piston (103) to move linearly to the right. At this time, the one-way valve opens and pushes the collected gas to the gas analysis device (800) for analysis and to obtain the results. After the analysis is completed, as shown... Figure 8 As shown, the dual-head stepper motor (101) drives the piston (103) back to the initial state. State 3 is applicable when the device of the present invention is in the process of active high-flow sampling by the subject, such as expiratory sampling with a flow rate of 200 mL / s, 300 mL / s, or 450 mL / s.

[0041] This embodiment can realize online oral-expiratory sampling and analysis in closed state, with low expiratory flow (e.g., 20mL / s, 50mL / s, 100mL / s), and with high expiratory flow (e.g., 200mL / s, 300mL / s, 450mL / s). It can also be combined to realize functions such as upper and lower airway sampling and analysis, and large and small airway sampling and analysis. Specific Implementation Example 2:

[0043] This embodiment utilizes Figure 2 The exploded view of the device shown shows an exhaled nitric oxide measuring device, in which the valve core assembly consists of two valve cores. The valve core assembly is located in a sealed cavity composed of a support base (104), an end cap (105), a flow divider plate (107), and a dynamic sealing gasket (108); to increase the sealing performance of the end cap (105) and the flow divider plate (107), a sealing gasket (106) can be added. Both the dynamic sealing gasket (108) and the sealing gasket (106) are made of flexible materials, such as silicone or fluororubber. The end cap (105) is provided with an air inlet (302) and a flow divider (301); the support base (104) is provided with a vent (303), a gas storage chamber (304), and a cavity (307), and the cavity (307) and the gas storage chamber (304) are connected through the vent (303). A one-way valve (112) and a gas analysis device (800) are installed at the end of the gas storage chamber (304); a flow sensor (200) is located at the air inlet (302).

[0044] The inlet (302) has a designed diameter of 4mm, the diversion port (301) has a designed diameter of 3mm, the annular gap between valve core one (110a) and diversion partition plate (107) has a designed maximum diameter of 2mm, and the annular gap between valve core two (110b) and diversion partition plate (107) has a designed maximum diameter of 3mm. The flow control device (100) has a height of 45mm, a length of 50mm, and a width of 40mm; the dual-head stepper motor (101) has an axial stroke of 20mm; and the air storage chamber (304) has a set volume of 30mL.

[0045] In this embodiment, the crankshaft (102) of the flow control device has four different angular positions and four execution states, as follows:

[0046] State 1: The dual-head stepper motor (101) is in its original zero-point state. Valve core one (110a) and valve core two (110b) are at zero point, and all interfaces and channels on the flow control device (100) are closed. This state applies when the device of the present invention is not in use or when sampling and analysis are completed.

[0047] State 2: The dual-head stepper motor (101) rotates 90° counterclockwise at the zero position. A gap is created between valve core 1 (110a) and the diversion partition plate (107), with a diameter of 2mm. Valve core 2 (110b) is in the zero position, so valve core 2 (110b) is in the closed state. Gas passes through the gap and reaches the chamber (307), and then through the vent (303) into the gas storage chamber (304) to complete gas collection and analysis.

[0048] If the subject uses oral expiratory breath sampling at a flow rate of 50 mL / s, the expiratory resistance is 11.5 cmH2O (meeting the international technical standards for oral or nasal expiratory breath sampling and analysis of endogenous NO established by the American Thoracic Society (ATS) and the European Respiratory Society (ERS) in 2005: the oral expiratory pressure must exceed 5 cmH2O during testing, the soft palate connecting the upper and lower respiratory tracts must be closed to avoid mixing of gases from the upper and lower respiratory tracts). Therefore, nitric oxide testing and analysis can be performed using oral expiratory breath sampling, primarily from the large airways.

[0049] State 3: The dual-head stepper motor (101) rotates 180° counterclockwise from the zero position. At this time, a gap is formed between valve core 1 (110a) and the diversion partition plate (107), with a gap diameter of 2mm; a gap is formed between valve core 2 (110b) and the diversion partition plate (107), with a gap diameter of 3mm; since the gap between valve core 2 (110b) and the diversion partition plate (107) is larger than the gap between valve core 1 (110a) and the diversion partition plate (107), most of the gas is discharged through the vent port; the remaining gas reaches the chamber (307) through the gap between valve core 1 (110a) and the diversion partition plate (107), and reaches the gas storage chamber (304) through the vent (303) to complete gas collection and analysis.

[0050] If the subject uses an oral breath sample taken at a flow rate of 200 mL / s, the expiratory resistance is 10.8 cmH2O (meeting the international technical standards for oral or nasal breath sampling and analysis of endogenous NO established by the American Thoracic Society (ATS) and the European Respiratory Society (ERS) in 2005: the oral expiratory pressure must exceed 5 cmH2O during testing, the soft palate connecting the upper and lower respiratory tracts must be closed to avoid mixing of gases from the upper and lower respiratory tracts). Therefore, nitric oxide testing and analysis can be performed using oral breath sampling with small airways as the primary pathway.

[0051] State 4: The dual-head stepper motor (101) rotates 90° clockwise from the zero position, as shown below. Figure 6As shown. The dual-head stepper motor (101) drives the crankshaft (102) to rotate. The protruding point on the crankshaft (102) corresponding to the position of valve core one (110a) acts on valve core one (110a), causing valve core one (110a) to move upward. A gap is generated between valve core one (110a) and the diversion partition plate (107). At this time, the height of the protruding point is lower than that in state two, and the gap between valve core one (110a) and the diversion partition plate (107) is smaller than that in state two. The gap diameter is 1mm. Valve core two (110b) is in the zero point state, so valve core two (110b) is in the closed state. Simultaneously, the dual-head stepper motor (101) drives the piston (103) to move linearly to the left. The one-way valve (112) is closed, and the gas enters the interior through the air inlet (302) on the flow control device (100), passes through the gap between the valve core (110a) and the diversion partition plate (107), and reaches the chamber (307). It then reaches the gas storage chamber (304) through the vent (303). Gas collection is completed within the set time, and then analysis is performed. The pumping flow rate can be set to 2-20 mL / s as needed.

[0052] At this point, offline aspiration sampling and analysis can be performed; if the subject's mouth is equipped with a whistle with resistance greater than 5 cmH2O and blows it simultaneously, passive aspiration sampling at a flow rate of 10 mL / s can be performed, and nasal aspiration sampling and nitric oxide testing and analysis can be performed.

[0053] This embodiment can achieve various modes including closed mode, 10mL / s offline or nasal aspiration sampling and analysis, 50mL / s online oral-expiratory breath sampling and analysis, and 200mL / s online oral-expiratory breath sampling and analysis. It can also be combined to achieve functions such as upper and lower airway sampling and analysis, large and small airway sampling and analysis, and triple analysis. Through the design of the inlet diameter and gap dimensions, it meets international technical standards and fulfills clinical needs.

[0054] In this embodiment, a multi-functional integrated device is used to realize a flow regulation device that replaces 3 to 5 valve groups, pumps, air chambers, pipelines, etc., thus meeting the requirement of miniaturization. Compared with the existing solutions using single solenoid valves + pumps, the cost can be reduced to 1 / 3; the volume can be reduced to 1 / 2. Specific Implementation Example 3:

[0056] This embodiment utilizes Figure 9 The schematic diagram of the device shown is assembled into an exhaled nitric oxide measuring device, in which the valve core group consists of 3 valve cores. The crankshaft (102) is respectively set with protrusion points corresponding to the positions of valve core one (110a), valve core two (110b), and valve core three (110c), which can act on each valve core respectively; the end cap (105) is added with a diversion port two (303) corresponding to valve core three (110c).

[0057] Adding a valve core can further refine the expiratory flow rate range, allowing for appropriate expiratory resistance even with online oral expiratory sampling at flow rates of 300 mL / s or even 450 mL / s. This helps reduce the difficulty of expiratory sampling and improves the success rate and accuracy of multiple expiratory flow rate sampling.

[0058] This invention is not limited to the embodiments shown and described, but any variations and modifications are within the scope of the appended claims.

Claims

1. A breath nitric oxide measuring device, comprising a flow control device (100), a flow sensor (200), a gas analysis device (800), and a control unit (900), characterized in that: The flow control device consists of a dual-head stepper motor (101), a crankshaft (102), a piston (103), a support base (104), an end cap (105), a flow divider plate (107), a dynamic sealing gasket (108), and a valve core assembly (110). The valve core assembly is located in the sealed cavity formed by the support base (104), the end cap (105), the flow divider plate (107), and the dynamic sealing gasket (108). The dual-head stepper motor (101) is fixedly installed on the support base (104). The dual-head stepper motor (101) has two heads. One head is rotatable and connected to the crankshaft (102) to drive the crankshaft (102) to rotate. The other head is axially extendable and connected to the piston (103) to push the piston (103) to move linearly. The gas analysis device (800) is installed on the flow control device (100). The crankshaft (102) has at least three different angle positions. By rotating the crankshaft (102) to different angles, the gas through the inlet diameter can be changed, thereby achieving adjustment and control of multiple flow segments.

2. The exhaled nitric oxide measuring device as described in claim 1, characterized in that: The valve core assembly (110) has at least two valve cores, and each valve core is provided with a return spring.

3. The exhaled nitric oxide measuring device as described in claim 1, characterized in that: The end cap (105) is provided with an air inlet or outlet interface; the support base (104) is provided with a vent (303), a gas storage chamber (304) and a cavity (307), and the cavity (307) and the gas storage chamber (304) are connected through the vent (303); the gas analysis device (800) is installed at the outlet of the gas storage chamber (304).

4. The exhaled nitric oxide measuring device as described in claim 1, characterized in that: The flow sensor (200) is located at the air inlet of the end cap and is used to monitor the flow rate during the entire sampling process and feed it back to the control unit (900). The control unit (900) is used to control the sampling and analysis processes of the exhaled nitric oxide measuring device.

5. The exhaled nitric oxide measuring device as described in claim 1, characterized in that: The piston (103) is the same size and shape as the cross section of the gas storage chamber. The dual-head stepper motor drives the piston to make telescopic movements in the gas storage chamber, which helps to collect or push the collected gas to the gas analysis device.

6. The exhaled nitric oxide measuring device as described in claim 3, characterized in that: A one-way valve (112) is installed at the end of the gas storage chamber (304).

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