Patent Application
20240418687
The invention relates to a gas chromatography instrument, method and computer program for autonomously determining a concentration of a volatile marker in a liquid sample.
A gas chromatography instrument is a well-known instrument for detecting and determining the concentration of gas compounds. It consists of a chromatographic column that has the ability to separate a mixture of gasses into individual components, and a detector that outputs a signal depending on the concentration and/or type of gas that passes through it.
From the prior art, chromatographic instruments are known that allow for a continuous or semi-continuous monitoring of a gas sample utilizing a so-called sample loop. However, sample loops allow for an analysis of gas samples, only. Hence, for applications in which a continuous or semi-continuous monitoring of liquids is required, such devices cannot be used in a satisfactory way. Other devices known from the prior art allow for an analysis of liquid samples, but require providing single liquid doses manually, not autonomously. Such devices are known from U.S. Pat. No. 9,435,772 B2 and EP 2 924 429 A1.
It is an object of the present invention to provide a gas chromatography instrument, method and computer program for autonomously determining a concentration of a volatile marker in a liquid sample.
In a first aspect, a gas chromatography instrument for autonomously determining a concentration of a volatile marker in a liquid sample is presented, the instrument comprising a sampling device configured for autonomously sampling a liquid to be analyzed, a gas sensor, and a conversion device connected to the sampling device and the gas sensor, wherein the conversion device is configured to autonomously convert the sampled liquid into a gas to be analyzed by the gas sensor.
It has been found that by automatically and continuously sampling a liquid to be analyzed and then convert the liquid into a gas that can be analyzed by a gas sensor, multiple types of gas sensors are available that have superior performance in terms of re-usability, reliability and affordability compared to liquid sensors known from the prior art to analyze liquid samples.
The term autonomously is to be understood within this application as continuous or semi-continuous operation, without requiring manual activities from a human operator in the stages between the liquid sampling input stage and sensor output stage. A semi-continuous operation may be conducted, for example, at least hourly.
The proposed gas chromatography instrument may be utilized in agricultural settings for monitoring relevant substances in the substrate or soil water of plants, cow milk or urine collected in the floor of a barn. Another field of application is human healthcare at which relevant biomarkers may be monitored such as creatinine, glucose and cortisol levels from a patient's bloodline or urinary catheter at the hospital bedside or at home.
In a preferred embodiment, the sampling device is connected to a fluid sampling inlet and to a fluid sampling outlet, wherein fluid to be analyzed is provided by the fluid sampling inlet continuously or semi-continuously. The gas sensor preferentially comprises a chromatographic column connected to a detector. In this way, conventional chromatographic columns and detectors having superior performance in terms of re-usability, reliability and affordability can be utilized.
Alternatively, the gas sensor comprises a detector, wherein the detector comprises multiple non-identical sensors. In this embodiment, it is not required to provide a chromatographic column. Instead, the function of the chromatographic column is provided by the detector comprising the multiple non-identical sensors. In particular, an array of sensors may be utilized. The sensors may detect gases based on known techniques like chemoresistive, electro-chemical and optical absorption. The embodiment provides the benefit of a higher measurement speed compared to a solution comprising a chromatographic column and a detector. Preferably, the multiple non-identical sensors comprise different sensor materials and/or operating conditions.
According to one embodiment, the conversion device comprises a droplet dispenser connected to the sampling device, and a pyrolysis well that is configured to convert droplets provided by the droplet dispenser into gas, in particular, by means of heating. The pyrolysis well can beneficially convert non-volatile metabolites into multiple volatile fragments that can be detected with gas chromatography. Preferably, the carrier gas provided to the pyrolysis well does not contain oxygen to avoid a complete conversion to CO2. The pyrolysis in the pyrolysis well can be performed by rapidly heating the wall of the pyrolysis well, either resistively or by means of RF coil, in particular utilizing the curie effect. The droplet can be transported by pressure. e.g. piezo, gravity or electrowetting. Furthermore, the pyrolysis well may utilize split/splitless injection of liquids, heated in the well above their boiling points. For the pyrolysis, the temperature can be lower than the boiling point, since the rapid heating in absence of oxygen breaks molecules into volatile fragments. Preferably, the fragmentation may depend on temperature, which allows for the optional benefit to achieve extra selectivity of marker detection, by performing sequential analysis runs at different pyrolysis temperatures.
According to one embodiment, the sampling device comprises a liquid filter connected to the fluid inlet, wherein the liquid filter provides a retentate stream and a permeate stream, and wherein either of the retentate stream or the permeate stream is connected to the conversion device, in particular the droplet dispenser. The additional liquid filter enhances selectivity for sample liquids containing mixtures of markers. According to an alternative embodiment, the liquid filter may be configured as a liquid chromatography column, to which sample fluid is injected. The output of the liquid chromatography column is fed to the droplet dispenser or any alternative liquid-to-gas converter. For this embodiment, it is beneficial to repeat the liquid-to-gas conversion multiple times, since at different times different compounds will reach the output of the liquid chromatography column.
According to one embodiment, the conversion device comprises a liquid-to-gas-converter that is configured to convert liquid sampled by the sampling device into gas, and a valve arrangement, wherein the valve arrangement is configured to provide the following modes of operation: a feeding mode in which the sampling device is connected to the liquid-to-gas-converter to fill the liquid-to-gas-converter with the liquid sample, a flushing mode in which a carrier gas source is connected to the liquid-to-gas-converter for flushing excess fluid using carrier gas, and an analysis mode in which the liquid-to-gas-converter is connected to the gas sensor. The liquid-to-gas-converter can be configured as a pyrolysis well or a solid-phase microextraction device (SPME).
The conversion device may comprise a six-port-valve connected to the sampling device, the carrier gas source and the gas sensor.
The gas chromatography instrument may further comprise a valve arranged between the liquid-to-gas-converter and the gas sensor, wherein the valve comprises at least three ports, and wherein a first port is connected to the liquid-to-gas-converter, a second port is connected to the gas sensor and a third port is connected to an outlet. In one embodiment, the liquid-to-gas-converter comprises a six-port-valve. In this embodiment, the advantage of a high robustness is achieved, since possible non-volatile ashes that may remain in the pyrolysis well are flushed away in the next sampling phase. Preferably, the surface area next to the pyrolysis well is covered with hydrophobic coating to facilitate the flushing step. In an embodiment, where the solid-phase microextraction device (SPME) is utilized, the SPME is preferably heated gradually or stepwise to achieve desorption of selective volatile species to facilitate selective detection. Preferably, ambient air is used as carrier gas. Due to the SPME sampling, analytes are upconcentrated, resulting in high sensitivity of detection.
In one embodiment, the conversion device comprises a membrane connected to the sampling device and the gas sensor, wherein the membrane is configured to outgas volatile compounds from the liquid sample. This outgassing is also called pervaporation. Preferably, the conversion device comprises three-way valves to allow closing a gas chamber below the membrane to up-concentrate volatile compounds and collectively inject them into the gas sensor. The liquid above the membrane can be heated to enhance the outgassing rate, allowing detection of less volatile compounds. The embodiment takes advantage of a simple construction. Preferably, the membrane is connected to a carrier gas source, wherein ambient air is provided as carrier gas. It is preferred to use a volatile organic compounds (VOC) filter, to filter the ambient air before providing it to the conversion device. The VOC filter removes VOCs present in the sampled ambient air as clean reference. This approach is beneficial compared to carrier gas from a pressurized cylinder, because the embodiment allows having extra underpressure in a gas chamber below the membrane. In one embodiment, the chromatography instrument comprises a processor, wherein the processor is configured to carry out the steps of the method as defined in claim 15.
In another aspect of the present invention, a method for autonomously determining a concentration of a volatile marker in a liquid sample using gas chromatography is presented. The method comprises autonomously providing a sample fluid to be analyzed, autonomously converting at least part of the sample fluid into a gas sample, and autonomously determining a marker concentration in the gas sample.
In a further aspect of the present invention, a computer program for autonomously determining a concentration of a marker in a sample is presented, the computer program comprising program code means for causing an instrument as defined in any of claims 1 to 13 to carry out the steps of the method as defined in claim 14, when the computer program is run on a computer controlling the instrument.
It shall be understood that the gas chromatography instrument of claim 1, the method of claim 14, and the computer program of claim 15, have similar and/or identical preferred embodiments, in particular, as defined in the dependent claims.
It shall be understood that a preferred embodiment of the present invention can also be any combination of the dependent claims or above embodiments with the respective independent claim.
These and other aspects of the invention will be apparent from and elucidated with reference to the embodiments described hereinafter.
In the following drawings:
In the embodiment of
The gas comprising the volatile markers that is generated in the pyrolysis well 28 is provided to the chromatographic column along with carrier gas supplied by the carrier gas source 10. The detector 24 records the output of the chromatographic column 22 as a function of time to establish a chromatogram. To improve a selectivity, different temperatures may be used at the pyrolysis well 28 and the measurement process may be conducted repeatedly for different temperatures. It is preferred that the carrier gas source 10 does not contain oxygen to avoid complete conversion to CO2. The pyrolysis well 28 may comprise a wall that can be heated rapidly, wherein the heating may be conducted by means of an RF coil or resistively. Within the droplet dispenser 26, the droplets can be transported by pressure, for example using the piezo-effect, gravity or electrowetting. In the presented embodiment, the pyrolysis well 28 includes the widely used split/splitless injection of liquids, heated in the well above their boiling points. For the pyrolysis, the temperature can be lower than the boiling point, since the rapid heating in absence of oxygen breaks molecules into volatile fragments.
During feeding mode operation, the pyrolysis well 28 is filled with the sample liquid, when the six-port-valve 32 is in the dotted position. Afterwards, in the flushing mode, the excess fluid is flushed dry using carrier gas provided by the carrier gas source 10 and vented via the outlet 42. Therefore, the six-port-valve 32 is switched into the position illustrated with the dashed black line. Afterwards, in the analysis mode, the pyrolysis well 28 is heated. The resulting volatile pyrolysis products are transported with the help of the carrier gas to the gas sensor 14. Optionally, a surface area next to the pyrolysis well 28 is covered with hydrophobic coating to facilitate the flushing step. This embodiment has been found to be robust, since the possible non-volatile ashes remaining in the pyrolysis well 28 are flushed away in the next sampling phase.
In the embodiment of
In the embodiment of
Solid-phase microextraction (SPME) sorbents are used to extract analytes from the sampled liquid when the six-port-valve 32 is switched to the dotted position. Afterwards, the SPME 62 sorbents are flushed dry using carrier gas in the dashed position of the six-port-valve 32. Excess fluid is vented via the outlet 42. After the SPME 62 is flushed dry, it is heated and resulting desorbed VOCs are transported to and analyzed by the gas sensor 14. The SPME 62 may be heated gradually or stepwise to achieve desorption of selective volatile species to facilitate selective detection. The embodiment of
Other variations to the disclosed embodiments can be understood and effected by those skilled in the art in practicing the claimed invention, from a study of the drawings, the disclosure, and the appended claims.
In the claims, the word “comprising” does not exclude other elements or steps, and the indefinite article “a” or “an” does not exclude a plurality.
A single unit or device may fulfill the functions of several items recited in the claims. The mere fact that certain measures are recited in mutually different dependent claims does not indicate that a combination of these measures cannot be used to advantage.
A computer program may be stored/distributed on a suitable medium, such as an optical storage medium or a solid-state medium, supplied together with or as part of other hardware, but may also be distributed in other forms, such as via the Internet or other wired or wireless telecommunication systems.
Any reference signs in the claims should not be construed as limiting the scope.
The invention relates to a gas chromatography instrument for autonomously determining a concentration of a volatile marker in a liquid sample. The instrument comprises a sampling device configured for autonomously sampling a liquid to be analyzed, a gas sensor, and a conversion device connected to the sampling device and the gas sensor. By utilizing a conversion device that is configured to autonomously convert the sampled liquid into a gas to be analyzed by the gas sensor, an automated continuous monitoring of relevant markers in liquid samples is achieved.
| Number | Date | Country | Kind |
|---|---|---|---|
| 21204430.9 | Oct 2021 | EP | regional |
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/EP2022/078774 | 10/17/2022 | WO |
