CN117309541A

CN117309541A - Sample preparation system and method for extracting analytes from sample by using same

Info

Publication number: CN117309541A
Application number: CN202210680036.3A
Authority: CN
Inventors: 陈晨; 赵永新; 吴升海; 陆段军
Original assignee: Thermo Fisher Scientific Shanghai Instruments Co Ltd
Current assignee: Thermo Fisher Scientific Shanghai Instruments Co Ltd
Priority date: 2022-06-16
Filing date: 2022-06-16
Publication date: 2023-12-29

Abstract

The invention provides a method for extracting an analyte from a sample by a sample preparation system comprising an extraction module, the method comprising the following sequential steps: a) Supplying gas to the sample cell with the sample placed therein to raise the interior of the sample cell to a first preset pressure; b) Supplying a liquid solvent capable of dissolving an analyte in a sample to a sample cell to a first preset amount; c) Supplying a mixture of gas and liquid solvent to the sample cell; heating of the sample cell is started before step b. By pre-filling the gas before supplying the gas-liquid mixture to the sample cell and separately supplying the liquid solvent, the sample recovery and extraction efficiency can be significantly improved. In addition, the invention also provides a sample preparation system.

Description

Sample preparation system and method for extracting analytes from sample by using same

Technical Field

The present invention relates to a sample preparation system, for example, involving solvent extraction techniques. The invention also relates to a method for extracting an analyte from a sample by means of a sample preparation system.

Background

In modern analytical chemistry, there is a need to analyze large amounts of samples, in particular in an automated manner. For this purpose, the target chemical substance (also called analyte) must first be extracted from the sample before it can be measured by analytical techniques.

The method for extracting the sample comprises Soxhlet extraction, ultrasonic extraction, microwave extraction, and accelerated solvent extraction. The concept of accelerated solvent extraction, also known as pressurized solvent extraction, pressurized fluid extraction or enhanced solvent extraction, was proposed in 1995. Accelerated solvent extraction may be used to replace more conventional Soxhlet extraction, sonication, boiling, wrist-type oscillators, and other extraction methods. Accelerated solvent extraction is the extraction of solid and colloidal materials by utilizing the special physicochemical properties of solvents at certain temperatures and pressures. The method has the characteristics of high speed, less solvent consumption, good repeatability and the like. The davan company developed it and commercialized the technology and filed its own instrumentation for a number of U.S. patents, such as U.S. patent nos. 5,647,976, 5,843,311, 5,785,856, etc.

In particular, for example, in solid-liquid extraction techniques, a solid sample may be treated with a liquid solvent to dissolve the analyte in the solvent. Such solid samples may typically be placed within a sample cell of a sample preparation system. Thus, it is necessary to flow a liquid solvent into a sample cell containing a solid sample so that the sample is immersed in the liquid solvent. When the liquid solvent contains the analyte dissolved from the sample, the liquid solvent may be allowed to leave the sample, further concentrated, and then quantified using a suitable analytical technique. Examples of analytical techniques may be, for example, liquid chromatographs coupled to detectors such as conductivity detectors, charge detectors, ultraviolet-visible light spectrometers, or mass spectrometers, and the like. In addition, in order to facilitate subsequent quantitative analysis, it is often necessary to concentrate a large amount of the liquid solvent containing the analyte after extracting the analyte in the sample with the liquid solvent.

Throughout the sample preparation process, it is important to increase the extraction efficiency of the analyte from the sample. In recent decades, the industry has tried to elucidate various factors that affect the extraction efficiency through continuous research, and has actively sought ways to accelerate the extraction kinetics.

For example, to speed up the (e.g., solid-liquid) extraction process, it is known in the art to increase the solubility of the analyte and its diffusion rate in the solvent by heating the liquid solvent itself. However, the temperature cannot be too high in practice, since the analyte may decompose or react with other chemicals in the solid sample. Furthermore, excessive temperatures may cause vaporization of the liquid solvent and significantly impair the extraction performance of the solvent. Thus, there is a limit to the effect of improving the extraction efficiency by the above-described means of the prior art.

In addition, it has been proposed to add gas during solvent extraction to increase the diffusion efficiency of liquid solvents into solid samples and the efficiency of extracting analytes from solid samples. For this purpose, the liquid solvent and the gas need to be combined together to form a mixture before flowing the liquid solvent into the sample cell. After entering the sample cell, the diffusion of this gas phase in the mixture may be several orders of magnitude higher than the liquid solvent phase. Thus, even though the gas itself does not dissolve the analyte, the addition of gas can still improve the overall mass transfer properties of the liquid solvent. In general, gas-assisted solvent extraction techniques not only reduce solvent usage, but it also allows extraction to be performed in a faster time frame. However, there is room for improvement in the gas-assisted solvent extraction technology to further increase the extraction recovery rate and system efficiency.

Furthermore, in order to improve the sample preparation efficiency, a multi-channel extraction method is also adopted. Typically, only one solvent pump is provided in the system, which may lead to problems with uneven solvent flow distribution among the multiple sample cells. In addition, the multi-channel extraction may also produce deviations between sample extraction recovery rates for each channel and also affect the extraction efficiency of the overall system.

For this reason, there is still a constant need in the art to be able to improve the chemical-kinetic equilibrium in the extraction process and thus the overall extraction efficiency of the system.

Disclosure of Invention

In general, the extraction efficiency of extracting analytes from a sample depends on a number of factors, such as pressure, temperature, flow rate, solvent type, and composition of the sample matrix. For example, it is advantageous to maintain a stable extraction pressure within the sample cell, and to select an appropriate extraction temperature. In addition, it is also advantageous to maintain a stable fluid supply flow. The present invention further recognizes that the extraction recovery and extraction efficiency are a combination of the equilibrium relationship between extraction temperature, extraction solvent (or gas-liquid mixture) flow, extraction pressure, such as, but not limited to, whether the sample temperature profile during extraction matches the extent to which the solvent wets the sample, extraction pressure. Especially for multiplex extraction, simply increasing the number of channels, or simply increasing the solvent supply flow, increasing the temperature or increasing the pressure, has limited effectiveness in improving the recovery of the extraction as well as the overall efficiency of the system.

The present invention provides a method of extracting an analyte from a sample by a sample preparation system comprising an extraction module comprising a sample cell for holding a sample containing the analyte, the method may comprise the following sequential steps: a) Supplying gas to the sample cell with the sample placed therein to raise the interior of the sample cell to a first preset pressure; b) Supplying a liquid solvent capable of dissolving an analyte in a sample to a sample cell to a first preset amount; c) Supplying a mixture of gas and liquid solvent to the sample cell; wherein heating of the sample cell is started before step b.

By pre-filling the gas before supplying the gas-liquid mixture to the cell, a high pressure can be reached within the cell, thereby reducing the likelihood of vaporization or boiling of solvent flowing into the cell at higher temperatures. It is further advantageous to bring the sample cell to high pressure rapidly in a short time (e.g., within 5 seconds). This can on the one hand reduce the total length of extraction and on the other hand also allow liquid solvent to enter the sample cell while it is still at a relatively low temperature. By separately supplying the liquid solvent before supplying the gas-liquid mixture to the sample cell, the sample in the sample cell can be infiltrated or wetted by the liquid solvent (for example, more than 70% of the sample is infiltrated by the liquid solvent), thereby avoiding dry burning of the sample due to heating the sample cell before that. Thus, the extraction recovery rate of the sample can be significantly improved.

Advantageously, the extraction module may comprise a plurality of sample cells, wherein step a may comprise supplying gas to each of the plurality of sample cells to raise the interior of each sample cell to a first preset pressure.

By raising each cell to a first preset pressure, non-uniformity between extraction conditions within each cell can be reduced, thereby achieving near extraction recovery and improving overall extraction efficiency.

Also advantageously, the extraction module may comprise a plurality of sample cells, wherein step b may comprise the substep b 1) supplying the liquid solvent to each of the plurality of sample cells in a predetermined sequence; b2 Step b 1) is repeatedly performed so that the liquid solvent supplied to each sample cell reaches a first preset amount.

By supplying the liquid solvent to each of the sample cells in a first predetermined amount, non-uniformity between extraction conditions within each of the sample cells can be reduced, thereby achieving a near extraction recovery and improving overall extraction efficiency. Further, when the liquid solvents are supplied in the same order as predetermined in the respective supply periods, the extraction conditions between the respective sample cells can be further made more uniform, thereby achieving higher uniformity of recovery rates.

Preferably, the extraction module may comprise a plurality of sample cells, wherein step c may comprise the sub-steps of: c1 Supplying the mixture to each of the plurality of sample cells in equal amounts in a predetermined order; c2 Step c 1) is repeatedly executed until a preset stop condition is reached. For example, the preset stop condition may be a first preset time or a second preset amount of the mixture.

When the gas-liquid mixture is supplied in the same predetermined order in each supply cycle, the extraction conditions can be further made uniform between the respective sample cells. The convenient control of the gas-liquid mixture supply can be achieved by a preset time or a preset amount.

In particular, heating of the sample cell may be started before step a. That is, when the sample cell is heated before the supply is started, it is possible to achieve rapid temperature rise of the sample cell and to maintain the temperature within a desired range, and control of the temperature of the sample cell is facilitated.

More preferably, the (supply) flow rate of the liquid solvent into the sample cell in step b may be greater than the (supply) flow rate of the liquid solvent in the mixture into the sample cell in step c. The greater flow rate of the liquid solvent in step b can enable (e.g. more than 70 percent of) samples in the sample cell to be soaked (soaked) with the liquid solvent as early as possible, so that the loss of the samples caused by dry combustion is avoided.

For example, in step c, the mixing ratio of the gas and the liquid solvent may be 1% to 20%, preferably 7.5% to 16%. The gas-liquid mixture with the mixing proportion can achieve better diffusion effect and thus good extraction efficiency.

In some embodiments, the first preset amount in step b may be more than 20% of the sample cell volume, preferably 30% -70%, for example 50%. By correlating the first preset amount with the volume of the sample cell, it is possible to conveniently control the supply amount of the liquid solvent so that the sample is quickly immersed in the liquid solvent before the gas-liquid mixture is supplied. In other embodiments, the first predetermined amount in step b is an amount that provides greater than 70% of the sample in the sample cell to be wetted by the liquid solvent. By correlating the first preset amount with the proportion of the sample immersed in the liquid solvent, the solvent supply amount required for remarkably reducing the possibility of dry burning of the sample in actual conditions can be more similar, so that the expected effect can be achieved with a smaller liquid solvent amount. It will be appreciated that this first preset amount may be learned by calibration before the extraction is started and pre-stored in the controller.

It is contemplated that in step c, a preset flow of gas may be mixed with the liquid solvent to supply the mixed mixture to the sample cell. Because pressure pulsation is generated in the supply line during the process of supplying the fluid, the mixing ratio of the gas and the liquid in the sample cell cannot be precisely controlled. Therefore, by keeping the gas and the liquid solvent mixed at the predetermined flow rate, the decrease in extraction efficiency due to the non-uniformity of the gas-liquid mixture can be reduced.

Further, the first preset pressure may be 200-500psi. The extraction efficiency is improved by supplying gas to the sample cell to achieve a high pressure so that the boiling point of the solvent is raised.

The invention further provides a sample preparation system for extracting an analyte from a sample, comprising: an extraction module, the extraction module comprising: a sample cell for holding a sample containing an analyte; and an extraction heating device for heating the sample cell; a first supply module capable of supplying a gas and a liquid solvent capable of dissolving an analyte in a sample to the sample cell, wherein the first supply module comprises: a first supply line for supplying a gas; a second supply line for supplying a liquid solvent; a first supply control device in fluid communication with the first supply line and having a first operating configuration that allows the first supply line to supply gas to the sample cell and a second operating configuration that prevents the first supply line from supplying gas to the sample cell; a second supply control device in fluid communication with the second supply line and having a first operating configuration that allows the second supply line to supply liquid solvent to the sample cell and a second operating configuration that prevents the second supply line from supplying liquid solvent to the sample cell; a controller configured to: placing the first supply control device in its first operating configuration such that gas flows into the sample cell and placing the second supply control device in its second operating configuration; after the interior of the sample cell is raised to a first preset pressure, placing the first supply control device in its second operating configuration and placing the second supply control device in its first operating configuration, wherein the extraction heating device is controlled to heat the sample cell before the first supply control device and the second supply control device change their operating configurations; and after the first supply module supplies the liquid solvent to the sample cell for a first preset amount, placing the first supply control device in its first operating configuration to supply the mixture of gas and liquid solvent to the sample cell.

By providing the first and second supply control means and the design controller, it is achieved that the gas is pre-filled before the gas-liquid mixture is supplied to the sample cell, whereby a high pressure is reached in the sample cell, thereby reducing the likelihood of evaporation or boiling of the solvent flowing into the sample cell at higher temperatures. It is further advantageous to bring the sample cell to high pressure rapidly in a short time (e.g., within 5 seconds). In addition, the liquid solvent may be separately supplied before the gas-liquid mixture is supplied to the sample cell, so that the sample in the sample cell may be infiltrated with the liquid solvent (for example, 70% or more, preferably 90% or more of the sample is infiltrated with the liquid solvent), thereby avoiding dry heating of the sample due to heating the sample cell before that. Thus, the extraction recovery of the sample can be significantly improved.

Advantageously, the second supply control means may be configured as a solvent pump for pumping the liquid solvent, the solvent pump pumping the liquid solvent to the sample cell in a first operating configuration of the solvent pump, and the solvent pump not pumping the liquid solvent to the sample cell in a second operating configuration of the solvent pump. The switching of the liquid solvent to the sample cell can be simply achieved by controlling the solvent pump so that the liquid solvent or the gas-liquid mixture is supplied to the sample cell for a desired period of time.

Preferably, the extraction module may comprise a plurality of sample cells, the first supply module may comprise a switching valve comprising a first port for inflow of the liquid solvent and a plurality of ports respectively in corresponding communication with the plurality of sample cells, and the controller may be configured to place the first port in fluid communication with one of the plurality of ports for directing the flow of the liquid solvent to one of the plurality of sample cells corresponding to the one of the ports during a corresponding time period of each supply cycle of the liquid solvent or mixture to the sample cells. By means of the switching valve, the liquid solvent (or the liquid solvent part in the gas-liquid mixture) can be guided into the desired sample cells in the desired supply time period, so that the extraction conditions among the sample cells are consistent under the condition of high-flux extraction, and the extraction efficiency is improved.

More preferably, the first supply line may include a plurality of branch lines respectively corresponding to the plurality of sample cells, and the first supply control device may include a plurality of switching devices respectively corresponding to the plurality of branch lines, wherein in a first operating configuration of any of the plurality of switching devices, one of the branch lines respectively corresponding to any of the switches may be in fluid communication with a corresponding one of the plurality of sample cells, and in a second operating configuration of any of the switching devices, one of the branch lines may not be in fluid communication with the corresponding one of the sample cells. By providing a switching device for each gas branch line, the possibility of flowing gas to the desired sample cell can be provided with a simple construction.

In some embodiments, the controller may be configured to, in each supply cycle of gas or mixture to the sample cells, sequentially place each of the plurality of switching devices in its first operating configuration while the remaining switching devices of the plurality of switching devices are in their second operating configuration to sequentially supply gas to each of the plurality of sample cells. Thereby, the gas supply of the respective branch lines to the corresponding sample cell can be simply controlled, so that the gas is guided into the desired sample cell within the desired supply period.

In particular, the first supply module may further comprise a gas source and/or a solvent source. Therefore, the fluid distribution can be realized by comprehensively utilizing and/or solvent sources in the system, for example, the same air source can be adopted to assist in air supply for extraction of the sample cell, vent the evaporation module or purge the sample cell, so that the system efficiency is improved.

In addition, the first supply module may further include a mixing device in which the liquid solvent and the gas are mixed so that the first supply module can supply the mixture to the sample cell.

By supplying the mixed gas-liquid mixture to the sample cell, more uniform diffusion of the gas-liquid mixture in the sample cell can be realized, which is beneficial to improving the extraction efficiency.

Advantageously, in the first supply module, the mixing device may be arranged closer to the sample cell than the switching valve and the switching device. Thus, the mixed gas-liquid mixture can directly flow into the sample cell in the extraction module without passing through other devices, so that the gas-liquid mixture is not uniformly distributed again due to fluctuation. In addition, a plurality of channels corresponding to the switching valve, the gas branch pipeline and the switching device which are positioned at the upstream of the mixing device can be arranged inside the mixing device,

in some embodiments, the first supply module may further comprise a solvent pump for pumping the liquid solvent, the solvent pump being arranged to pump a greater flow rate when the first supply module supplies only the liquid solvent to the sample cell than when the mixture is supplied to the sample cell. By making the flow rate larger when the liquid solvent is supplied alone, the sample (for example, 70% or more) in the sample cell can be immersed in the liquid solvent as soon as possible, avoiding the loss of the sample due to dry burning. At the same time, the flow rate of the liquid solvent is smaller when the gas-liquid mixture is supplied, and better diffusion gradient in the sample cell can be realized.

Drawings

FIG. 1 illustrates a general flow diagram of one embodiment of a sample preparation system according to the present invention; and

FIG. 2 shows a timing diagram of the steps of one embodiment of a method of extracting an analyte from a sample according to the present invention.

List of reference numerals

100. Sample preparation system

110. First supply module

111. First supply pipeline

111a-111e (of the first supply line) first to fifth branch lines

112. Second supply pipeline

112a-112d (of the second or mixed supply line) first to fourth branch lines

113. Solvent pump

114. Gas flow control device

115. Change-over valve

116a-116e first to fifth switching means

117. Mixing device

118. Pressure sensor

122a-122d first through fourth sample cells

124a-124d first through fourth preheaters

130a-130d first to fourth adjusting means

141a-141d first to fourth vaporization containers

142a-142d first through fourth vacuum lines

144. Vacuum valve

145. Vacuum sensor

152. Air source

153. Filter device

154. Solvent source

155. A solvent mixing valve.

Detailed Description

In this context, the sample preparation system and the method of extracting an analyte from a sample by means of the sample preparation system are mainly described with reference to gas-assisted solvent extraction techniques and apparatus therefor, but it will be appreciated that the sample preparation system and the method of extracting an analyte from a sample by means of the sample preparation system of the present invention are not limited to accelerated solvent extraction techniques in the first place, but may also be solid phase extraction techniques (SPE), pressurized fluid extraction (PLE) or other extraction techniques known in the art, and are not limited to application to gas-assisted solvent extraction techniques in the second place. The sample preparation system of the present invention is not limited to the system capable of performing the functions of extraction, evaporation, and the like, and may be a system that performs various functions including the functions of extraction and evaporation, particularly an automated sample preparation system.

In the present invention, the term "sample" refers to a substance that contains a chemical substance to be analyzed (or "analyte") therein when not extracted. The sample is suitable for being placed in the sample preparation system of the invention, in particular in an extraction module thereof. For example, the sample may be loaded into the sample cell of the extraction module if desired, but may also be pre-integrated directly into the sample cell of the extraction module, or may even be placed in the sample cell of the extraction module during the extraction process (e.g., in the case of multiplex extraction). The specific form of the sample is typically a solid phase, but is not precluded from being semi-solid, colloidal, or the like. In addition, the sample may be ground, mixed with a dispersing agent, or may be subjected to other pretreatment prior to being placed in the extraction module, which is not described in detail herein.

In the present invention, the term "analyte" refers to a substance to be analyzed contained in a sample, such as a fatty substance in food, a specific chemical agent in agricultural chemical, or the like. According to the sample preparation principle of the present invention, the analyte contained in the sample can be dissolved out as the liquid solvent flows through the sample, so that the liquid solvent flowing out of the sample cell can contain such analyte for subsequent quantitative or qualitative analysis of the analyte. The liquid solvent for dissolving the analyte in the present invention may contain various types such as n-hexane, DCM (dichloromethane), acetone, etc., and the gas in the present invention may preferably be an inert gas such as nitrogen.

In the present invention, the term "between …" refers to the positioning of a device or component in a flow path. For example, when referring to the conditioning device being arranged between the sample cell and the evaporation vessel, it is meant that the conditioning device is located downstream of the sample cell (i.e. after the sample cell) and upstream of the evaporation vessel (i.e. before the evaporation vessel) as seen in the fluid flow direction.

In the present invention, the term "gas" refers to a gas that does not convert to a supercritical fluid or liquid state within the pressure and temperature ranges described herein. That is, the gas selected in the present invention is a substance that remains in a distinct gas phase under the operating conditions of the extraction process described herein, i.e., the selected gas does not condense into a liquid phase. The gas may be, for example, an inert gas such as helium, neon, argon, or nitrogen, carbon dioxide, air, hydrogen, oxygen, or a combination of the above-described gas types.

In the present invention, when reference is made to supplying a gas, it is generally meant to supply only a gas, and when reference is made to supplying a liquid solvent, it is generally meant to supply only a liquid solvent, unless otherwise specified. If a gas and a liquid solvent are involved, a mixture of a supplied gas and a liquid solvent or simply a gas-liquid mixture will generally be mentioned.

In the present invention, the term "extraction recovery" refers to recovery compared to a standard, for example, a sample obtained by extraction is analyzed by a gas chromatography mass spectrometer (GC-MS) to obtain a ratio of concentration to nominal concentration. The specific calculation process is as follows: a fixed volume of solvent is dispensed with a quantity of standard sample to obtain a standard solvent, which is directly fed into GC-MS for concentration analysis, and a test baseline for recovery can be obtained. The baseline represents 100% recovery assuming no loss of any standard. The same amount of standard is then incorporated into the sample in the sample cell, and during extraction, the standard is solvent extracted and collected into a final concentrated sample, which is finally sent to GC-MS for concentration analysis. If all of the standards can be extracted and left in the final concentrated sample, the analysis should be consistent with the baseline, i.e., recovery can reach 100%. However, sample loss may occur for various reasons, such as insufficient extraction of the standard sample, or volatilization of the standard sample during concentration, resulting in actual recovery rates of less than 100%. Furthermore, the accuracy of GC-MS can also affect the results of the recovery test, for example, causing random errors in the recovery measurement of about 10%. This error can result in the test results for concentrated samples sometimes being higher than the test results for standard solvents, i.e., the calculated recovery can be greater than 100%. In contrast, in the present invention, high extraction efficiency means that as much work (including solvent, temperature, time) as possible is used to achieve as high recovery as possible.

In the present invention, the term "dry combustion" means that the temperature in the sample cell increases to cause a loss of the sample therein. Such loss of sample is undesirable. Such losses may be, but are not limited to, sample vaporization due to temperatures above the boiling point of a portion of the sample, or decomposition of a portion of the sample constituents caused by high temperatures. It will be appreciated that the temperature of the sample cell resulting in dry combustion will vary from sample type to sample type. For example, a lower boiling compound may be used as a sample that is dry burned while the sample cell is still at a lower temperature (e.g., 30-40 degrees celsius).

First, the sample preparation system 100 of the present invention includes an extraction module that may include one or more sample cells into which a sample containing an analyte may be placed. It will be appreciated that the placement of the sample within the sample cell is not a prerequisite for performing the method of extracting the analyte from the sample, that is, the sample may be loaded into the sample cell as desired (one by one or together) during the performance of the method. In some embodiments, when the extraction module includes multiple sample cells, the sample may be loaded into one portion of the sample cells before extraction begins and then reloaded into another portion of the sample cells during extraction.

It should be noted that the terms "cell", "chamber" and "column" are used interchangeably to describe the portion of the extraction module described herein that is used to place a sample, wherein the term "column" (e.g., sample column, packing column, extraction column, etc.) may be used, for example, to describe a sample cell having a cylindrical shape. Alternatively, the sample cell of the present invention may take on a variety of other suitable configurations and shapes. As shown in fig. 1, the sample cell may include an inlet and an outlet. The sample cell should have a substantially closed structure except for an inlet and an outlet for communication with the outside of the sample cell (e.g., a supply line) so that the sample therein does not leak out. Preferably, the inner diameter of the sample cell may be constant.

In general, the volume (axial or radial dimensions) of the sample cell can vary over a wide range. For chemical analysis applications, for example, the volume of the sample cell may range from about 1 to 100mL, such as 1 mL, 10 mL, 33 mL, 66 mL, 100mL, etc., but is not limited to these examples, e.g., may also have a volume greater than 100 mL. Furthermore, the inner diameter of the sample cell may be, for example, 1/16 inch. It is contemplated that the size of the sample cell may be proportional to the sample used. For example, 30g of a soil sample may be used with a 100mL sample cell.

Advantageously, the extraction module of the present invention may comprise one or more extraction channels. In some embodiments, the sample cell may be loaded into the extraction channel (before or during the start of extraction) or pre-fabricated into the extraction channel. In other embodiments, however, the sample cell may not be located within the extraction channel, but rather may be in communication therewith. When the extraction channel is in communication with the sample cell upstream thereof, liquid solvent and gas may flow through the extraction channel before flowing into the sample cell. It should be noted, however, that the extraction channel may also be at least partially located after the sample cell (i.e. downstream of the sample cell) as seen in the flow direction of the fluid, i.e. the fluid flowing out of the sample cell may also flow out of the extraction module via the extraction channel portion located after the sample cell. However, whether the sample cell is located inside, before or after the extraction channel, the sample cell is always in fluid communication with the extraction channel when the extraction module of the present invention includes an extraction channel.

In order to increase the extraction efficiency, the sample temperature in the sample cell may be maintained at a suitable extraction temperature, for example, around 40-200 degrees celsius. Advantageously, the invention may include the step of heating the sample cell to raise (or maintain as required after raising) the temperature of the sample cell (extraction temperature). In the present invention, the sample cell is heated (as will be described in further detail below) prior to extracting the analyte from the sample in the sample cell (or collecting the analyte from the sample).

Preferably, the sample preparation system 100, e.g. the extraction module, of the present invention may comprise an extraction heating device or similar temperature control device. The extraction heating means may comprise an oven or furnace into which the sample cell may be loaded, for example, prior to the initiation of extraction of the sample. Loading the cuvette into the oven may be done automatically by a robot or gripper, but may also be done manually by an operator. An extraction heating device, for example in the form of an oven, can rapidly raise the temperature of the sample cell to the target temperature in a short time, and the stability of temperature control is good.

Additionally or alternatively, the extraction heating means may comprise other forms of heating elements, such as heating wires or heating rods. Preferably, the sample cell may be made of stainless steel, titanium, zirconium, and the like. Sample cells made of these materials may facilitate conduction of heat from an external heat source (via the walls of the sample cell) to the sample cell. In addition, a temperature sensor may be provided within the extraction heating apparatus to facilitate detection and control of the temperature provided thereby.

It is furthermore conceivable that the temperature of the liquid solvent flowing into the sample cell is increased by heating at or preferably before the liquid solvent is supplied to the sample cell, which may help to increase the solubility of the analyte in the liquid solvent and its diffusion rate in the liquid solvent. In addition, increasing the temperature (of the solvent flowing into the sample cell and/or the sample cell itself) also reduces or disrupts the molecular interactions (e.g., van der Waals forces or hydrogen bonding) of the analyte with the matrix and reduces the viscosity of the common type of liquid solvent, which also makes the liquid solvent more accessible to the interstices of the porous matrix, increasing the solvent to sample contact area, thereby increasing extraction efficiency.

In general, the liquid solvent from the solvent container is at an ordinary temperature, and a certain heating time is still required for the solvent at the ordinary temperature to enter the sample cell, and the solvent to be entered into the sample cell can be preheated to a set temperature by a preheater in order to improve extraction efficiency. In particular, the set temperature may be at an excess temperature (preferably 10-50 degrees celsius) to compensate for the temperature drop of the solvent in contact with the sample. For example, a preheater for the solvent may be arranged before the sample cells, in particular one before each sample cell, such that the liquid solvent is heated via the preheaters 124a-124d (see fig. 1) before flowing into the sample cells 122a-122d, but this is not essential. The heating temperature of the preheater may be higher than the heating temperature of the sample cell. Furthermore, it is also contemplated that the preheater may not be located immediately adjacent to the sample cell as shown in FIG. 1, but may be located at any suitable location on the second supply line, or other location within the system.

In order to extract analytes from a sample, a liquid solvent required for extraction needs to be supplied to a sample cell of an extraction module so that analytes in the sample can be dissolved into the liquid solvent flowing into the sample cell. As described above, although the solvent used for extraction is mainly a liquid solvent, a gas-liquid mixture of a liquid solvent and a gas may flow into the sample cell with the aid of a gas. It is understood that the various supply steps of the present invention may be performed with or without the first supply module 110 as will be described in detail below. In other words, the method steps of the present invention may or may not be associated with a device, apparatus, or element to be described in detail below.

First, the method according to the invention comprises a sub-step of supplying a mixture of gas and liquid solvent (or simply gas-liquid mixture) to the sample cell to dissolve the analyte in the sample cell into the liquid solvent and thereby extract it from the sample. The mixture of liquid solvent and gas can increase convection and diffusion mass transfer efficiency in the sample cell, thereby shortening the extraction time, further improving the overall mass transfer property of the liquid solvent and increasing the extraction rate of the analyte.

Advantageously, the temperature of the sample in the sample cell is typically raised to a target temperature prior to extraction to facilitate the increase in the dissolution force of the analyte from the sample into the liquid solvent. But as the temperature increases, the liquid solvent may vaporize and even boil. When the liquid solvent is vaporized or boiled, the amount of liquid solvent available to dissolve the analyte is reduced, resulting in a significant reduction in extraction efficiency.

To this end, the invention further comprises a sub-step of supplying (only) gas to the sample cell before supplying the mixture of gas and liquid solvent to the sample cell. When the sample cell is not in fluid communication with a device downstream thereof, such as an evaporation vessel, the supply of gas to the sample cell can cause the pressure within the sample cell to rise rapidly, thereby effectively raising the boiling point of the liquid solvent and avoiding vaporization of the liquid solvent within the sample cell. If the liquid solvent is vaporized, the sample cell may actually not reach the desired extraction conditions (extraction is only achieved when the liquid solvent is in the liquid state), or it may take more liquid solvent to achieve the same extraction recovery.

As previously mentioned, a high temperature may facilitate dissolution of the analyte from the solid sample into the liquid solvent, while a high pressure may reduce the likelihood of boiling or vaporization of the liquid solvent (at higher temperatures) and thus maintain and enhance the solvating power of the liquid solvent, so that it is advantageous that a particular combination of pressure and temperature may be selected to achieve excellent extraction efficiency when extraction is performed.

It will be appreciated that the present invention supplies gas to the cell as it is supplied (only) until the interior of the cell is raised to a first preset pressure. The first predetermined pressure is, for example, 200-500psi, in particular 220psi, 300psi, 350psi. Here, the term "(supply of gas) until" means that the supply of (only) gas to the sample cell is stopped when the interior of the sample cell is raised to the first preset pressure. In order to avoid erroneous stopping of the gas supply due to pressure fluctuations, the present invention does not exclude stopping of the gas supply when the gas is supplied such that the internal pressure of the sample cell rises slightly above the first preset pressure. It will be appreciated that if the internal pressure of the cell is in turn, for a short time (e.g. a few seconds) after stopping the gas supply, in fact somewhat lower than the first preset pressure for various reasons, it is also possible to not re-supply the cell with (only) gas, but to perform other steps as will be described below or the above sub-steps of supplying a gas-liquid mixture, since such actual errors do not in general affect the achievement of the aforesaid technical effects of the invention.

It should be noted, however, that there are a number of ways in which the determination of whether the first preset pressure is reached (raised) within the sample cell may be made, and even the user of the system of the present invention may not need to make a determination or judgment. In some embodiments, one or more pressure sensors 118 are provided within the extraction module to monitor the pressure within the sample cell or at a point approximately corresponding to the pressure within the sample cell (e.g., a pressure at a location upstream of the inlet of the sample cell). The pressure value monitored by pressure sensor 118 can determine whether the pressure within the sample cell has risen to a first preset pressure. In other embodiments, the gas may be supplied (preferably continuously) to the sample cell for a predetermined period of time (e.g., 5-10 seconds). Preferably, before starting the operation (e.g. calibration during a previous test or extraction), a correlation is made between the time of gas supply and the rise to the first preset pressure, so that the interior of the sample cell can be raised to the first preset pressure by supplying gas for a predetermined time. In other words, by a (calibrated) supply of gas for a predetermined time, it is generally considered that the internal pressure of the sample cell can be raised to a first preset pressure. In this embodiment, the pressure inside the sample cell does not need to be monitored, so that the control operation is convenient, and the number of system components is reduced.

As previously mentioned, in order to raise or maintain the temperature of the sample cell to or at the target temperature (e.g., 40-200 degrees celsius) during extraction, it is preferable to heat the sample cell (initially) in advance. That is, the sample cell is typically already at or near its target temperature before the gas-liquid mixture flows into the sample cell. Especially when the target temperature is set to be high, the sample in the sample cell may be dry-burned for some time because it takes a certain time for the gas-liquid mixture to flow into the sample cell. It should be noted that, instead of dry-burning the sample only when the target extraction temperature is close to high, there is a possibility that the sample will dry-burn even at slightly higher than normal temperature (for example, around 40 degrees celsius). Dry-burn can adversely affect the properties of the sample itself within the sample cell or, more precisely, result in loss of the sample.

To solve this problem, the method of the present invention further comprises, between the two supply sub-steps of supplying gas and supplying gas-liquid mixture, another supply sub-step (also called second supply sub-step) of supplying (only) liquid solvent to the sample cell. It will be appreciated that when the supply of gas to the cell increases to a first predetermined pressure within the cell or for a period of time thereafter (during which no more gas is supplied), the supply of liquid solvent to the cell is initiated until the supply of liquid solvent reaches a first predetermined amount.

In some embodiments, the present invention may control the amount of liquid solvent supplied to the sample cell, i.e., the completion of the supply of the first predetermined amount of liquid solvent indicates that this supply sub-step is complete, and may be turned to other steps. In other embodiments, the present invention may also control the time for supplying (only) liquid solvent to the sample cell. In case the pumping flow of the solvent pump is determined (constant or varying in a predetermined manner), the supply of the liquid solvent for a predetermined time also means that a first preset amount of liquid solvent is supplied. Preferably, before starting the operation (e.g. calibration during a previous test or extraction), a correlation is made between the pumping flow rate of the solvent pump, the supply time and a first preset amount, so that the supply of the first preset amount can be achieved by supplying the liquid solvent for a predetermined time.

In the present invention, it is desirable that the sample in the sample cell is at least partially wetted or wetted with the liquid solvent after the first predetermined amount of liquid solvent is supplied so that the sample cell or the sample therein is not or very little dry burned. Preferably, the first preset amount may be correlated to the volume of the sample cell. In other words, the first preset amount of liquid solvent to be supplied may be set depending on the volume of the sample cell. For example, the first predetermined amount supplied is 30% -70% of the volume of the sample cell, e.g. more than 20%, in particular more than 30%, 40%, 50%. It will be appreciated that different first preset amounts (related to sample cell volumes) may be set for different samples (e.g., differences in porosity). In some embodiments, particularly when the sample cell is a vertically placed column member in the system, it may be determined whether sufficient liquid solvent has been supplied by directly measuring or observing whether the supplied liquid solvent has reached a height above a predetermined percentage of the column member (e.g., above 20% of the volume of the sample cell when the cross-section is constant), without controlling whether the liquid solvent has been supplied by the first preset amount at the supply of liquid solvent.

The method of the invention thus far comprises at least three supply sub-steps performed in succession: 1) Supplying gas to the sample cell with the sample placed therein to raise the interior of the sample cell to a first preset pressure; 2) Supplying a liquid solvent capable of dissolving an analyte in a sample to a sample cell to a first preset amount; and 3) supplying a mixture of gas and the liquid solvent to the sample cell. It will be appreciated that the invention may also include other steps between these supply sub-steps, i.e. between any two consecutive supply sub-steps. Furthermore, there may be time between the beginning of the second supply sub-step and the completion or end of the first supply sub-step (whether there are other steps in between). There may also be time between the start of the third supply sub-step and the completion or end of the second supply sub-step (whether there are other steps in between).

It will be appreciated that it is preferred that the three above sub-steps are performed immediately after each other, i.e. starting to switch to supply (only) liquid solvent to the sample cell once the interior of the sample cell has been raised to a first preset pressure, and switching to supply of the gas-liquid mixture to the sample cell once the supply of liquid solvent has reached a first preset amount. In either case, the present invention includes the three above sequence of steps.

It should be noted that in the present invention, although the solvent extraction is mainly performed with the aid of gas in the third supply sub-step, it is also possible that the analyte in the sample cell is dissolved in the liquid solvent, i.e. the analyte is extracted by the liquid solvent, not only in the third supply sub-step but also in the second supply sub-step.

In the present invention, it is preferable to start heating the sample cell before supplying (only) the liquid solvent to the sample cell. Of course, the sample cell may be heated, for example, to maintain the temperature thereof at the target temperature at all times, at the time of starting or after the supply of the liquid solvent to the sample cell, for example, at the time of supplying the gas-liquid mixture to the sample cell. The foregoing time points are merely illustrative of the time points at which heating of the sample cell is initiated. Advantageously, the target temperature may be a temperature interval, not just a temperature value. Since the liquid solvent is supplied to the sample cell (particularly, a relatively large amount of liquid solvent is supplied in a short time), the sample in the sample cell is already immersed or wetted with the liquid solvent before the supply of the gas-liquid mixture to the sample cell is started, and thus the sample cell is less likely to be dry-burned when heated, particularly, when heated to a relatively high temperature range, and the extraction recovery rate can be significantly improved.

It is particularly preferred that the heating of the cell is started before the (only) gas is supplied to the cell. In other words, the sample cell is heated before starting the whole supply process, for example by loading it into an oven, and then starting the supply sub-steps. Thus, this embodiment is very convenient for system operation and simplified control.

Advantageously, the flow rate of the (only) liquid solvent supplied to the sample cell in the second supply sub-step is larger, in particular much larger, than the flow rate of the liquid solvent in the gas-liquid mixture supplied to the sample cell in the third supply sub-step. For example, the flow rate of the liquid solvent supplied to the sample cell in the second supply sub-step may be on the order of several tens to several hundreds of milliliters per minute (e.g., 30-100 mL/min), while the flow rate of the liquid solvent supplied to the sample cell in the third supply sub-step may be on the order of up to several milliliters per minute (e.g., 0.5-8 mL/min). In the second supply sub-step a higher pumping flow rate is used in order to fill the sample cell with sufficient liquid solvent in a short time (e.g. 10-20 seconds), thereby ensuring that more than 70% of the sample (e.g. more than 80%, 90%, 95% of the sample) in the sample cell is wetted (wetted) by the liquid solvent, thereby reducing the likelihood of the sample being dry burned, as the sample may be wetted by the liquid solvent before being raised to a higher temperature. While in the third supply sub-step, a low solvent flow rate is used to maintain a high diffusion gradient of the analyte in the sample cell, which will greatly increase the extraction efficiency.

To supply a fluid, for example a fluid (liquid solvent, gas or a mixture of both) to a sample cell, a sample preparation system 100 according to the present invention may comprise a first supply module 110. Herein, the term "first supply module" may encompass any device or component that provides a fluid, such as a liquid solvent, a gas, or the like. It is to be understood that the first supply module 110 of the present invention may, but may not, include a solvent source 154 (e.g., a container containing a liquid solvent), a gas source 152 (e.g., a compressed nitrogen cylinder), devices or components directly associated with the solvent source 154 and the gas source 152 (e.g., a gas source switch, a filter 153, a pressure sensor 118, a solvent mixing source 155), and the like. For example, as shown in fig. 1, a solvent mixing valve for mixing between different solvents may also be arranged upstream of the solvent pump 113.

Further, it should also be noted that the first supply module 110 of the present invention is not limited to supplying liquid solvents, gases to an extraction module, but may also be supplied to other modules or devices of the sample preparation system 100 of the present invention (e.g., evaporation modules, etc., as will be described in detail below). In other words, the first supply module 110 of the present invention may utilize at least a portion of its common piping, devices, or elements to supply liquid solvent, gas, or a mixture of both to other modules or devices other than the sample cell, such that the number of overall components of the system is reduced and sample preparation efficiency is optimized.

Referring to fig. 1, the first supply module 110 may include a first supply line 111 for supplying gas. The first supply module 110 may further include a second supply line 112 for supplying the liquid solvent. It will be appreciated that the first supply line 111 and the second supply line 112 do not have to be physically rigidly fixed for supplying gas and liquid solvents, but that at least a part of the lines may be used for supplying both gas and liquid solvents at different stages or points in time of sample preparation, e.g. extraction, e.g. a common line (which may also be referred to as a mixing supply line as the case may be) between the mixing device 117 (described in more detail below) and the sample cell as shown in fig. 1. In other words, for some of the lines in the first supply module 110, there is a flow of gas at some times and a flow of liquid solvent at other times (see in particular further details below). Furthermore, in embodiments of gas-assisted solvent extraction, some of the lines in the first supply module 110 also supply a mixture of gas and liquid solvent, i.e. both gas and liquid solvent flow through these lines at the same time (which may be referred to as mixed supply lines). It should also be appreciated that the first supply module 110 may include other supply lines that are not used to supply liquid solvents or gases.

As previously mentioned, in order to rapidly increase the extraction temperature, the liquid solvent or mixture of gas and liquid solvent may advantageously be preheated to a target temperature (e.g., 40-200 ℃) prior to entering the sample cell. It will be appreciated that the temperature of the preheated liquid solvent may be different from the (extraction) temperature of the sample cell. The means for preheating the liquid solvent (e.g., the preheaters 124a-124d shown in fig. 1) may be of known construction and will not be described in detail herein.

The first supply module 110 may include a first supply control device in fluid communication with the first supply line. For example, the first supply control device may be arranged on the first supply line (i.e. in the flow path of the first supply line). The first supply control means may have a first operating configuration allowing the first supply line 111 to supply gas to the sample cell and a second operating configuration preventing the first supply line 111 from supplying gas to the sample cell. In some embodiments, the first supply control device may be configured as a switching device, such as a switching valve, but may also be another valve with an adjustable opening. When the first supply control device is a switching device, the first operating configuration may for example be an on state of the switching device, and the second operating configuration may for example be an off state of the switching device.

The first supply module 110 may also include a second supply control device in fluid communication with the second supply line. For example, the second supply control device may be disposed on the second supply line 112 (i.e., in the flow path of the second supply line 112). The second supply control means may have a first operating configuration allowing the first supply line 111 to supply gas to the sample cell and a second operating configuration preventing the first supply line 111 from supplying gas to the sample cell. In some embodiments, the second supply control device may be configured as a solvent pump 113 for pumping the liquid solvent. In the first operating configuration, the solvent pump 113 is operated to pump liquid solvent, while in the second operating configuration, the solvent pump 113 is not operated, and therefore typically no liquid solvent is pumped to the extraction module. In other embodiments, the second supply control device may be configured as other devices or components that enable solvent switching.

It will be appreciated that in the first operating configuration of the solvent pump, the possibility that liquid solvent will not be supplied to the sample cell of the extraction module is not precluded, perhaps because the first supply module 110 also includes means for selectively switching the flow path between the solvent pump 113 and the extraction module, such as a diverter valve 115, or other switching means. But in the present invention, if a solvent pump is used as the second supply control means, it means that it may allow or prevent the flow of the liquid solvent therethrough in terms of the solvent pump itself.

Where the first supply module 110 of the present invention includes a gas source, the first supply control device may also be a gas line switch, valve or the like on the gas source. Where the first supply module 110 of the present invention includes a solvent source, the second supply control device may also be a switch, valve or similar device located at the solvent source.

Typically, solvent pump 113 is capable of pumping liquid solvent at a relatively steady flow rate, which may be preset, but which may also be adjusted online by the user. In addition, the first supply module 110 may further have other valves disposed between the solvent pump 113 and the switching valve 115 to flexibly adjust the on-off of the fluid on the second supply line 112 or further adjust the flow rate of the liquid solvent.

It is contemplated that solvent pump 113 may be briefly placed in its second operating configuration during a transition between sample cells via transition valve 115, as will be described in greater detail below, to avoid high pressure due to a blockage of the passage during the transition valve 115. However, it is also possible to maintain the solvent pump 113 in the first operating configuration during this process so that the liquid solvent flowing into the switching valve 115 is uninterrupted.

To supply the sample cell with a mixture of liquid solvent and gas, the first supply module 110 may further comprise a mixing device 117 for mixing the gas with the liquid solvent. In some embodiments, the mixing device 117 is configured as a fluid junction (see fig. 1) that includes separate inlets for allowing liquid solvent and gas, respectively, to enter and outlets for allowing the mixed mixture to exit. In other embodiments, however, the mixing device 117 may take other configurations, such as valves, manifolds, and the like. It will be appreciated that the mixing device 117 of the present invention may also be embodied as a broad sense of mixing means, for example, one mixing line into which the first supply line 111 for supplying gas and the second supply line 112 for supplying liquid solvent may be incorporated, not necessarily a dedicated mixing device. For example, there is no dedicated mixing device, but the portion of the piping where the first supply piping 111 merges or merges with the second supply piping 112 may be referred to as a mixing device.

As shown in fig. 1, in the first supply module 110, the mixing device is advantageously arranged closer to the sample cell of the extraction module than the switching valve and the switching device, i.e. the mixing device is arranged downstream of the switching valve and also downstream of the switching device.

In order to perform the above mentioned supplying step, the present invention may comprise a controller. It will be appreciated that the controller of the present invention may also perform other method steps of the present invention, such as controlling various devices, apparatus to perform predetermined procedures, such as heating, evaporating, bubbling, purging, etc.

Specifically, corresponding to the first supply sub-step, the controller may be configured to place the first supply control device in its first operational configuration (e.g., the switching device is in an on state) such that gas flows into the sample cell, and to place the second supply control device in its second operational configuration (e.g., the solvent pump is not operational) such that liquid solvent does not flow into the sample cell. That is, only gas is supplied to the sample cell to rapidly raise the pressure within the sample cell, thereby reducing the likelihood of vaporization of the subsequently inflowing liquid solvent.

It should be noted here that "having … in the first/second operational configuration" means that the controller ensures that it is in the first or second operational configuration, but it is not necessary that the controller will signal to perform the action of placing the corresponding supply control device in the corresponding first or second operational configuration, as the corresponding supply control device may already be in the first or second operational configuration before starting the method of the invention.

After the pressure inside the sample cell has risen to the aforementioned first preset pressure, the controller may place the first supply control means in its second operating configuration so that no gas is supplied to the sample cell anymore, and place the second supply control means in its first operating configuration so that liquid solvent is supplied to the sample cell. It will be appreciated that the controller may begin the above operation immediately upon the pressure within the sample cell reaching (rising to) the aforementioned first preset pressure, but may begin the above operation after waiting for some time, and the present invention does not exclude other operations being performed by the controller during this time.

Preferably, the controller is further configured to heat the sample cell before the first supply control means and the second supply control means change their operating configurations as described above (i.e. the first supply control means changes from the first operating configuration to the second operating configuration and the second supply control means changes from the second operating configuration to the first operating configuration), for example by means of the aforementioned extraction heating means. The controller controls the heating of the sample cell at least before the first and second supply control means change their operating configurations as above, for example the heating process may be started when the first supply control means is in its first operating configuration and the second supply control means is in its second operating configuration, or the heating process may be started before the supply step of the invention is started (no matter what operating configuration the first and second supply control means are in). In the present invention, the controller may control not only heating the sample cell to the target temperature but also heating the sample cell for a desired time.

Advantageously, the solvent pump of the present invention may be further configured such that the pumping flow rate (e.g., on the order of tens of milliliters/minute) when the first supply module 110 supplies only liquid solvent to the sample cell is greater than the pumping flow rate (e.g., on the order of a few milliliters/minute) when the mixture is supplied to the sample cell.

After the first supply module 110 supplies the liquid solvent to the sample cell by a first predetermined amount, the controller may be further configured to place the first supply control device in its first operational configuration to re-supply the gas to the sample cell, i.e., at which point the first supply module 110 supplies the mixture of gas and liquid solvent to the sample cell, because the controller does not change the operational configuration of the second supply control device at which point (i.e., it is still in the first operational configuration to supply liquid solvent to the sample cell).

When the analyte is dissolved in the liquid solvent, the liquid solvent containing the analyte may flow out of the sample cell of the extraction module (e.g., via an outlet of the sample cell) for subsequent operation (as will be further explained below). It will be appreciated that other fluids, such as gases, if any, may also flow from the sample cell during this process. To collect the liquid solvent containing the analyte, the sample preparation system 100 of the present invention may include a collection container.

Alternatively or additionally, the sample preparation system 100 of the present invention may comprise an evaporation module. The evaporation module may include an evaporation vessel (e.g., 141a-141 d), such as an evaporation bottle, for receiving the liquid solvent flowing from the sample cell. The liquid solvent containing the analyte may be evaporated in the evaporation vessel, i.e. the liquid solvent containing the analyte in the evaporation vessel is evaporated. It will be appreciated that the system of the invention may also not comprise an evaporation module, but rather a collection vessel for collecting liquid solvent containing the analyte from the sample cell is provided just downstream of the extraction module.

In the present invention, the term "evaporation" refers to a physical process of concentrating the volume of a liquid substance (i.e., a liquid solvent) by vaporizing it. The evaporation process of the evaporation module may be performed by means including, but not limited to, heating, depressurizing (e.g., evacuating), blowing (e.g., nitrogen blowing), any combination thereof, or the like. It will be appreciated that in the present invention, the analyte dissolved in the liquid solvent should generally not or only very little vaporise by evaporation. Thus, as the liquid solvent containing the analyte is evaporated by means of the evaporation module, a large amount of the liquid solvent may be allowed to evaporate, thereby obtaining a desired volume of the liquid solvent containing the analyte (also referred to as "concentration") for subsequent quantitative analysis of the analyte.

Preferably, the extraction module may be in selective fluid communication with the evaporation module. Specifically, the sample cells (e.g., 122a-122 d) of the extraction module may be in selective fluid communication with the evaporation vessels (e.g., 141a-141 d) of the evaporation module. In some embodiments, the extraction module may include a plurality of sample cells, and the evaporation module may include a plurality of evaporation vessels. As shown in fig. 1, each of the plurality of sample wells may be in selective fluid communication with a corresponding one of the plurality of evaporation vessels, i.e., in a one-to-one correspondence.

In addition to the evaporation vessel, the evaporation module may further comprise one or more means for facilitating evaporation of the liquid solvent, for example evaporation heating means for heating the evaporation vessel, to achieve a controlled evaporation process by increasing the temperature. If the evaporation module comprises a plurality of evaporation vessels, these can all be arranged in one temperature control device, but it is also possible to provide each evaporation vessel with separate evaporation heating means or elements, such as heating wires, heating rods, heating cartridges, etc.

For another example, the evaporation module may further include a suction (vacuuming) device for decompressing the inside of the evaporation container so that the evaporation area increases or the liquid level pressure decreases, accelerating the vaporization of the liquid solvent in the evaporation container. In this case, the evaporation module comprises suction lines or vacuum lines which open into the evaporation vessel and which communicate with suction devices (e.g. vacuum pumps, vacuum generators, etc.) located outside the evaporation vessel. The evaporation module may also be provided with a pressure sensor or vacuum sensor 145 on the suction line or vacuum line or within the evaporation vessel to monitor the vacuum level in the evaporation vessel in real time.

The evaporation module may further comprise a blowing or air-blowing device in order to accelerate the evaporation process of the solvent. The blowing or bubbling device is configured to blow or bubble a gas, such as an inert gas, through a conduit into the liquid solvent in the vaporization vessel such that the surface area of the liquid solvent increases, thereby significantly increasing the vaporization rate under the same conditions (same temperature, vessel cross-sectional area, etc., factors affecting vaporization). As previously mentioned, in addition to supplying the sample cell, the first supply module 110 of the present invention may also utilize at least part of its common piping, devices or elements to supply a gas, such as nitrogen for nitrogen blowing, to the evaporation module, primarily its evaporation vessel. Thus, a separate gas source 152 and part of the gas lines for evaporation can be saved.

During extraction, especially during gas-assisted solvent extraction, it is desirable to keep the pressure in the sample cell as stable as possible. As previously mentioned, the liquid solvent needs to remain in its liquid phase in the sample cell, otherwise the efficiency of solvent extraction will be significantly reduced. When the pressure in the sample cell can be kept at a higher preset pressure, it can be ensured that the liquid solvent is not vaporized in the sample cell.

In order that higher pressures may be established within the sample cell, it is preferred that the sample preparation system 100 of the present invention may include a conditioning device. The adjusting means may be arranged downstream of the extraction module, for example in communication with the outlet of the sample cell. When the system of the invention comprises an evaporation module, the adjusting means may be arranged between the extraction module and the evaporation module, in particular on the flow path between the sample cell and the evaporation vessel. More precisely, the regulating device may be in fluid communication with the sample cell and the evaporation vessel, respectively. Thus, in some embodiments, selective fluid communication between the sample cell and the evaporation vessel may be achieved by means of the adjustment means. Advantageously, the adjustment means may be driven by actuation means, for example a stepper motor.

The regulating device of the present invention has an inlet and an outlet. In some embodiments, the inlet may be in communication with the sample cell and the outlet may be in communication with the evaporation vessel, with the flow path between the inlet and the outlet being formed inside the conditioning device. A fluid (e.g., a liquid solvent, a gas, or a mixture of both) can flow from an inlet to an outlet via a flow path internal to the conditioning device. In the present invention, the cross-sectional size (or expressed by a relative value of dimensions) of the portion of the flow path of which the cross-section is changeable from the inlet to the outlet is referred to as the "opening degree" of the regulating device. For example, when the cross-sectional dimension is a variable maximum, it may be referred to as an opening maximum, and when the cross-sectional dimension is zero (i.e., the flow path is non-conductive), it may be referred to as an opening minimum. The opening degree of the adjusting means may be varied between a maximum opening degree (100% opening degree) and a minimum opening degree (0 opening degree). When the pressure in the sample cell is relatively stable, the opening of the regulating device may be stabilized near a certain equilibrium position, which may be between a maximum opening and a minimum opening.

The adjustment device may have an operating mode and a non-operating mode. In the non-operating mode of the regulating device, the opening of the regulating device is at a maximum, so that fluid communication can be established between the sample cell and the downstream collection or evaporation vessel. This mode is for the fluid to pass through the sample cell at a maximum flow rate quickly, for example when a purge gas is supplied to the sample cell for purging. In the operating mode of the adjusting device, the opening degree of the adjusting device is changeable. In particular, the regulating device may regulate its opening based on the pressure in the sample cell, and then by means of such a variation of the opening the pressure in the sample cell may be maintained within a preset interval.

In particular, when the pressure in the sample cell is relatively stable, the opening of the regulating device is also substantially stable in its equilibrium position. When there is a fluctuation in the pressure in the sample cell, for example, when the pressure in the sample cell suddenly increases, the pressure at the inlet of the regulating means also becomes large due to the sample cell communication, and such a large pressure causes the opening degree of the regulating means to become large, and the opening degree of the regulating means becomes large so that the resistance that can flow through the regulating means becomes small, i.e., the flow-through amount becomes large, which can cause the pressure (resistance) of the flow path to become small, and thus the pressure in the sample cell to decrease, thereby balancing the aforementioned sudden pressure fluctuation. Conversely, if the pressure in the sample cell suddenly decreases, the opening degree of the regulator becomes smaller, which increases the pressure (resistance) of the flow path, and thus increases the pressure in the sample cell again.

Thus, the conditioning apparatus of the present invention can provide a negative feedback to pressure fluctuations within the sample cell (e.g., 122a-122 d) to return to its steady pressure as soon as possible. In other words, even if there is fluctuation in the pressure in the sample cell, the pressure can be made to float up and down in a small section around a certain pressure value without exceeding the preset section due to such a negative feedback mechanism, thereby achieving desired pressure stability. Therefore, in the operation mode of the regulating device, the regulating device not only can allow the flow path between the sample cell and the evaporation container to be conducted or cut off, but also can be used for stabilizing the pressure in the sample cell in a smaller preset interval. It is particularly advantageous that the regulating device can keep the pressure in the sample cell within a range of 1%, 2%, 3%, 5% of a preset pressure, in particular a higher pressure (e.g. 200-500psi, in particular 220-300 psi) floating up and down.

According to the invention, in an embodiment provided with such a regulating device, in the first supply sub-step, when gas is supplied to the sample cell, the pressure has not yet reached a pressure value which enables the flow path inside the regulating device to be conducted due to the presence of the regulating device in the operating mode, and thus the regulating device now places the sample cell in fluid communication with downstream devices, such as evaporation vessels (i.e. the regulating device provides a back pressure), and thus the pressure inside the sample cell can rise rapidly due to the supply of gas. In the third supply sub-step, the pressure inside the sample cell can be kept always within a preset pressure interval (e.g., 220psi, 300 psi) by means of the regulating device when the gas-liquid mixture is supplied to the sample cell.

In gas-assisted solvent extraction techniques, a mixture of liquid solvent and gas is supplied to the sample cell (e.g., 122a-122 d) due to the need. The gas-liquid mixing ratio of the two can advantageously be controlled, in particular continuously. To this end, the supplying step of the method of the present invention may comprise supplying a predetermined flow rate of gas to the sample cell to be mixed with the liquid solvent during the supplying of the mixture of gas and liquid solvent. Preferably, the first supply module 110 of the sample preparation system 100 may comprise a gas flow control device 114 by means of which gas flow control device 114 a preset flow (e.g. 1-200 ml/min) of gas is to be supplied for mixing with the liquid solvent during the supply of the mixture of gas and liquid solvent. Of course, the invention may also be implemented by other means.

The gas flow control device 114 may be disposed on the first supply line 111 or may be in fluid communication with the first supply line 111. The gas flow control device 114 may include an inlet and an outlet, the inlet of which may be in communication with the gas source 152 and the outlet of which may be in communication with the extraction module. Typically, the inlet pressure of the gas flow control device 114 is higher than the outlet pressure. The outlet pressure of the gas flow control device 114 may also be maintained within a steady preset interval (e.g., 220-300 psi) with the adjustment device described above. Since the gas source 152 preferably provides pressurized gas, the inlet pressure of the gas flow control device 114 is generally high, such as 250-400psi, particularly 300-350psi.

The gas flow control device 114 may include a flow control mode in which a constant steady flow of gas may be provided to the sample cell. Since the gas flow remains stable, the gas in the mixture of liquid solvent and gas will also occupy a stable proportion. This may allow for a uniform mixing of the gas in the mixture, i.e. mixing of the gas into the liquid solvent. It will be appreciated that the steady gas flow provided by the gas flow control device 114 of the present invention is itself user-presettable to adjust the desired gas-liquid mixing ratio during gas-assisted solvent extraction to optimize extraction performance.

In addition, the gas flow control device 114 may also include a fully open mode. The fully open mode may be applied to a stage of rapidly increasing the pressure in the sample cell prior to supplying the gas-liquid mixture, for example in the aforementioned first supply sub-step. As previously mentioned, the relatively high pressure within the sample cell is a critical factor in maintaining the liquid solvent in the liquid phase at high temperatures. Increasing the pressure in the sample cell (e.g., to a pressure value between 200-500 psi) eliminates the loss of liquid solvent due to possible vaporization, since such high pressures directly increase the boiling point of most organic solvents, thereby keeping the liquid solvent in the sample cell in the liquid phase. Preferably, rapidly increasing the pressure in the cell, for example within 5 seconds, to the first preset pressure, creates the desired high pressure in the cell before the temperature of the cell increases much (e.g., slightly above ambient temperature), which also helps to subsequently avoid the possibility of dry burning of the sample in the cell.

It will be appreciated that once the desired high pressure is present in the sample cell, the gas flow control device 114 may be transitioned from a fully open mode (automatic or manual) to a flow control mode (e.g., in the aforementioned third supply substep) to facilitate auxiliary operation of the gas, but such transition may be performed automatically or manually under other conditions (e.g., preset times). In some embodiments, the transition from the fully-open mode to the flow control mode (i.e., upon entering the third supply sub-step) may occur when the liquid solvent in the sample cell reaches a first preset amount.

To optimize extraction efficiency, the extraction module of the present invention may include multiple sample cells (e.g., two, four, eight sample cells). Likewise, the evaporation module of the present invention may also comprise a plurality of evaporation vessels (e.g., two, four, eight evaporation vessels). As previously described, each of the plurality of sample cells (e.g., 122a-122 d) may be in selective fluid communication with a corresponding one of the plurality of vaporization containers (e.g., 141a-141 d). Preferably, the sample preparation device of the present invention may further comprise a plurality of adjustment means, one adjustment means being arranged between each sample cell and a corresponding one of the evaporation vessels.

In the present invention, whether performed sequentially or simultaneously, supplying the liquid solvent, gas, or a mixture of both to the plurality of sample cells (e.g., 122a-122 d) may be referred to as multiplexing, dissolving the analyte in the sample in the liquid solvent in the plurality of sample cells may be referred to as multiplexing, and evaporating the liquid solvent containing the analyte in the plurality of evaporation vessels may be referred to as multiplexing. The expression "multiplex" is intended to distinguish between the cases where only a single sample cell is supplied, extraction is performed in a single sample cell, evaporation of the liquid solvent within a single evaporation vessel is performed. By means of the multi-path arrangement, the same device can meet the requirements of different processing capacities of users.

In some embodiments of the invention, the liquid solvent or gas-liquid mixture may be supplied to each of the sample cells sequentially, but in other embodiments the liquid solvent or gas-liquid mixture may be supplied to a plurality of sample cells together. While a greater throughput can be achieved by simultaneously supplying liquid solvent or gas-liquid mixture to each cell, sequentially filling each cell with liquid solvent or gas-liquid mixture (also referred to as batch supply or filling) can be beneficial for faster solvent equilibration and higher extraction recovery. It will be appreciated that the method of the present invention may be switched automatically or manually between supplying liquid solvent or a mixture thereof with gas to each cell simultaneously and sequentially to each cell, thereby increasing the flexibility of operation.

In particular, intermittent delivery of liquid solvent allows for faster equilibration times to predetermined extraction temperatures and more efficient extraction of analytes than continuous solvent flow through each extraction channel or each sample cell. Further, it can be noted that in the case of sequential supply, there is a static extraction time since one sample cell is supplied with liquid solvent while the other sample cells are not supplied with liquid solvent. In the present invention, the term "static extraction time" refers to the time during which the liquid solvent is not supplied to the sample cell. It will be appreciated that the static extraction time does not of course mean that the liquid solvent does not flow through the sample cell into the evaporation vessel, but rather simply means that no liquid solvent is supplied to the sample cell during the static extraction time.

In a preferred embodiment of the multiplex supply, for the first supplying sub-step, it may comprise supplying gas to each of the plurality of sample cells to raise the interior of each sample cell to a first preset pressure. In the present invention, supplying gas sequentially or in a predetermined order once to each of the plurality of sample cells is referred to as one supply period. The first supplying sub-step may include one or more supplying cycles. When the supplied gas pressure is high (e.g., when the gas is from a high pressure gas source), only one supply cycle of gas may be supplied (e.g., see fig. 2), allowing the pressure within each sample cell to rise to a first preset pressure. It is also conceivable that the pressure in each sample cell is raised to the first preset pressure by supplying gas for a plurality of supply cycles.

In a preferred embodiment of the multiplex supply, the second supply sub-step may further comprise two sub-steps in succession: 1) Supplying a liquid solvent to each of the plurality of sample cells in a predetermined sequence; 2) The first substep is repeatedly performed such that the liquid solvent supplied to each of the sample cells reaches a first preset amount. Thus, a first predetermined amount of liquid solvent may be for each sample cell. As previously mentioned, the first preset amount is advantageously related to the volume of each sample cell. Here, the first substep is performed once each time, namely, one supply period in which the liquid solvent is supplied to each of the sample cells, and how many supply periods are performed is related to whether each of the sample cells reaches the first preset amount of the liquid solvent. Preferably, the second supplying sub-step may comprise a plurality of supplying cycles, for example three to five cycles.

In a preferred embodiment of the multiplex supply, the third supply sub-step may further comprise two sub-steps in succession: 1) Supplying the mixture to each of the plurality of sample cells in a predetermined sequence, in particular equally; 2) And repeating the first substep of the steps until a preset stopping condition is reached. For example, the preset stop condition may be a first preset time or a second preset amount of the gas-liquid mixture (i.e., the gas-liquid mixture that has reached the first preset time or been supplied by the second preset amount is stopped, otherwise the supply cycle of the gas-liquid mixture is always performed). In the present invention, the preset stop condition, i.e., stopping the supply of the gas-liquid mixture, is typically achieved because a desired or near-desired amount of analyte has been extracted from the sample cell. Preferably, the second supplying sub-step may comprise a plurality of supplying cycles, for example five to fifteen cycles.

In the present invention, the term "sequential" refers to sequential or in a (e.g., predetermined) order. Advantageously, the predetermined sequence (i.e., the sequence of supplying gas, liquid solvent or gas-liquid mixture to the plurality of sample cells) is maintained constant between different supply periods or supply cycles, as this allows the extraction conditions of the individual sample cells to be kept as consistent as possible, thereby improving recovery.

Furthermore, the term "equivalent" means that the volumes of the supplied gas, liquid solvent, or a gas-liquid mixture of both are the same. This is advantageous for multiplex extraction, as it may further allow the extraction conditions of the individual sample cells to be kept more consistent, resulting in closer extraction recovery between individual sample cells and shorter overall extraction times. In addition, supplying each sample cell in equal amounts in one supply cycle generally means that the duration of the supply is also the same for each sample cell (assuming that the supply flow is substantially the same). This may allow for temperature variations, pressure variations, static extraction times, etc. to be substantially uniform for each cell, so that an optimal overall chemo-dynamic balance may be obtained for a plurality of cells.

In one example, in the case of four extraction channels (i.e., four sample cells), one supply cycle has a duration of 60 seconds, and each cell may preferably be sequentially supplied with 15 seconds of liquid solvent or a mixture of liquid solvent and gas. That is, after one sample cell is supplied with liquid solvent or gas-liquid mixture for 15 seconds, the system will switch to the next sample cell for supply. In this example, three-quarters of the static extraction time per cell occurs during one supply cycle. It will be appreciated that the time to supply each cell may not be the same 15 seconds, for example one cell may supply 10 seconds and another cell may supply 20 seconds, and so on, but this is not preferred.

It should be noted, however, that for convenience of description, it is specified in the present invention that the supply period for not sequentially supplying the gas-liquid mixture (either only the liquid solvent or only the gas) to each of the sample cells does not belong to one of the aforementioned plurality of supply periods, and that the sample cell to which the gas-liquid mixture is not supplied does not belong to one of the aforementioned plurality of sample cells. In other words, the present invention does not exclude that the gas-liquid mixture is not sequentially supplied to each of the sample cells in other supply periods, nor that there are sample cells that are not supplied with the gas-liquid mixture, but that these supply periods do not belong to one of the plurality of supply periods defined previously, and that these sample cells do not belong to one of the plurality of sample cells defined previously.

In the case of a constant supply amount, the use of a plurality of supply periods can better ensure that the extraction conditions between the individual sample cells are more uniform than in the case of an embodiment comprising only one supply period (i.e., a desired total amount of liquid solvent or gas-liquid mixture is supplied to one sample cell and then transferred to the next sample cell). The static extraction time of each cell can also be kept substantially uniform through multiple supply cycles. In addition, by increasing the frequency of switching between individual sample cells (i.e. supplying each sample cell for a short period of time, in particular in the third supply sub-step), the temperature variation differences in the extraction of the individual sample cells or of the individual extraction channels can also be minimized, i.e. the extraction conditions are more uniform, whereby a good thermodynamic equilibrium between the individual sample cells can be maintained. It should also be noted that since the liquid solvent (i.e., in the second supply sub-step) or its gas-liquid mixture (i.e., in the third supply sub-step) is supplied intermittently between the individual sample cells (i.e., there is the aforementioned static extraction time), there are conditions that change the liquid solvent, thereby changing the extraction conditions as needed, providing overall flexibility of the system.

As previously described, the duration or amount of supply of the gas-liquid mixture to each sample cell is equal in the same supply cycle. Due to the design of the same supply time or supply volume, it is possible to ensure that the extraction conditions are consistent between the individual sample cells (e.g. that their physical parameters, such as pressure, temperature, flow etc. remain as consistent as possible for the extraction), and thus a more consistent recovery rate can be obtained and a shorter overall extraction time results. For example, more closely spaced extraction conditions can be achieved by supplying the same amount of gas-liquid mixture in the same segment of the temperature rise profile of the sample in each sample cell.

The invention is not limited in this regard and the duration of the gas-liquid mixture supplied to each cell may vary from cell to cell (e.g., 122a-122 d), or at least in part, but the same time is most preferred. In addition, the amount of mixture or the duration of supply to each of the sample cells may be the same or different in different respective supply cycles, but it is still preferable that the time for supplying the gas-liquid mixture to the respective sample cells in the same supply cycle be the same.

It is also preferable that the total duration of each supply cycle or the supply time or supply amount to each sample cell in each supply cycle in the case of an equal amount of supply be kept small (e.g., 15 seconds) to minimize the adverse factors of the decrease in recovery rate due to the uneven increase in extraction temperature.

In the present invention, the amount of liquid solvent supplied to the (each) sample cell may be adjusted by the user or may be preset. For example. The sample cell may be supplied with a liquid solvent corresponding to 20-80% of its volume, in particular 30-70% of its volume. In some cases, the greater the amount of liquid solvent supplied to the sample cell (e.g., the greater the volume), the better the extraction recovery.

To sequentially supply liquid solvent or a mixture of liquid solvent and gas to the sample cells (e.g., 122a-122 d), the first supply module 110 of the present invention may include a switching valve 115 (e.g., a multi-way rotary valve), the switching valve 115 being in communication with the second supply line 112. The switching valve 115 may have a plurality of different operating configurations, each of the plurality of different operating configurations being configured to direct the flow of liquid solvent to a corresponding one of the plurality of sample cells during a corresponding time period of each supply cycle. It will be appreciated that the time taken to switch between the various operating configurations is itself very small and the switching time between the various supply cycles is also very short and therefore negligible. The term "corresponding time period" refers herein to the time period or duration associated with the corresponding sample cell to be directed to in the supply cycle. Herein, the term "operating configuration" refers to a configuration in which communication between different ports of the switching valve, e.g. a first port communicates with a fourth port in one operating configuration and a first port communicates with a sixth port in another operating configuration.

It will be appreciated that in some embodiments, only liquid solvent may flow through the switching valve 115, i.e., gas and liquid solvent may be mixed downstream of the switching valve 115. Thereby, it is possible to avoid the durability of the switching valve 115 from being affected by the flow of the gas-liquid mixture through the switching valve 115. In other embodiments, however, the gas and liquid solvent may be mixed upstream of the switch valve 115 such that the gas-liquid mixture flows into the sample cell via the switch valve 115.

In some embodiments, the switching valve 115 may include a first port in communication with the second supply line 112 (upstream thereof) or the solvent pump 113, and may also include a plurality of ports in fluid communication with a plurality of sample wells, respectively. The liquid solvent may flow from the first port into the switching valve 115 and then flow to the sample cell through one of the ports, so as to switch the flow path of the liquid solvent. In this case, the operation configuration may refer to a state in which the first port of the switching valve 115 is in fluid communication with one of the plurality of ports. The plurality of operating configurations may refer to a plurality of states in which the first port of the switching valve 115 is in fluid communication with the plurality of ports, respectively. Of course, the invention is not limited thereto, and other states of the switch valve 115 are also contemplated to constitute the above-described operational configuration. According to the present invention, the controller may be configured to place the first port in fluid communication with one of the plurality of ports during a corresponding time period of each supply cycle of the liquid solvent or mixture to the sample cell to direct the flow of the liquid solvent to a sample cell of the plurality of sample cells corresponding to the one port.

For example, during a first period of the supply cycle, the switch valve 115 may be in its first operational configuration to supply the liquid solvent (or a mixture thereof with a gas) to a first one 122a of the plurality of sample cells, during a second period of the supply cycle, immediately thereafter, the switch valve 115 may be in its second operational configuration to supply the liquid solvent (or a mixture thereof with a gas) to a second one 122b of the plurality of sample cells, such that the liquid solvent (or a mixture thereof with a gas) is similarly supplied to the third and fourth sample cells during a subsequent third and fourth period of the same supply cycle. That is, the switch valve 115 may be in the third and fourth operating configurations. If there are multiple supply cycles, after the last time period of the aforementioned one supply cycle supplies liquid solvent (or a mixture thereof with gas) to the last one of the multiple sample cells, the first time period of the next supply cycle is continued, returning to supplying liquid solvent (or a mixture thereof with gas) to the first sample cell 122 a. And so on until all of the given supply cycles or supply cycles are completed.

The use of the switching valve 115 to switch between the individual sample cells (e.g., 122a-122 d) may also result in a reduced number of parts as compared to providing one switching device or valve for each sample cell.

As described above, in order to supply a gas or a mixture of a liquid solvent and a gas to a sample cell in a predetermined order, the first supply module 110 of the present invention may include a switching device as a first supply control device to make and break a flow path therethrough. In the case where the extraction module comprises a plurality of sample cells (e.g., 122a-122 d), the first supply module 110 of the present invention has, on the one hand, a first supply line 111 comprising a plurality of branch lines and, on the other hand, a plurality of switching means in corresponding communication with the plurality of branch lines. Advantageously, each of the plurality of switching devices is in communication with a corresponding one of the plurality of branch lines (e.g., each switching device is disposed on one of the branch lines as shown in FIG. 1) such that the one of the branch lines is in selective fluid communication with a corresponding one of the plurality of sample wells.

Due to the arrangement of the switching means in one supply cycle, a guiding of the gas flow in the segment to a corresponding one of the plurality of sample cells can be achieved. In particular, in a first operating configuration of any one of the plurality of switching devices, one of the branch lines in corresponding communication with the any one of the plurality of switches is in fluid communication with a corresponding one of the plurality of sample cells, while in a second operating configuration of any one of the switching devices, the one of the branch lines is not in fluid communication with the corresponding one of the plurality of sample cells.

The controller according to the invention may be configured to, in each supply cycle of gas or mixture to the sample cells, place each of the plurality of switching devices sequentially in its first operating configuration while the remaining switching devices of the plurality of switching devices are in their second operating configuration, to supply gas (or gas in a gas-liquid mixture) sequentially (preferably in a predetermined order) to each of the plurality of sample cells.

In some embodiments, during a first period of the supply cycle, the second switching device 116b on the second branch line 111b in the first supply line 111 may allow fluid to flow therethrough to supply gas (or a mixture thereof with a liquid solvent) to the first sample cell 122a of the plurality of sample cells. During a second period immediately following the supply cycle, the third switching device 116c on the third branch line 111c in the first supply line 111 allows fluid to flow through it (at which point the first switching device prevents fluid from flowing through it) to supply gas (or a mixture thereof with liquid solvent) to the second sample cell 122b of the plurality of sample cells. The third and fourth sample cells 122c and 122d are similarly supplied with gas (or a mixture thereof with a liquid solvent) during the subsequent third and fourth periods of the same supply cycle. If there are multiple supply cycles, after the last time period of the aforementioned one supply cycle supplies gas (or a mixture thereof with liquid solvent) to the last one of the multiple sample cells, the first time period of the next supply cycle is continued, returning to supplying gas (or a mixture thereof with liquid solvent) to the first sample cell 122 a. And so on until all of the given supply cycles or supply cycles are completed.

Although the switching device can be configured as a valve, other known mechanical structures are possible that can be switched on and off. However, it is understood that the switching device is not limited to be implemented to perform the function of switching the flow path only, and may be, for example, an opening-adjustable device, which will not be described herein. It should be noted that the gas supply step according to the invention may also be performed without the aid of the switching means described above.

Furthermore, the present invention contemplates the use of the switching valve 115 in combination to achieve sequential purging of the sample cells (e.g., 122a-122 d). In this case, it is necessary to fluidly connect the first supply line 111 for supplying the gas with the switching valve 115 (the first branch line 111a of the first supply line 111 as shown in fig. 1 may be connected to the switching valve 115) so that the gas as the purge gas flows from the first supply line 111 to the sample cells via the switching valve 115, i.e., sequentially to the respective sample cells. At this time, the gas flow control device 114 may be in the aforementioned fully open mode, and the regulating device in its non-operating mode (opening maximized) to reduce the difference in flow resistance on each branch line, thereby facilitating nearly identical purging of the individual sample cells. Further, instead of using a plurality of switching devices (e.g., first to fourth switching devices) in communication with the first supply line 111, the present invention may also implement sequential air supply to the extraction module and/or the evaporation module by means of a combination of the first supply line 111 and the switching valve 115 to achieve desired cleaning, purging, air blowing, etc.

In correspondence with multiplex or multichannel extraction, multiplex evaporation can be performed on-line. In the case of multiple evaporation, when evaporation is performed by depressurization, for example, vacuum may be provided by an external vacuum pump, vacuum may be transferred into the evaporation vessel by using a vacuum manifold which may distribute the vacuum paths for the respective multiple channels, i.e. each vacuum tube path in the first to fourth vacuum lines is preferably provided with a vacuum valve 144 to control the evaporation process individually. These vacuum valves 144 are necessary for evaporating a fixed volume, whereas for general evaporation they may not be needed.

In the case of multiple evaporation, when evaporation is performed by heating, the heating of the evaporation vessel is heat conduction or microwave heating or other known forms of heating. The evaporation module comprises first heating means for evaporating the liquid solvent containing the analyte located therein by heating the evaporation vessel. In the case of multiple evaporation, the number of first heating means may be determined by the number of evaporation vessels. Furthermore, the first heating means may also be controlled individually by each evaporation vessel.

In the case of multiple vaporization, when vaporization is performed by blowing or bubbling, the blowing of the multiple vaporization containers may be a gas flow provided by means of an external gas source 152. The external gas may be distributed to the respective vaporization containers by a flow divider. As already mentioned above, the gas used for the blowing may be the same gas source 152 as the gas supplied to the sample cell, and a plurality of branch lines of the aforementioned first supply line 111 may also be utilized. Preferably, each branch gas path, whether or not in common with the supply of gas to the sample cell, is individually controllable by a valve that can switch the flow of gas.

In the following, exemplary steps of the method of the present invention are explained with reference to the four-way extraction embodiment shown in fig. 2. It should be noted that the illustrated process is merely exemplary, as the devices, parameters, and even some of the steps employed therein are exemplary or optional. For example, fig. 2 does not show the sub-step of supplying pre-filled (high pressure) gas before supplying (only) liquid solvent.

1) The device is initialized to bring the controller of the present invention and the various means into operation.

2) Samples (e.g., fixed or semi-solid samples) may be loaded into the four sample cells, respectively (see fig. 2). It will be appreciated that in other embodiments, the sample may be pre-integrated into the sample cell (e.g., 122a-122 d). Alternatively, at least a portion of the sample may also be reloaded into the sample cells after the extraction process has begun, in particular into some of the four sample cells.

3) The four sample cells (e.g., 122a-122 d) may be heated until a target temperature (e.g., a temperature value in the range of 40-200 degrees celsius) is reached (raised). For example, the sample cell may be loaded into an extraction heating device (e.g., an oven) by means of an automated pneumatic gantry. Alternatively, the sample cell may also already be located in the extraction heating device, for example the extraction heating device may be integrated into the extraction module. With the aid of the dotted area of fig. 2, the heating can continue throughout the sub-step process of supplying (only) liquid solvent. This is merely exemplary, however, and it is also possible, for example, to supply the gas-liquid mixture before the process or continuously after the process.

4) The regulating means (if any) is put in an operating mode and the gas flow control means 114 (if any) is put in a fully open mode to supply only (high pressure) gas (not shown in fig. 2) to the sample cell. Thus, the pressure in the sample cell can be rapidly increased to a preset pressure. The preset pressure may be between 100-500psi, such as 220psi. In the case of four sample cells, the gas is supplied to each sample cell in a predetermined order (e.g., to the first, second, third, and fourth sample cells) for about 15 seconds, i.e., one supply period lasts for about 60 seconds. It is possible that only one supply cycle of gas has been supplied up to the first preset pressure, so that no further subsequent supply of gas is necessary for the pre-filling, but this is merely exemplary.

5) After the interior of the cuvette has been raised to a first preset pressure, a liquid solvent is supplied to the cuvette, for example pumped by means of a solvent pump 113. In embodiments comprising four sample cells (e.g., 122a-122 d), each sample cell may be filled with liquid solvent once, i.e., a specified volume of liquid solvent is continuously filled at a maximum pump speed, but alternatively liquid solvent may be supplied to each of the plurality of sample cells in multiple supply cycles, with the latter being preferred. In the embodiment of fig. 2, the liquid solvent is supplied to each of the four sample cells in a predetermined order (e.g., to the first, second, third, and fourth sample cells) for about 15 seconds, i.e., one supply period lasts about 60 seconds. At this time, the flow rate of the liquid solvent is large, preferably up to 40 ml/min, so that the sample cell is rapidly filled with enough solvent to avoid dry burning of the sample. Although fig. 2 shows four supply cycles, other numbers of supply cycles are also contemplated such that each sample cell is supplied with a first preset amount of liquid solvent.

6) The sample cell may then be supplied with a mixture of liquid solvent and gas. The gas and liquid solvents are mixed well before entering the sample cell. The gas flow control device 114 may be in a gas flow control mode so as to supply a preset flow of gas (in the form of a mixture with a liquid solvent) to the sample cell (e.g., the preset flow of gas may be supplied to the mixing device 117 of the first supply module 110). In one example, the gas flow rate may be 0-200 ml/min and the liquid solvent flow rate may be 0.5-80 ml/min. In the embodiment of fig. 2, the gas-liquid mixture is supplied to each of the four sample cells in a predetermined order (e.g., to the first, second, third, and fourth sample cells) for about 15 seconds, i.e., one supply period lasts for about 60 seconds. At this time, the flow rate of the liquid solvent is small compared with the previous step, for example, 0.5 to 40 ml/min, to promote the diffusion of the gas-liquid mixture in the sample cell. Although fig. 2 shows four supply cycles, other numbers of supply cycles (e.g., up to 100) are also contemplated until a preset amount or time of gas-liquid mixture has been supplied.

7) After the liquid solvent containing the analyte flows from the sample cell (e.g., via the conditioning device) into a subsequent device, such as an evaporation vessel, evaporation of the liquid solvent within the evaporation vessel may begin (not shown in fig. 2).

8) The sample cell (e.g., high pressure nitrogen) may be purged with a purge gas after a predetermined amount of liquid solvent is collected in the vaporization vessel (e.g., 141a-141 d) or after a predetermined vaporization time has elapsed (but other predetermined conditions may be met) (see right-most side of fig. 2). At this time, the regulator is in its non-operating state (opening degree is maximum), and the vacuum valve 144 of the evaporation module is closed. Thereby, residual analytes residing in the sample cell can be collected into the evaporation vessel. In the embodiment of fig. 2, it can be seen that the four sample cells are purged simultaneously, rather than sequentially.

9) After the purge is complete, the regulating device may be placed back in the operational mode and evaporation of the liquid solvent within the evaporation vessel (e.g., 141a-141 d) may continue. In an embodiment that evaporates a fixed volume, the level sensing module continues to record the level of liquid solvent in the evaporation vessel (e.g., evaporation vial).

In fig. 2, each dark grid represents an operation performed on a respective sample cell or channel, while the light grid represents no operation performed on a respective sample cell or channel (e.g., in a static extraction state). It is noted that the time for supplying fluid (gas, liquid solvent or gas-liquid mixture) to each sample cell in one supply cycle is about the same (i.e., about 15 seconds) in fig. 2, but it is also contemplated in other embodiments that the duration of one supply cycle is different in each supply sub-step (e.g., 60 seconds when pre-filled with gas, 100 seconds when liquid solvent is supplied, etc.). But preferably the time to supply to each sample cell is the same or the supply amounts are equal in one supply cycle. More preferably, the time of supply to each cell is short, for example within 30 seconds (e.g. 10-20 seconds), to ensure consistent extraction conditions from cell to cell, without the conditions changing within the cells that are not supplied due to the long time. In addition, the above-described method and apparatus of the present invention may be extended from four channels to six or eight channels, or reduced to two channels. Furthermore, other numbers of channels, such as an odd number of channels, are also contemplated.

In a preferred embodiment, for a multi-channel sample cell, an extraction heating device, such as a furnace, may be first brought into heating (e.g., to a target temperature) and then the individual sample cells are loaded into the extraction heating device in sequence at intervals (e.g., 15-20 seconds apart) such that the points in time at which gas and liquid solvents are supplied to each sample cell are in close proximity on the temperature rise curve for the samples in that sample cell, thereby achieving more consistent extraction conditions.

With the method and apparatus of the present invention, it is also possible to increase the throughput (at least 2.5 times) while ensuring recovery, for example, see the following comparative table.

Table 1: comparison of the treatment flux of the present invention with the prior art

Furthermore, in experiments, for example, comparing the recovery of fat content of infant milk powder samples, by means of the method and apparatus of the present invention (mainly by pre-filling with gas, then impregnating with liquid solvent and finally solvent extraction with gas assist), the extraction recovery can be increased from 55-70% to more than 90% compared to the prior art, where other conditions (such as solvent type, solvent amount, temperature, pressure, extraction time, etc.) remain the same.

In addition, in another embodiment of four-channel extraction, the sample is acetone/dichloromethane (50%/50%), the extraction heating temperature is 100 degrees celsius, the total extraction time is 20 minutes, the cell volume is 100 milliliters, the purge time is 180 seconds, and the flow rate of the liquid solvent when the gas-liquid mixture is supplied is 0.75 milliliters/minute. Under such conditions, the use of liquid solvents can be reduced by more than 50% compared to the prior art with satisfactory recovery rates obtained by the method and system of the present invention.

In the following, the system and its equipment in some examples, in particular its supply flow path, are described in detail with the aid of fig. 1.

The gas, particularly an inert gas such as high pressure nitrogen, may be split into two gas paths after exiting from gas source 152. The first path is for a first supply line 111 of the first supply module 110, while the second path may be for other supply modules not described in detail herein (not specifically illustrated herein). The first gas flow passes to the gas flow control device 114 via an optional filter 153. After flowing through the gas flow control device 114, the first supply line 111 can be divided into five branch lines 111a-111e by means of a first manifold, wherein a switching device 116a-116e, for example a valve, can be provided on each branch line.

The liquid solvent may come from a number of different solvent containers, and the liquid solvent in these containers may be mixed (e.g., with the aid of a mixing valve) before flowing into the second supply line 112 of the first supply module 110. The solvent pump 113 pumps the liquid solvent (whether mixed or not) to the switching valve 115. As can be seen from fig. 1, the gas flowing through the first switching device 116a provided on the first branch pipe (also referred to as a main gas path) 111a may be mixed with the liquid solvent that does not flow through the switching valve 115, but may also flow through the switching valve 115 directly without mixing. The gas flowing through the second to fifth switching devices 116b to 116e provided on the second to fifth branch lines 111b to 111e may be mixed with the liquid solvent flowing through the switching valve 115 inside the mixing device 117.

More specifically, when only gas is supplied to the sample cell, a first branch line (main gas line) 111a in the first supply line 111 may be preferably employed. From the first branch line 111a, the gas may flow to the switching valve 115, and by means of the switching valve 115, it is subdivided into four sub-gas paths, which may be simultaneously or sequentially supplied to the first to fourth sample cells 122a to 122d, to rapidly raise the pressure in the sample cells. It will be appreciated that when supplying only gas to the sample cell and/or evaporation vessel, instead of the main gas path, four branch lines 111b-111e may be used so that the gas does not pass through the switch valve 115 and is split into four gas paths before the mixing device 117.

When only the liquid solvent is supplied to the sample cell, the liquid solvent may be pumped to the switching valve 115 by means of the solvent pump 113, and may be divided into four sub-liquid paths by means of the switching valve 115, and thus may be simultaneously or sequentially supplied to the first to fourth sample cells to rapidly infiltrate or wet the sample in the sample cell, avoiding the sample from being dry-burned in the sample cell.

When a mixture of liquid solvent and gas is supplied to the sample cell, on the one hand, the liquid solvent can be pumped by means of the solvent pump 113 to the switching valve 115, by means of which switching valve 115 it is divided into four sub-liquid paths via which the liquid solvent flows into the mixing device 117. On the other hand, the gas also flows into the mixing device 117 via the second to fifth branch lines 111b to 111e to be mixed with the liquid solvent therein. The mixed gas-liquid mixture flows from the mixing device 117 to the first to fourth sample cells via the first to fourth mixing supply lines, thereby dissolving analytes in the samples therein. In other words, the mixture may be supplied to the first to fourth sample cells 122a to 122d simultaneously or sequentially. It will be appreciated that the supply lines may be referred to as part of the first supply line 111 when only gas is supplied and the supply lines 112a-112d may be referred to as part of the second supply line 112 when only liquid solvent is supplied.

The liquid solvent containing the analyte may enter the first through fourth evaporation vessels 141a-141d from the first through fourth sample tanks 122a-122d, respectively, via the respective adjustment devices 130a-130d, and begin to evaporate when evaporation is required to obtain the desired concentrate.

As can be seen in FIG. 1, the first through fourth vacuum lines 142a-142d are in fluid communication with the first through fourth vaporization containers 141a-141d to rapidly decompress and vaporize the interiors of the first through fourth vaporization containers 141a-141 d. Here, the first to fourth evaporation containers 141a to 141d include an evaporation flask located above and an evaporation vial (also referred to as a sample vial) located below, respectively. Advantageously, a plurality of evaporation vessels may be arranged on the automatic rotation device to facilitate subsequent replacement or monitoring.

In addition, the first to fourth evaporation containers (or a part thereof) may be supplied with gas by means of the first supply module 110 (via the sample cell) to perform the aeration or the blowing. In addition, a purge gas may also be provided to the first through fourth sample cells 122a-122d by means of the first supply module 110 to further collect the residual analytes remaining in the first through fourth sample cells 122a-122d into the first through fourth evaporation vessels 141a-141 d.

While various embodiments of the invention are described in the figures with reference to examples of sample preparation systems comprising gas-assisted solvent extraction techniques and methods of collecting analytes from samples by means of the sample preparation systems, it should be understood that embodiments within the scope of the invention may be applied to systems, devices and methods having similar structures and/or functions.

The foregoing description has provided numerous features and advantages including various alternative embodiments, as well as details of the structure and function of the devices and methods. The intent herein is exemplary and not exhaustive or limiting.

It will be apparent to those skilled in the art that various modifications can be made in the full scope indicated by the broad general meaning of the terms expressed in the appended claims, especially in matters of structure, material, elements, components, shapes, sizes and arrangements of parts, including combinations of parts within the principles described herein. To the extent that such modifications do not depart from the spirit and scope of the appended claims, they are intended to be included therein.

Claims

1. A method of extracting an analyte from a sample by a sample preparation system comprising an extraction module comprising a sample cell for holding a sample containing the analyte, the method comprising the sequential steps of:

a) Supplying gas to the sample cell with the sample placed therein to raise the interior of the sample cell to a first preset pressure;

b) Supplying a liquid solvent capable of dissolving an analyte in the sample to the sample cell to a first preset amount;

c) Supplying a mixture of the gas and the liquid solvent to the sample cell;

wherein heating of the sample cell is started before step b.

2. The method of claim 1, wherein the extraction module comprises a plurality of sample cells, wherein step a comprises supplying gas to each of the plurality of sample cells to raise the interior of each sample cell to the first preset pressure.

3. The method of claim 1, wherein the extraction module comprises a plurality of sample cells, wherein step b comprises the sub-steps of:

b1 Supplying the liquid solvent to each of the plurality of sample cells in a predetermined order;

b2 Step b 1) is repeatedly performed so that the liquid solvent supplied to each sample cell reaches the first preset amount.

4. The method of claim 1, wherein the extraction module comprises a plurality of sample cells, wherein step c comprises the sub-steps of:

c1 Supplying the mixture to each of the plurality of sample cells in equal amounts in a predetermined order;

c2 Step c 1) is repeatedly executed until a preset stop condition is reached.

5. The method of claim 4, wherein the preset stop condition is a first preset time or a second preset amount of the mixture.

6. The method of claim 1, wherein heating of the sample cell is initiated prior to step a.

7. The method of claim 1, wherein the flow rate of the liquid solvent into the sample cell in step b is greater than the flow rate of the liquid solvent in the mixture into the sample cell in step c.

8. The method according to claim 1, wherein in step c, the mixing ratio of the gas and the liquid solvent is 1% to 20%.

9. The method of claim 1, wherein the first predetermined amount in step b is greater than 20% of the volume of the sample cell or the first predetermined amount is an amount that causes greater than 70% of the sample in the sample cell to be infiltrated by the liquid solvent.

10. The method of claim 1, wherein the first predetermined pressure is 200-500psi.

11. The method according to claim 1, wherein in step c a predetermined flow rate of gas is mixed with the liquid solvent to supply the mixed mixture to the sample cell.

12. A sample preparation system for extracting an analyte from a sample, comprising:

an extraction module, the extraction module comprising:

a sample cell for holding a sample containing an analyte; and

extraction heating means for heating the sample cell;

a first supply module capable of supplying a gas and a liquid solvent capable of dissolving an analyte in the sample to the sample cell, wherein the first supply module comprises:

a first supply line for supplying a gas;

a second supply line for supplying a liquid solvent;

a first supply control device in fluid communication with the first supply line and having a first operating configuration that allows the first supply line to supply gas to the sample cell and a second operating configuration that prevents the first supply line from supplying gas to the sample cell;

a second supply control device in fluid communication with the second supply line and having a first operating configuration that allows the second supply line to supply liquid solvent to the sample cell and a second operating configuration that prevents the second supply line from supplying liquid solvent to the sample cell;

A controller configured to:

placing the first supply control device in its first operating configuration such that gas flows into the sample cell and placing the second supply control device in its second operating configuration;

placing the first supply control device in its second operating configuration and placing the second supply control device in its first operating configuration after the interior of the sample cell has been raised to a first preset pressure, wherein the extraction heating device is controlled to heat the sample cell before the first supply control device and the second supply control device change their operating configurations; and

after the first supply module supplies the liquid solvent to the sample cell for a first preset amount, the first supply control device is placed in its first operational configuration to supply the mixture of gas and liquid solvent to the sample cell.

13. The sample preparation system of claim 12, wherein the second supply control device is configured as a solvent pump for pumping the liquid solvent, the solvent pump pumping the liquid solvent to the sample cell in the first operational configuration of the solvent pump, and the solvent pump not pumping the liquid solvent to the sample cell in the second operational configuration of the solvent pump.

14. The sample preparation system of claim 12, wherein the extraction module comprises a plurality of sample cells, the first supply module comprises a switching valve comprising a first port for inflow of the liquid solvent and a plurality of ports respectively in corresponding communication with the plurality of sample cells, the controller configured to place the first port in fluid communication with one of the plurality of ports to direct the flow of the liquid solvent to a sample cell of the plurality of sample cells corresponding to the one port during a corresponding time period of each supply cycle of the liquid solvent or the mixture to the sample cell.

15. The sample preparation system of claim 14, wherein the first supply line comprises a plurality of branch lines respectively corresponding to the plurality of sample cells, the first supply control device comprises a plurality of switch devices respectively corresponding to the plurality of branch lines, wherein in the first operational configuration of any one of the plurality of switch devices, one branch line corresponding to the any one switch is in fluid communication with a corresponding one of the plurality of sample cells, and in the second operational configuration of any one switch device, the one branch line is not in fluid communication with the corresponding one of the plurality of sample cells.

16. The sample preparation system of claim 15, wherein the controller is configured to sequentially place each of the plurality of switching devices in its first operational configuration while the remaining switching devices of the plurality of switching devices are in their second operational configuration to sequentially supply the gas to each of the plurality of sample cells during each supply cycle of the gas or the mixture to the sample cells.

17. The sample preparation system of claim 12, wherein the first supply module further comprises a gas source and/or a solvent source.

18. The sample preparation system of claim 15, wherein the first supply module further comprises a mixing device within which the liquid solvent and the gas are mixed such that the first supply module can supply the mixture to the sample cell.

19. The sample preparation system of claim 18, wherein in the first supply module, the mixing device is disposed closer to the sample cell than the switching valve and the switching device.

20. The sample preparation system of claim 12, wherein the first supply module further comprises a solvent pump for pumping the liquid solvent, the solvent pump being configured to pump at a greater flow rate when the first supply module supplies only the liquid solvent to the sample cell than when the mixture is supplied to the sample cell.