Flow limiting pneumatic modulator for multi-dimensional gas chromatography system

Abstract

A flow limiting pneumatic modulator (FRPM) assembly for a multi-dimensional gas chromatography system includes a first y-shaped fluid connector, the first y-shaped fluid connector has a first inlet to receive flow from the first chromatography column, a first passage having a flow blocker member and a first outlet, and a second passage having a second outlet in fluid communication with a downstream bypass line. The FRPM assembly also has a second y-shaped fluid connector having a second inlet in fluid communication with the first outlet, a third inlet in fluid communication with an auxiliary flow, and a third channel having a third outlet in fluid communication with a second chromatographic column. The FRPM assembly also has at least one flow control valve that can operate as an injector and modulator of the second chromatography column. Methods of chromatographic analysis of a fluid sample comprising one or more target analytes in a multi-dimensional chromatography system are also provided.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This PCT international application claims the benefit of U.S. Provisional Application No. 63 / 354,520, filed on June 22, 2022. The entire disclosure of the above application is incorporated herein by reference.

[0003] Government support

[0004] This invention was made with government support under OH011082 from the Centers for Disease Control and Prevention, TR003812 from the National Institutes of Health, and FA8650-19-C-9101 from the Office of the Director of National Intelligence - Intelligence Advanced Research Projects Agency. The government has certain rights in this invention. Technical Field

[0005] The present disclosure relates to a limiting flow pneumatic modulator for a multidimensional gas chromatography system and a method for performing multidimensional chromatography analysis using the limiting flow pneumatic modulator. Background Art

[0006] This section provides background information related to the present disclosure which is not necessarily prior art.

[0007] Compared to conventional gas chromatography, micro-gas chromatography (μGC) is performed on a miniaturized scale. μGC is a powerful portable vapor analysis method used in applications such as environmental protection and monitoring, workplace hazard analysis, and biomedicine. To date, almost all μGC devices are one-dimensional (1D) GCs with relatively short (<10m) columns, which limits the separation performance of complex mixtures for many field applications (e.g., petroleum, food, metabolomics, or forensics), which may require the separation of hundreds of different compounds. Therefore, there is a need to add a second column to two-dimensional (2D) GC (e.g., heart-cutting or comprehensive 2D GC) to further enhance the separation capability and expand the range of compounds that can be analyzed by a single portable μGC device.

[0008] A multidimensional gas chromatography system includes at least two different chromatographic columns connected in series. A special type of μGC is a comprehensive two-dimensional (2-D) gas chromatography ("GC×GC"), which is very suitable for analyzing and separating complex mixtures of volatile and / or semi-volatile compounds. Typically, a comprehensive 2-D GC utilizes two columns of different selectivity connected in series by an injector device. Typically, in GC×GC separation, a sample is introduced into a first chromatographic column via injection. The target analyte substance elutes from the first column and can be captured or periodically sampled by a downstream injector device. In a 2-D GC device, the injector disposed between the first dimension column and the second dimension column is an important component. The injector cuts a portion of the eluent from the first dimension GC column and injects the eluent into the second dimension column for further analysis. When the injector periodically performs the above operation, it is also called a "modulator", which is commonly used in comprehensive 2-D GC.

[0009] The injector or modulator device is placed on the first column ( 1 D) and the second column ( 2 D), for continuously capturing and concentrating components eluted from the first column and re-injecting these components into the second column (as a continuous injector for the second column). Thus, after collecting the eluted material from the first column, a typical modulator periodically injects the collected contents into the second column at predetermined regular intervals (e.g., typically at intervals ranging from 2 seconds to 5 seconds). Such injected fragments can be separated in the second column and eluted into a downstream detector, where they can be identified and / or measured.

[0010] In general, there are two types of modulators: (1) thermal modulators and (2) pneumatic modulators. Thermal modulators rely on a trap to first cut and capture a portion (e.g., 2 seconds) of the eluate from the first dimension column, and then inject the captured analyte into the second dimension column in the form of a spike by rapidly raising the temperature. In addition, in order to capture subsequent eluate from the first dimension column, the thermal modulator needs to be cooled immediately. The main disadvantages of thermal modulators are the need for (1) high power to achieve rapid temperature ramping and (2) a rapid cooling mechanism (usually based on the thermoelectric cooling effect or the use of liquid nitrogen or CO 2 ), which makes the modulator bulky and difficult to operate. These increase the modulator's footprint and are therefore not suitable for μGC development. In addition, the injection peak width is limited due to the thermal mass. Although a microfabricated thermal modulator using thermoelectric cooling has been recently demonstrated, it is still power-hungry, difficult to manufacture and maintain, and cannot capture light compounds.

[0011] In contrast, pneumatic modulators rely on an auxiliary flow to control the injection of the eluate from the first dimension column into the second dimension column. Pneumatic modulators use external valves and auxiliary flows to inject a portion of the eluate from the first dimension column into the second dimension column without the need for rapid heating or cooling. The advantages of pneumatic modulators include (1) no need for rapid heating and cooling, and (2) sharper injection peaks (e.g., the peak width is limited by the valve that controls the switching of the auxiliary flow). Several types of conventional pneumatic modulators are commonly used. The first is a stopped flow modulator, in which a flow is stopped when the second dimension ( 2 D) column separation, the first dimension ( 1 D) Flow within the column is temporarily stopped. Although stopped-flow modulators (essentially T-junctions) can be microfabricated, the use of stopped-flow mode significantly increases the first dimension ( 1 D) column separation time and cause additional peak broadening. Pneumatic flow switch modulators such as the Deans switch are also widely used and have been microfabricated for comprehensive 2DGC. Although Capillary Flow Technology allows continuous first dimension ( 1 D) Column separation with the second dimension ( 2 D) column separation, but requires careful adjustment of the first dimension ( 1 D) Column and second dimension ( 2 D) flow rate in the column to avoid the first dimension ( 1 D) reflux in the column. Additionally, due to the first dimension ( 1 D) Column eluate is transferred to the second dimension ( 2 D) Auxiliary flow required for the column, the second dimension ( 2 D) The analyte concentration in the column is diluted. The differential flow modulator uses a 4-port valve or a 6-port valve so that the first dimension ( 1 D) Column flow and second dimension ( 2 D) Column flows are independent and thus allow for concomitant first dimension ( 1 D) Column and second dimension ( 2 D) column separation, while allowing high second dimension ( 2 D) Column and first dimension ( 1 D) Column flow rate ratio for rapid second dimension ( 2 D) Column injection and improved second dimension ( 2 D) Column separation. However, 4-port valves and 6-port valves are very large and heavy, and they are not suitable for μGC. Therefore, it is desirable to develop a pneumatic modulator for a multidimensional gas chromatography system that is relatively lightweight and compact while providing excellent performance. Summary of the invention

[0012] This section provides a general summary of the disclosure, and is not a comprehensive disclosure of its full scope or all of its features.

[0013] In certain aspects, the present disclosure relates to a flow-restricted pneumatic modulator (FRPM) component for a multidimensional gas chromatography system. The FRPM component may include a first y-shaped fluid connector. The first y-shaped fluid connector has a first inlet, a first channel with a first outlet, and a second channel with a second outlet. The first inlet is configured to receive a flow from a first chromatographic column. The first outlet is configured to be in fluid communication with a second chromatographic column. The second outlet is configured to be in fluid communication with a bypass line downstream. The FRPM component also includes a first flow blocker component, the first flow blocker component being arranged in the first channel, the first channel having a first flow resistance to the flow. The second channel has a second flow resistance, the second flow resistance being less than the first flow resistance. The FRPM component also has at least one flow control valve, the at least one flow control valve being in fluid communication with the second outlet of the first y-shaped fluid connector. The FRPM component also includes a second y-shaped fluid connector, the second y-shaped fluid connector having a second inlet and a third inlet, the second inlet and the third inlet being connected to a third channel having a third outlet. The second inlet is in fluid communication with the first outlet of the first y-shaped fluid connector and is configured to receive flow from the first chromatographic column. The third inlet is configured to be in fluid communication with an auxiliary flow conduit upstream of the restricted flow pneumatic modulator assembly, and the third outlet is configured to be in fluid communication with the second chromatographic column. The restricted flow pneumatic modulator assembly is configured to operate as an injector and modulator for the second chromatographic column.

[0014] In one aspect, the second channel comprises a second flow resistor component, the second flow resistor component exhibiting the second flow resistance.

[0015] In one aspect, the FRPM component is formed on a substrate.

[0016] In one aspect, the at least one flow control valve is a first flow control valve and the flow limiting pneumatic modulator assembly further comprises a second flow control valve located upstream of and in fluid communication with the third inlet of the second y-shaped fluid connector.

[0017] In another aspect, the first flow control valve and the second flow control valve are each two-port valves each having an open position and a closed position.

[0018] In another aspect, in the first operating mode of the FRPM assembly, the first flow control valve and the second flow control valve are closed to direct the flow through the first channel, the first flow blocker component, the first outlet to the third channel and the third outlet, and are configured to direct the flow to the second chromatographic column. In the second operating mode of the FRPM assembly, the first flow control valve and the second flow control valve are open to direct the flow through the second channel and the second outlet, and are configured to direct the flow to the bypass line. The auxiliary fluid from the auxiliary flow conduit flows through the first flow blocker component and minimizes or prevents the fluid from flowing through the first channel and the first outlet toward the second chromatographic column, and the first flow blocker component minimizes any interference caused by the flow of the auxiliary fluid in the flow in the first chromatographic column.

[0019] In one aspect, the at least one flow control valve comprises a three-way valve.

[0020] In certain aspects, the present disclosure also relates to a multidimensional gas chromatography device. The multidimensional gas chromatography device includes a first chromatographic column, which receives a fluid sample, and the fluid sample includes one or more target analytes. The multidimensional gas chromatography device also includes a flow limiting pneumatic modulator (FRPM) component, which is arranged downstream of the first chromatographic column and is in fluid communication with the first chromatographic column, wherein the FRPM component receives a flow from the first chromatographic column. The FRPM component includes: a first y-shaped fluid connector, the first y-shaped fluid connector having a first inlet, a first channel having a first outlet, and a second channel having a second outlet; a first flow blocker component, the first flow blocker component is arranged in the first channel, the first channel has a first flow resistance to the flow, wherein the second channel has a second flow resistance to the flow, and the second flow resistance is less than the first flow resistance; and a second y-shaped fluid connector. The second y-shaped fluid connector has a second inlet, a third inlet, and a third channel having a third outlet. The second inlet is in fluid communication with the first outlet of the first y-shaped connector and receives the flow from the first chromatographic column. The FRPM component also includes at least one flow control valve. The multidimensional gas chromatography device also includes an auxiliary fluid pipeline, which is arranged upstream of the FRPM component. The third inlet of the second y-shaped fluid connector is in fluid communication with the auxiliary fluid pipeline. The multidimensional gas chromatography device also includes a second chromatographic column, which is arranged downstream of the FRPM component and is in fluid communication with the third outlet of the second y-shaped fluid connector. The FRPM component is configured to operate as an injector and modulator for the second chromatographic column. A bypass line is arranged downstream of the FRPM component and is in fluid communication with the second outlet of the first y-shaped fluid connector. At least one flow control valve controls the flow of the flow to the bypass line. The multidimensional gas chromatography device also includes at least one detector, which is used to detect the presence of one or more target analytes eluted from the flow after the flow passes through the second chromatographic column.

[0021] In one aspect, the at least one flow control valve is a second flow control valve, the second flow control valve is in fluid communication with the second outlet of the first y-shaped fluid connector. The multidimensional gas chromatography apparatus also includes a first flow control valve, the first flow control valve is disposed upstream of the FRPM assembly, the first flow control valve is in fluid communication with the third outlet of the second y-shaped fluid connector.

[0022] In yet another aspect, the first flow control valve and the second flow control valve are each two-port valves each having an open position and a closed position.

[0023] In another aspect, in the first operating mode of the FRPM assembly, the first flow control valve and the second flow control valve are closed to direct the flow through the first channel, the first flow blocker component, the first outlet, the second inlet, and through the third channel to the third outlet to direct the flow to the second chromatographic column. In the second operating mode of the FRPM assembly, the first flow control valve and the second flow control valve are open to direct the flow through the second channel and the second outlet, and are configured to direct the flow to the bypass line, and the first flow blocker component minimizes or prevents fluid from flowing through the first channel and the first outlet toward the second chromatographic column.

[0024] In one aspect, the at least one flow control valve comprises a three-way valve.

[0025] In one aspect, the FRPM assembly further comprises a second flow blocker component disposed in the second channel of the first y-shaped fluid connector, the second flow blocker component having a second flow resistance that is less than the first flow resistance.

[0026] In one aspect, the FRPM component is formed in the substrate.

[0027] In another aspect, the substrate further includes: (i) a first chromatographic column located upstream of the FRPM component; (ii) a second chromatographic column located downstream of the FRPM component; or (iii) a first chromatographic column located upstream of the FRPM component and a second chromatographic column located downstream of the FRPM component.

[0028] In one aspect, the at least one detector comprises a photoionization detector (PID).

[0029] In one aspect, the multi-dimensional gas chromatography apparatus further comprises a second detector disposed downstream of the first chromatography column and upstream of the first inlet of the FRPM assembly.

[0030] In one aspect, the first chromatography column is a first micro gas chromatography column and the second chromatography column is a second micro gas chromatography column, wherein the multidimensional gas chromatography apparatus is portable.

[0031] In certain aspects, the present disclosure also relates to a method for chromatographic analysis of a fluid sample including one or more target analytes in a multidimensional chromatography system. The method includes: separating the one or more target analytes in the fluid sample in the first chromatographic column; and directing the flow leaving the first chromatographic column toward a flow-restricting pneumatic modulator (FRPM) assembly, which operates as an injector and modulator for a downstream second chromatographic column. The FRPM assembly includes a first y-shaped fluid connector, the first y-shaped fluid connector having a first inlet, a first channel having a first outlet, and a second channel having a second outlet. The first y-shaped fluid connector also has a first flow blocker component, the first flow blocker component is disposed in the first channel, and the first channel has a first flow resistance to the flow. The second channel has a second flow resistance to the flow, and the second flow resistance is less than the first flow resistance. The FRPM assembly also includes a second y-shaped fluid connector, the second y-shaped fluid connector having a second inlet, a third inlet, and a third channel having a third outlet. The second inlet is in fluid communication with the first outlet of the first y-shaped connector and receives the flow from the first chromatographic column. The FRPM component also includes at least one flow control valve. The method also includes operating the FRPM component for a first duration in a first operating mode, in which the at least one flow control valve is closed to selectively direct the flow through the first channel, through the first flow blocker component, through the first outlet to the second inlet, through the third channel and the third outlet to the second chromatographic column. The method also includes operating the FRPM component for a second duration in a second operating mode, in which the at least one flow control valve is open to direct the flow through the second channel and the second outlet and to a downstream bypass line.

[0032] In one aspect, the at least one flow control valve comprises: a first flow control valve, the first flow control valve being in fluid communication with the second outlet of the first y-shaped fluid connector upstream of the bypass line; and a second flow control valve, the second flow control valve being in fluid communication with the third inlet of the second y-shaped fluid connector. The first flow control valve and the second flow control valve are two-port valves each having an open position and a closed position.

[0033] In one aspect, the first duration is less than or equal to about 0.2 seconds.

[0034] In one aspect, in the first operating mode, the second chromatography column has a peak injection width of less than or equal to about 25 milliseconds.

[0035] In one aspect, the first flow rate of the stream in the first operating mode is less than or equal to about 0.5 milliliters per minute (mL / min), and the flow rate of the stream in the second operating mode is greater than or equal to about 1 mL / min.

[0036] In one aspect, the multidimensional chromatography system also includes an auxiliary fluid conduit, which is located upstream of the FRPM assembly. The at least one flow control valve includes a first flow control valve and a second flow control valve, and the second flow control valve is configured to receive an auxiliary fluid of the auxiliary fluid conduit upstream of the third inlet of the second y-shaped fluid connector. The auxiliary fluid conduit is in fluid communication with the second chromatographic column so that in the second operating mode, the auxiliary fluid flows through the first flow blocker component, and minimizes or prevents fluid from flowing toward the second chromatographic column through the first channel and the first outlet, and the first flow blocker component minimizes any interference caused by the auxiliary fluid flow in the flow in the first chromatographic column.

[0037] In one aspect, the flow entering the second chromatographic column during the first operating mode has a first flow rate, and the auxiliary fluid entering the second chromatographic column during the second operating mode has a second flow rate. The ratio of the second flow rate to the first flow rate is greater than or equal to about 10:1.

[0038] In one aspect, the method further comprises repeatedly operating the FRPM component in the first operating mode for the first duration and operating the FRPM component in the second operating mode for the second duration.

[0039] In one aspect, the FRPM component has a duty cycle of greater than or equal to about 1% to less than or equal to about 50%.

[0040] In one aspect, the method further comprises detecting one or more target analytes in the auxiliary flow exiting the second chromatography column.

[0041] In one aspect, the method further comprises detecting one or more target analytes in the flow exiting the first chromatography column.

[0042] Further areas of applicability will become apparent from the description provided herein.The description and specific examples in this summary are intended for purposes of illustration only and are not intended to limit the scope of the present disclosure. BRIEF DESCRIPTION OF THE DRAWINGS

[0043] The drawings described herein are for illustrative purposes only of selected embodiments and not all possible implementations, and are not intended to limit the scope of the present disclosure.

[0044] Figure 1An example of a multidimensional gas chromatography system having a flow restricting pneumatic modulator (FRPM) assembly prepared according to certain aspects of the present disclosure is shown, where the FRPM assembly can function as both an injector and a modulator.

[0045] Figure 2 A specific example of a multidimensional gas chromatography system having a FRPM component prepared according to certain aspects of the present disclosure is shown.

[0046] FIG. 3A to FIG. 3D Shows the use of Figure 2 Chromatograms obtained with the settings and multidimensional gas chromatography system parameters given in . The two traces in each subfigure, black (detector 1) and red (detector 2), represent the data acquired by detector 1 and detector 2, respectively. The modulation time was 2 s and the loading or cutting time was varied from 0.1 s to 0.4 s.

[0047] FIG. 4A to FIG. 4D A flow-restricted pneumatic modulator (FRPM) prepared according to certain aspects of the present disclosure for use in comprehensive 2D μGC operations is shown. Figure 4A Shows the case where both valves are closed 1 D to 2 D loading configuration (typical flow rate: approximately 1 mL / min). The blue arrows depict 1 D. Flow direction. Figure 4B Shows the high 2 D flow (typical flow rate: about 10 mL / min) with both valves open 2 D separation, achieving rapid 2 D injection and fast 2 D separation. Green arrows depict the auxiliary flow direction. Figure 4C A schematic diagram and description of the microfabricated FRPM is shown. The flow blocker is a narrow channel with a cross section of 40 μm x 170 μm (width x depth) and a length of 2 mm. All other channels have a cross section of 250 μm x 250 μm (width x depth). Figure 4D A FRPM module with a FRPM and two 2-port valves is shown. Ports 1 to 4 are labeled in both the schematic and the description.

[0048] FIG. 5A to FIG. 5D . Figure 5A Schematic diagram of a setup for characterizing a FRPM module prepared according to certain aspects of the present disclosure. The sample mixture was injected into a 10 m OV-1 coated microcolumn (μcolumn) having a cross section of 200 μm×250 μm (width×depth). A micro-photon ionization detector ( 1 DμPID) is connected to 1 Dμ column and monitor 1D eluate. 2 The DμPID was connected to the outlet of the FRPM module via a 20 cm guard column (inner diameter: 250 μm) and monitored 2 D eluate. Figure 1 Ports 1 to 4 are labeled on the FRPM module. Unmodulated operation at Fig.13A Shown in. Figure 5B Shows C 6 , C 7 , C 8 , benzene and toluene 1 D Chromatogram and 2 D Chromatogram. The time markers (shown as blue square waves) record the closed state (=0) and open state (=1) of the FRPM module valve, corresponding to 2 D load (=0) and 2 D separation (=1). Figure 5C It is C 7 exist 1 D and 2 Enlarged view in D. Figure 5D It is C 7 exist 2 Enlarged view in D. Experimental conditions: loading time = 0.25 s; modulation time = 2 s; 1 D Flow rate = 1.2 mL / min (measured at port 3 with both valves closed). 1 The flow rates measured at the outlet of D (before FRPM) are almost the same, indicating that the flow barrier has an 1 The effect of D flow can be neglected. 2 D Flow rate = 20 mL / min (measured at port 3 with both valves open). Fig. 13B Provided 1 Dμ column temperature ramp curve. FRPM is maintained at an isothermal ambient temperature (about 20°C). Helium is used as 1 D Both carrier gas and auxiliary flow.

[0049] FIG. 6A to FIG. 6D Shown by 2 DμPID detected C 6 , C 7 and C 8 of 2 D peak width (full width at half maximum) and 2 D / 1 D Flow rate ratio ( Fig. 6A ) and loading time ( Figure 6C ) relationship. Ideal 2 The D peak width was calculated by dividing the loading time by the flow rate ratio. 2Deviation of D peak width from ideal injection width vs. flow rate ratio ( Figure 6B ) and loading time ( Fig.6D ) Fig. 6A and Figure 6B In the example, the loading time is fixed at 0.25s. 2 D The flow rate was changed from 4 mL / min to 40 mL / min. Figure 6C and Fig.6D middle, 2 The flow rate was fixed at 16 mL / min and the loading time was varied from 0.1 s to 0.5 s. 1 D flow rate = 1.2 mL / min, modulation time = 2 s. Error bars were obtained from 3 measurements.

[0050] 7A to 7E . Fig. 7A A 0.5m 2 Schematic diagram of FRPM of Dμ columns (microcolumns). Figure 7B A depiction based on a photograph of an integrated FRPM chip (top) with a backside heater (bottom) is shown. Figure 7C shows the C of the integrated FRPM chip using deactivated 6 , C 7 , C 8 , benzene and toluene 1 D Chromatogram and 2 D Chromatogram. Fig.7D Shows C 7 exist 1 D and 2 Enlarged view in D. Fig. 7E Shows C 7 exist 2 Enlarged view in D. Experimental conditions: loading time = 0.25 s; modulation time = 2 s; 1 D flow rate = 1.1 mL / min; 2 D Flow rate = 14 mL / min. 1 D Temperature ramp curve and Figure 2 The integrated chip is kept at an isothermal temperature (about 20°C). Helium is used as 1 D Both carrier gas and auxiliary flow.

[0051] FIG. 8A to FIG. 8B . Fig. 8A Schematic diagram of an integrated FRPM-based portable comprehensive 2D μGC device prepared according to certain aspects of the present disclosure. The integrated FRPM module contains 0.5 m long WAX 2 Dμ column. Figure 8BA photo-based description of the system is shown. The dimensions of the device are 28 cm x 23 cm x 13 cm (length x width x height) and weighs 2.4 kg (including helium cylinder). The reference numerals are as follows: 1. Integrated FRPM and 0.5 m WAX 2 Dμ column module (inside the dotted square); 2. 1 D 10mOV-1μ column; 3. Preconcentrator. 4. μPID array; 5. Printed circuit board and data acquisition card (protected by copper mesh); 6. Pump; 7. 3-port valve; 8. 2-port valve; 9. DC-DC converter; 10. 24V power supply; 11. Joystick switch connected to wall power outlet.

[0052] FIG. 9A to FIG. 9J . Fig.9A The portable integrated 2DμGC device is shown. 1 D and 2 The mixture of 40 VOCs obtained by DμPID 1 D Chromatogram and 2 D Chromatogram. FIG. 9B to FIG. 9C Shows Fig.9A A magnified area of ​​region #1. FIG. 9D to FIG. 9E Shows Fig.9A of 1 D and 2 Area #2 in D. Fig.9F shows a 2D contour plot using a new method that relies on Fig.9A In 1 D Chromatogram and 2 D chromatogram of both. Peaks 13 to 16 are magnified ( Figure 9G ), Peaks 31 to 32 ( Figure 9H ), Peaks 26 to 28( Fig.9I ) and Peak 36( Figure 9J ). Figure 9H and Figure 9J Corresponding to Fig. 9C and Fig.9E For comparison, FIG. 28A to FIG. 28C A 2D contour plot using a conventional method is given in 2 D micro PID data. Experimental conditions: 1 D flow rate = 1.2 mL / min; 2 D Flow rate = 11 mL / min. Loading time = 0.4 s; Modulation was segmented into three cycles: Modulation time = 1 s (from 0 to 75 s); 2 s (from 75 s to 180 s); and 4 s (from 180 s to 350 s). 1 Dμ column (OV-1) and 2 D Integrated FRPM Module Both of them experience temperature ramp ( Fig. 13B and FIG. 26A to FIG. 26D ). Helium is used as 1 D Both carrier gas and auxiliary flow.

[0053] FIG. 10A to FIG. 10F A method of manufacturing a FRPM according to certain aspects of the present disclosure is shown, including an integrated version with 2D pillar and μ pillar microfabrication processes. Fig. 10A In FIG. 5 , a soft mask of photoresist exposes both the pillars and the inlets / outlets. Fig. 10B An oxide hard mask created by deep-reactive-ion-etching (DRIE) is shown. Fig. 10C A soft mask exposing only the inlet / outlet of the DRIE to 150 μm is shown. Fig. 10D It is shown that DRIE is applied over the entire pattern area to etch inlets / outlets to 400 μm and pillars to 250 μm. Fig. 10E Buffered hydrofluoric acid (BHF) stripping of the oxide mask is shown, and anodic bonding with Pyrex glass to seal the post. Fig.10F A patterned metal heater (30nm titanium / 320nm platinum) deposition on the back side is shown.

[0054] FIG. 11A to FIG. 11B Shows that there is 2 Coating procedure of the integrated FRPM of the Dμ column. Fig.11A Step I is shown: Hexamethyldisilane (HMDS) deactivates all microfluidic channels. Fig. 11B Step II is shown: 2 Dμ column coating. Use dummy 10mμ column for coating flow control. Only selected channels are coated. After coating, the coating outlet is sealed by epoxy resin.

[0055] FIG. 12A to FIG. 12D It shows that in the absence of ( Fig. 12A , Fig. 12C ) and have ( Fig. 12B , Fig.12D ) In the comparative FRPM of the flow resistor prepared according to certain aspects of the present disclosure, the FRPM is 2 D. Velocity field distribution during the loading and separation stages.

[0056] FIG. 13A to FIG. 13B Shows Figure 2 Unmodulated operation of the system depicted in . Fig.13A Shows the use of Figure 2 A setup calibration 1 D and 2Unmodulated operation of DμPID. 1 D= 2 D = 1.2 mL / min flow rate. The results show that 2 The sensitivity of DμPID is 2 2.4 times of DμPID. Fig. 13B Shows 1 D 10m Temperature ramp plot of OV-1 coated micropillars.

[0057] FIG. 14A to FIG. 14C Shown by 1 DμPID detected C 6 , C 7 and C 8 of 1 D peak delay and flow rate ratio ( Fig.14A ), loading time( Fig. 14B ) and modulation time ( Fig. 14C ) relationship.

[0058] FIG. 15A to FIG. 15D . The C was amplified using the FRPM module 7 of 1 D Chromatogram and 2 D Chromatogram. 2 D flow rate = 14 mL / min ( Fig.15A )、25mL / min( Fig. 15B )、30.5mL / min( Fig. 15C ) and 37mL / min( Fig.15D ). For all experiments, 1 D Flow rate = 1.2 mL / min, loading time = 0.25 s, modulation time = 2 s. Black arrows indicate 1 Jitter in the D peak.

[0059] FIG. 16A to FIG. 16D . Fig.16A A schematic diagram of a microfabricated pneumatic modulator without a 40 μm width flow blocker is shown. The flow blocker region has the same 250 μm x 250 μm (width x depth) cross section as all other channels. FIG. 16B to FIG. 16D Shows C 7 Enlarged 1 D Chromatogram and 2 D Chromatogram. 2 D flow rate = 6mL / min ( Fig. 16B )、11mL / min( Fig. 16C ) and 20mL / min( Fig.16D ). For all experiments, 1 D Flow rate = 1.2 mL / min, loading time = 0.25 s, modulation time = 2 s. Black arrows indicate1 Jitter in the D peak.

[0060] FIG. 17A to FIG. 17C . Fig.17A The calculated retention time delay as a function of α is shown. Fig. 17B The retention time delay as a function of loading time is shown. α=0.8, modulation time=2. Fig. 17C The retention time delay is shown as a function of the modulation time. α = 0.8, loading time = 0.25 s. In all calculations, L = 10 m, V 0 =0.1m / s.

[0061] 18A to 18E shows the use of the FRPM module C 7 Enlarged 1 D Chromatogram and 2 D Chromatogram. Loading time = 0.1s ( Fig.18A )、0.2s( Fig.18B )、0.3s( Fig.18C )、0.4s( Fig.18D ) and 0.5s( Fig.18E ). For all experiments, modulation time = 1 s, 1 D flow rate = 1.2 mL / min, 2 D Flow rate = 16 mL / min.

[0062] FIG. 19A to FIG. 19B . Fig.19A Shows from 18A to 18E Extracted 2 D and 1 C in D 7 The peak area ratio between the peaks. Fig.19B Shown by Fig.19A The peak area ratios were normalized by the extracted loading times. Error bars were obtained from 3 measurements.

[0063] FIG. 20A to FIG. 20G shows the C running without flow blocker 7 Enlarged 1 D Chromatogram and 2 D chromatogram, where loading time = 0.025 s ( Fig. 20A )、0.05s( Fig. 20B )、0.1s( Fig. 20C )、0.2s( Fig.20D )、0.3s( Fig.20E )、0.4s( Fig.20F ) and 0.5s( Figure 20G ). For all experiments, modulation time = 1 s, 1 D flow rate = 1.3 mL / min,2 D flow rate = 7.5 mL / min. Black arrows indicate 1 Jitter characteristics in the D peak.

[0064] FIG. 21A to FIG. 21B . Fig.21A Shows from FIG. 20A to FIG. 20G Extracted 2 D and 1 C in D 7 The peak area ratio between the peaks. Fig.21B It is shown that from ( Fig.21A ) Peak area ratio normalized by the loading time extracted. Error bars were obtained by 3 measurements.

[0065] FIG. 22A to FIG. 22D An alternative FRPM prepared according to certain aspects of the present disclosure is shown, which has a single valve-based operating principle for comprehensive 2D μGC. Fig.22A Shows 1 D to 2 D loading configuration, where the normally-open (NO) port in a 3-port valve is open (typical 1 D flow rate: about 1 mL / min). C = common; NC = normally closed. The flow blocker (marked in orange) is a 1.2 m long guard column. The blue and green arrows indicate 1 D flow direction and auxiliary flow direction. Fig. 22B Shows the high 2 D flow (typical flow rate: about 10mL / min) with NC port open 2 D separation, achieving rapid 2 D injection and fast 2 D separation. Fig. 22C A schematic diagram of a single valve FRPM is shown. Figure 1 Compared to the illustrated FRPM embodiment, the single valve FRPM has an additional port 5 . Fig.22D A description based on a photograph of a single valve FRPM module with a 3-port valve is shown.

[0066] FIG. 23A to FIG. 23D . Fig.23A shows the setup used to characterize a single valve FRPM module (with Figure 5A same as the settings in ). Fig. 23B Shows C 6 , C 7 , C 8 , benzene and toluene 1 D Chromatogram and 2 D Chromatogram. Fig.23C It is C 7 exist 1D and 2 Enlarged view in D. Fig.23D It is C 7 exist 2 Enlarged view in D. Experimental conditions: loading time = 0.25 s; modulation time = 2 s; 1 D flow rate = 1.4 mL / min; 2 D flow rate = 18.5 mL / min. Before connecting to the single valve FRPM module, 1 End Calibration of DμPID 1 D flow rate. After connecting a single valve FRPM module and switching the 3-port valve to the normally closed port, 2 End Calibration of DμPID 2 D Flow rate. 1 The Dμ column undergoes a temperature ramp (see Fig. 13B ). The single valve FRPM is at room temperature (about 20°C). Helium is used as 1 D Carrier gas and auxiliary flows. Note that an external flow blocker (1.2 m guard column) was used to limit the buffer flow rate during loading, but could in principle be microfabricated on the same chip for compactness.

[0067] FIG. 24A to FIG. 24C . Fig.24A Shows 2 D peak width; Fig. 24B Shows 2 D Deviation of peak width from the ideal injection width; Fig.24C Shows C 6 , C 7 and C 8 of 1 D Relationship between peak delay and flow rate ratio for a system based on a single valve FRPM module. Experimental conditions: For all experiments, 2 D flow rate = 3 mL / min to 44 mL / min, 1 D flow rate = 1.4 mL / min, loading time = 0.25 s, modulation time = 2 s. Error bars were obtained from 3 measurements.

[0068] FIG. 25A to FIG. 25C . Fig.25A Shows from Figure 7C Extracted from 2 D peak width. Fig.25B Shows 2 D peak width and ideal 2 D Deviation of injection width. Fig.25C Shows C 6 , C 7 and C 8 of 1Relationship between D peak delay and flow rate ratio of the system based on the integrated FRPM module. Experimental conditions: For all experiments, 1 D flow rate = 1.1 mL / min, 2 D flow rate = 3.6 mL / min to 31 mL / min, loading time = 0.25 s, modulation time = 2 s. Error bars were obtained from 3 measurements.

[0069] FIG. 26A to FIG. 26D A portable integrated 2D μGC based on a FRPM module prepared according to certain aspects of the present disclosure is shown in FIG. 7 Enlarged 1 D Chromatogram and 2 D chromatogram, where 2 D flow rate = 9 mL / min ( Fig.26A )、14mL / min( Fig.26B )、20mL / min( Fig.26C ) and 25mL / min( Fig.26D ). For all experiments, 1 D flow rate = 1.1 mL / min, loading time = 0.25 s, modulation time = 2 s. The black arrow indicates when 2 When the flow rate is higher than 20 mL / min, 1 Jitter characteristics in the D peak.

[0070] Fig. 27 A temperature ramp graph of an integrated FRPM chip prepared according to certain aspects of the present disclosure is shown. 2 The D-pillar has the same temperature ramp profile.

[0071] FIG. 28A to FIG. 28C . Fig.28A It shows that only the 2 2D contour plot generated from D chromatogram. Fig.28B and Fig.28C Corresponding to Figure 9G and Fig.9I Magnified area of ​​. Note that from ( Fig.28A ) only counts 32 peaks in the 2D contour map, while Fig.9F 40 peaks were counted in the 2D contour plot.

[0072] Fig.29 Shows Fig.9A Middle C 9 The red arrow indicates 2 The separation in D implies 1 Co-elution in D.

[0073] FIG. 30A to FIG. 30D . Fig. 30A A schematic diagram of a comprehensive 2D μGC device based on FRPM prepared according to certain aspects of the present disclosure operating in a stopped-flow modulation mode in which port 4 is permanently blocked. When the 2-port valve is closed, 1 D separation, from 1 The eluate from column D was loaded onto 2 D column. When the 2-port valve is open, pause 1 D separation, helium source production for rapid 2 D Separation High 2 D flow. Fig. 30B The 40 VOCs generated by stopped flow modulation are shown. 1 D Chromatogram and 2 Chromatogram D. The inlet shows the concentration of two VOCs. 2 The entire separation was completed in about 600 seconds, much longer than Fig.9A 300s reported in . Fig. 30C Shows Fig. 30B The enlarged section shows 1 D Strong jitter in the chromatogram. Fig.30D Unmodulated operation is shown when the 2-port valve is permanently closed. Experimental conditions: 1 D flow rate = 1.2 mL / min, 2 D Flow rate = 11 mL / min, Loading time = 0.4 s, Modulation time = 2 s. Unmodulated: 1 D flow rate = 2 D flow rate = 1.2 mL / min. 1 Dμ column and 2 D integrated FRPM modules have undergone Fig. 13B and Fig. 27 Temperature ramp shown.

[0074] Corresponding reference numerals indicate corresponding parts throughout the several views of the drawings. DETAILED DESCRIPTION

[0075] Example embodiments are provided so that the present disclosure will be thorough and the scope will be fully conveyed to those skilled in the art. Many specific details, such as examples of specific compositions, components, devices, and methods are set forth to provide a thorough understanding of the embodiments of the present disclosure. It will be apparent to those skilled in the art that specific details need not be employed, that the example embodiments may be implemented in many different forms, and that these example embodiments should not be construed as limiting the scope of the present disclosure. In some example embodiments, well-known processes, well-known device structures, and well-known techniques are not described in detail.

[0076] The terms used herein are only for the purpose of describing specific example embodiments, and are not intended to be restrictive. As used herein, unless the context clearly indicates otherwise, the singular forms "one", "an" and "the" may be intended to also include plural forms. The terms "comprise", "include", "contain" and "have" are inclusive, and therefore specify the presence of the features, elements, compositions, steps, integers, operations, and / or parts, but do not exclude the presence or increase of one or more other features, integers, steps, operations, elements, parts and / or their groups. Although the open term "comprising" should be understood as a non-limiting term for describing and claiming the various embodiments set forth herein, in some respects, the term may alternatively be understood as a more restrictive and constrained term, such as "consisting of" or "consisting essentially of". Thus, for any given embodiment that references compositions, materials, components, elements, features, integers, operations, and / or process steps, the present disclosure also specifically includes embodiments that consist of, or consist essentially of, such referenced compositions, materials, components, elements, features, integers, operations, and / or process steps. In the case of "consisting of," alternative embodiments do not include any additional compositions, materials, components, elements, features, integers, operations, and / or process steps, while in the case of "consisting essentially of," any additional compositions, materials, components, elements, features, integers, operations, and / or process steps that materially affect the basic and novel characteristics are excluded from such embodiments, but any compositions, materials, components, elements, features, integers, operations, and / or process steps that do not materially affect the basic and novel characteristics may be included in such embodiments.

[0077] Any method steps, processes, and operations described herein should not be construed as necessarily being performed in the particular order discussed or illustrated, unless expressly specified as an order of performance. It should also be understood that additional or alternative steps may be employed unless otherwise indicated.

[0078] When a component, element or layer is referred to as being "on another component or layer," "engaged to another component or layer," "connected to another component or layer," or "coupled to another component or layer," the component, element or layer may be directly on another component, element or layer, directly engaged, connected or coupled to another component, element or layer, or there may be intermediate elements or layers. Conversely, when an element is referred to as being "directly on another component or layer," "directly engaged to another component or layer," "directly connected to another component or layer," or "directly coupled to another component or layer," there may be no intermediate elements or layers. Other words used to describe the relationship between elements should be interpreted in a similar manner (e.g., "between" versus "directly between," "adjacent" versus "directly adjacent," etc.). As used herein, the term "and / or" includes any and all combinations of one or more of the associated listed items.

[0079] Although the terms first, second, third, etc. can be used herein to describe various steps, elements, components, regions, layers and / or sections, unless otherwise indicated, these steps, elements, components, regions, layers and / or sections should not be limited by these terms. These terms can only be used to distinguish a step, element, component, region, layer and / or section from another step, element, component, region, layer and / or section. When used in this article, unless the context clearly indicates, terms such as "first", "second" and other numerical items do not imply order or sequence. Therefore, without departing from the teaching of the exemplary embodiment, the first step, the first element, the first component, the first area, the first layer or the first section discussed below can be referred to as the second step, the second element, the second component, the second area, the second layer or the second section.

[0080] Spatially or temporally relative terms (e.g., "before," "after," "inside," "outside," "under," "below," "below," "above," "over," etc.) may be used herein to simplify the description of the relationship of one element or feature to another element or features as shown in the drawings. Spatially or temporally relative terms may also be intended to encompass different orientations of the device or system in use or operation in addition to the orientation depicted in the drawings.

[0081] Throughout this disclosure, numerical values ​​represent approximate measurements or limits of ranges to encompass minor deviations from given values ​​and embodiments with values ​​that are approximately mentioned and embodiments with values ​​that are exactly mentioned. Except in the working examples provided at the end of the detailed description, all numerical values ​​of parameters (e.g., quantities or conditions) in this specification (including the appended claims) should be understood in all cases as modified by the term "about", regardless of whether "about" actually appears before the numerical value. "About" means that the numerical value allows some slight imprecision (close to exact in value; approximately or reasonably close to the value; almost). If the imprecision provided by "about" is not understood in this ordinary sense in the art, "about" as used herein at least represents the variation that can be caused by the ordinary methods of measuring and using these parameters. For example, "about" can include the following variations: less than or equal to 5%, optionally less than or equal to 4%, optionally less than or equal to 3%, optionally less than or equal to 2%, optionally less than or equal to 1%, optionally less than or equal to 0.5%, and in some aspects, optionally less than or equal to 0.1%.

[0082] Additionally, disclosure of ranges includes disclosure of all values ​​within the entire range and further divided ranges, including endpoints and sub-ranges given for such ranges.

[0083] Example embodiments will now be described more fully with reference to the accompanying drawings.

[0084] In various aspects, the present disclosure provides a flow limiting pneumatic modulator (FRPM) assembly for a multidimensional gas chromatography system. Such a FRPM assembly can be a microfabricated chip-based FRPM that is capable of performing a first dimension ( 1 D) column separation, rapid injection into the second dimension of the multidimensional gas chromatography system ( 2 D) column, and achieve a high second dimension ( 2 D) Column flow rate. In the FRPM assembly provided, a novel pneumatic modulator is provided for cutting the eluate from the first dimension column and then injecting them into the second dimension column. In some aspects, the multidimensional gas chromatography system has a first chromatographic column and a second chromatographic column, the first chromatographic column is a first micro gas chromatography column, and the second chromatographic column is a second micro gas chromatography column, wherein the multidimensional gas chromatography device is portable. The term "microfluidic channel" may include one or more fluid flow paths having a size of tens of microns to hundreds of microns. As used herein, the term "fluid" is intended to broadly encompass gases, liquids, vapors, semi-liquids, and solid suspensions in liquids or gases.

[0085] Figure 1The multidimensional gas chromatography system 40 shown includes a FRPM assembly, or more particularly includes a flow-restricted pneumatic modulator (FRPM) assembly 50 depicted by a dashed box. The FRPM assembly 50 includes a first y-shaped fluid connector 60, generally depicted by dashed lines, having an inlet 62, a first channel 64 having a first outlet 66, and a second channel 68 having a second outlet 70, the inlet, the first channel, and the second channel are all in fluid communication with each other. The inlet 62 is configured to be connected to a first chromatographic column 80 upstream of the FRPM assembly 50, and is therefore in fluid communication with the first chromatographic column 80. The first chromatographic column 80 receives a sample fluid, which includes one or more target analytes to be analyzed and detected in the multidimensional gas chromatography system 40. The second outlet 70 is configured to be connected to a waste line or bypass line 84 downstream.

[0086] Thus, in this variation, the FRPM assembly 50 may include a 1×2 first y-shaped connector 60 that connects the first dimensional column 80 and the two downstream first and second channels 64 and 68 (at Figure 1 FRPM assembly 50 also includes a second y-shaped fluid connector 72 generally depicted by dashed lines, as will be further described below.

[0087] The FRPM assembly 50 also includes a first flow blocker component 96 disposed in the first channel or upper channel 64 of the y-shaped connector 60. The first flow blocker component 96 can be a short channel or column, but has a much smaller cross-section than other fluid channels in the FRPM assembly 50. The second channel or lower channel 68 can have a second flow resistance to convection that is less than the first flow resistance associated with the first flow blocker component 96. In certain variations, the FRPM assembly 50 may also optionally include a second flow blocker component 98 ("flow blocker 2") disposed in the second channel or lower channel 68. The flow resistance of "flow blocker 1" 96 is much greater than that of "flow blocker 2" 98, and therefore provides an asymmetric flow resistance for the flow-limiting pneumatic modulator 50.

[0088] The FRPM assembly 50 also includes a second y-shaped fluid connector 72, which is generally depicted by a dotted line, and has a second inlet 74, a third inlet 76, a third channel 78, and a third outlet 79, and the second inlet, the third inlet, the third channel, and the third outlet are all fluidly connected to each other. The second y-shaped fluid connector 72 is therefore positioned in an orientation opposite to the first y-shaped fluid connector 60, so that the first y-shaped fluid connector 60 has a single inlet (first inlet 62) and two outlets (first outlet 66 and second outlet 70), and the second y-shaped fluid connector 72 has two inlets (second inlet 74 and third inlet 76) and a single outlet (third outlet 79) in the flow direction of the flow from the first chromatographic column 80 and toward the second chromatographic column 82 or the bypass line 84. The first outlet 66 of the first y-shaped fluid connector 60 is therefore connected to the second inlet 74 of the second y-shaped fluid connector 72 and is fluidly connected to the second inlet 74. Therefore, the second inlet 74 is fluidly connected to the first outlet 66 of the first y-shaped connector 60, and is configured to receive the flow from the first chromatographic column 80.

[0089] The multidimensional gas chromatography system 40 may also include an auxiliary flow conduit 100 located upstream of the FRPM assembly 50, which receives an inert carrier gas / auxiliary fluid. The third inlet 76 is configured to be in fluid communication with the auxiliary flow conduit 100 so that the auxiliary fluid can pass through the second y-shaped fluid connector 72. Any fluid flow passing through the second y-shaped fluid connector 72 exits through the third channel 78 and the third outlet 79 and is directed toward the second chromatographic column 82.

[0090] The FRPM assembly 50 includes at least one flow control valve. For example, Figure 1 The FRPM assembly 50 in the embodiment has a first flow control valve 90 located upstream of the second inlet 76 of the second y-shaped fluid connector 72, and the first flow control valve controls the flow of auxiliary fluid into the second y-shaped fluid connector 72. A second flow control valve 92 is also included, which is fluidically connected to the second outlet 70 of the first y-shaped fluid connector 60 and is therefore located upstream of the second chromatographic column 82. In some variations, the first flow control valve 90 and the second flow control valve 92 are two-port valves each having an open position and a closed position. As will be further described herein, the FRPM assembly 50 is configured to operate as an injector and modulator for the second chromatographic column 82.

[0091] The second chromatography column 82 includes a detector 110 for detecting one or more target analytes processed within the second chromatography column 82. Figure 1 Not shown, but other detectors may be included in the system, including downstream of the first dimension chromatography column 80 to detect analytes eluting therefrom.

[0092] The detector can be a photoionization detector (PID), such as a micro-photoionization detector (μPID). In some variations, the detector can be a non-destructive on-column detector, such as a capillary based optical ring resonator (CBORR) device, a sensor based on a Fabry-Perot interferometer, a chemi-resistor sensor, an acoustic wave sensor, a thermal conductivity sensor, etc.

[0093] In addition, the multidimensional gas chromatography system 40 may have additional components known in the art but not shown, including preconcentrators, additional columns, seals, valves, monitors (e.g., pressure monitors and temperature monitors), connectors, electrical wiring, gaskets, controllers, etc.

[0094] In certain aspects, the present disclosure contemplates FRPM components and / or portions of a multidimensional gas chromatography device formed in a substrate such as a chip, a plate, or a base platform. As non-limiting examples, the substrate may be inorganic or organic, such as silica, silicon, glass, a polymer, and the like. In certain variations, the multidimensional gas chromatography device includes a substrate in which a FRPM component is formed and one of the following configurations: (i) a first chromatographic column upstream of the FRPM component; (ii) a second chromatographic column downstream of the FRPM component; or (iii) a first chromatographic column upstream of the FRPM component and a second chromatographic column downstream of the FRPM component. In this manner, the FRPM and the chromatographic columns may be microfluidic structures, and the multidimensional gas chromatography may be portable.

[0095] like FIG. 4A to FIG. 4B As best shown in FIG. 1 , the flow-restricted pneumatic modulator (FRPM) assembly 50 may have Figure 4A , in which both the first fluid flow control valve 90 and the second fluid flow control valve 92 are closed. When the first flow control valve 90 and the second flow control valve 92 are closed, the first chromatographic column ( Figure 1 The fluid sample / flow 120 eluted from the second chromatographic column ( 80 ) is directed through the first channel 64 and the first outlet 66, and through the first flow blocker component 96 of the first y-shaped fluid connector 60, into the second inlet 74 of the second y-shaped fluid connector 72, and out of the third outlet 79. Therefore, in the first operating mode, the fluid sample 120 is directed to the second chromatographic column ( Figure 1 82) as shown in FIG.

[0096] like Figure 4B As shown, the flow restricting pneumatic modulator (FRPM) assembly 50 also has a second operating mode, in which the first fluid flow control valve 90 and the second fluid flow control valve 92 are open to guide the first chromatographic column ( Figure 1 80) eluted fluid sample 120 passes through the second channel 68 and the second outlet 70 of the first y-shaped fluid connector 60. In this second operating mode, the fluid sample 120 is directed to a waste line or a bypass line 84.

[0097] like Figure 4B As shown, the auxiliary fluid 130 (eg, carrier gas) originates from the auxiliary fluid conduit ( Figure 1 100), wherein the first flow control valve 90 is configured to receive an auxiliary fluid 130. The auxiliary fluid 130 flows to the second chromatographic column ( Figure 1 82), through the first flow blocker component 96, the first channel 64, through the second channel 68, and out of the first outlet 70, where the auxiliary fluid 130 then passes through the opened second control valve 92 to the bypass line 84. Therefore, in the second operating mode, the auxiliary flow 130 travels through a portion of the first channel 64 to minimize or prevent the fluid flow 120 from flowing through the first channel 64 and thereby flowing backward through the second Y-shaped fluid connector 72 to the downstream second chromatography column ( Figure 1 82 shown in FIG. 8). Thus, the first flow blocker member 96 is used to minimize or prevent the fluid sample 120 from traveling in a direction toward the second y-shaped fluid connector 72 (and thereby entering the second y-shaped fluid connector 72) by using a very small amount of downward auxiliary fluid 130 flow. Figure 1 In other words, the first flow blocker component 96 minimizes or blocks excessive auxiliary fluid 130 from flowing downward toward the first channel 64. If the flow of auxiliary fluid 130 toward the first channel 64 is not minimized, the flow and separation process in the first dimension chromatographic column 80 will be undesirably disturbed or perturbed. In the second operating mode, in particular, a portion of the auxiliary fluid 130 flows into the second dimension column thereby.

[0098] Thus, in the first operating mode of the flow-limiting pneumatic modulator 50, when both the first flow control valve 90 and the second flow control valve 90 are closed, the flow and eluate from the first dimension column are diverted to the first channel or upper channel 64 and then enter the second dimension column. The fluid stream / flow experiences a high flow resistance, the total resistance including the resistance from the first dimension column, plus the resistance from the first flow resistor 96 and the resistance from the second dimension column. As a result, the flow rate of loading the eluate (fluid sample 120) from the first dimension column to the second dimension column is low.

[0099] However, in the second operating mode, where both the first flow control valve 90 and the second flow control valve 92 are open, there are two effects. First, the flow from the first dimension column is diverted to the second or lower channel 68 of the y-shaped fluid connector 60 because the auxiliary fluid flow 130 flows downward through the first or upper channel 64 and blocks the first dimension flow 120 and the eluate / fluid sample 120 from entering the upper or first channel 64. Second, the flow in the first dimension column experiences a low flow resistance, with the total resistance being only the first dimension column and the optional second flow blocker component (in the Figure 1 The second flow blocker member 98 is shown in FIG. FIG. 4A to FIG. 4B As a result, the flow rate in the first dimension column becomes higher.

[0100] Based on the working principles discussed above, a comprehensive 2D GC incorporating a flow-limiting pneumatic modulator (FRPM) assembly according to certain aspects of the present disclosure can be operated as follows. In a first operating mode, both the first flow control valve 90 and the second flow control valve 92 are closed for a first duration, also referred to as a loading time, which can be a short amount of time. In some aspects, the first duration is less than or equal to about 0.2 seconds, although other first durations are contemplated below. Then, in a second operating mode, both the first flow control valve 90 and the second flow control valve 92 are switched to open for a second duration. The second duration in the second operating mode is greater than the first duration in the first operating mode. The time or duration when both valves are open is a second duration, which is referred to as the second dimension separation time.

[0101] In this second mode of operation, as described above, the flow and eluate from the first dimension column enter the second channel 68 at the bottom of the first y-shaped fluid connector 60. This allows separation of analytes to occur in the first dimension column at a high flow rate (e.g., a volume flow rate of about 1 mL / min to about 2 mL / min). At the same time, a high auxiliary fluid flows at a very high flow rate (e.g., about 5 mL / min) as a carrier gas for separation of the second dimension column. The greater the carrier gas flow rate, the sharper the injection peak in the second dimension column. As further described below, the peak width squeezing ratio is approximately determined by the carrier gas flow rate and the loading flow rate for the second dimension column.

[0102] The sum of the first duration (loading time) and the second duration (separation time) is the modulation time. In one example, for example, the first duration or loading time can be about 0.2 seconds, and the second duration or separation time can be about 1.8 seconds. Thus, the modulation time is 2 seconds. In some aspects, the modulation time or total run time can be greater than or equal to about 0.005 seconds to less than or equal to about 50 seconds, optionally greater than or equal to about 0.2 seconds to less than or equal to about 50 seconds, and optionally greater than or equal to about 0.2 seconds to less than or equal to about 20 seconds. The run order can optionally be: 0.2 seconds, 1.8 seconds, 0.2 seconds, 1.8 seconds, or 2 seconds. In some variations, the loading time can be from greater than or equal to about 0.2 seconds to less than or equal to about 50 seconds, optionally greater than or equal to about 0.2 seconds to less than or equal to about 20 seconds, greater than or equal to about 0.2 seconds to less than or equal to about 2 seconds.

[0103] The ratio of the first duration to the modulation time is the duty cycle. In some aspects, the duty cycle of the method and multidimensional chromatography system using the limited flow pneumatic modulator can be greater than or equal to about 1% to less than or equal to about 100%, and in some aspects, optionally greater than or equal to about 10% to less than or equal to about 100%. In some aspects, the limited flow pneumatic modulator can have a duty cycle less than or equal to about 50%, wherein the duty cycle is the ratio of the time of loading the sample / eluate to the second chromatographic column to the modulation time. In some aspects, the duty cycle (e.g., the sample loading time relative to the modulation time) ranges from greater than or equal to about 1% to less than or equal to about 50%, and in some aspects, optionally greater than or equal to about 10% to less than or equal to about 50% (e.g., 0.2 seconds loading time in a 2-second modulation cycle to 1 second loading time in a 2-second modulation cycle). In addition, the duty cycle may change throughout the operation of the gas chromatography (GC) system. For example, the duty cycle can change from 10% of the first 100 seconds of the GC operation to 50% of the remaining time of the GC operation.

[0104] The maximum modulation time of the restrictive pneumatic modulator in the multidimensional chromatography system can be less than or equal to about 50 seconds. In some aspects, the first duration / loading time can be 0.01% of the modulation time to as high as 99.99%, and the second duration / separation time can be 99.99% of the modulation time to as low as 0.01%, so that the scope of the first duration can be greater than or equal to about 0.005 seconds to less than or equal to about 49.995 seconds, and the second duration can be greater than or equal to about 0.005 seconds to less than or equal to about 49.995 seconds. In addition, the modulation time may change in the operation of the entire GC system. For example, the modulation time can be increased from 2 seconds of the first 100 seconds of the GC operation to 4 seconds of the remaining time of the GC operation.

[0105] In one example, the first duration / loading time can be 20 seconds. This allows the flow and eluate from the first dimension column to be turned to the first channel 64 in the first y-shaped fluid connector 60, to the second inlet 74, to the third outlet 79 in the second y-shaped fluid connector 72 with a low flow rate (e.g., a volume flow rate of 0.5 mL / min). Therefore, the eluate from the first dimension column can be injected into the second dimension column with an injection peak width of about 0.2 s. Therefore, in some modifications, in the first operating mode, the second chromatographic column has an injection peak width less than or equal to about 0.2 seconds.

[0106] The injection peak width is determined by the first duration / loading time and the ratio of the first dimension flow rate (the flow rate in the first chromatographic column) to the second dimension flow rate (the flow rate in the second chromatographic column). For example, if the loading time is 0.2 s, the first dimension flow rate is 1 mL / min, and the second dimension flow rate is 10 mL / min, then the flow ratio is 10 (10 mL / min divided by 1 mL / min). The injection peak width is 0.2 s / 10 = 0.02 s. In some variations, the injection peak can be greater than or equal to about 0.001 seconds to less than or equal to about 10 seconds.

[0107] In some aspects, wherein the flow / fluid sample entering the second chromatographic column during the first operating mode has a first flow rate, and the auxiliary fluid entering the second chromatographic column during the second operating mode has a second flow rate. In some aspects, the ratio of the second flow rate to the first flow rate is greater than or equal to about 10:1. More specifically, the ratio between the carrier gas flow rate (5mL / min) and the loading flow rate (0.5mL / min) is 10. Therefore, when using 5mL / min of carrier gas, the peak width becomes 0.02s (excluding other peak broadening effects and peak narrowing effects such as analyte diffusion, analyte clogging compression, etc.). In the above embodiment, the injection peak width in the second chromatographic column is 0.2 seconds.

[0108] In various aspects, the method of the present disclosure further comprises repeatedly operating the restricted flow pneumatic modulator in the first operating mode for a first duration and operating the restricted flow pneumatic modulator in the second operating mode for a second duration. This may occur over a number of cycles.

[0109] In certain aspects, the net effect is that the eluate from the first dimension column can be periodically injected into the second dimension column at a 10% duty cycle (0.2 s divided by 2 s) with a certain modulation time (e.g., in the above example, 1.8 s + 0.2 s = 2 seconds). The first / injection flow rate is low (0.5 mL / min in the above example), while the auxiliary / carrier gas flow rate for the second dimension column is high (5 mL / min in the above example). The high ratio makes the injection peak width much sharper than the injection time (i.e., in the above example, a 0.2 injection time produces an injection peak width of 0.02 s).

[0110] In various aspects, the limited flow pneumatic modulator prepared according to the present disclosure can provide various advantages for a multi-dimensional gas chromatography system. First, due to the presence of the high flow resistance of the first flow blocker component 96, it provides a slow injection time (or loading time) from the first dimension column to the second dimension column. This makes the injection peak width sharper (determined by the ratio of the carrier gas flow rate to the loading flow rate for the second dimension column).

[0111] Second, a high auxiliary flow rate can be used to generate a very high carrier gas flow rate for the second dimension column without regard to the possibility that the high auxiliary flow may push analytes in the first dimension column backwards.

[0112] Third, it provides lower auxiliary flow consumption because most of the auxiliary flow is used as carrier gas for the second dimension column. Only a small part of the auxiliary flow flows downward through the first channel 64 (as described above in Figure 4B This portion of the flow is intended to prevent flow from the first dimension column from going to the first channel 64. The smaller this portion of the auxiliary flow is, the less the auxiliary flow is wasted, advantageously.

[0113] There is almost no need to stop in the first dimension separation. The effective flow rate is reduced from 1 mL / min (assuming that the first dimension flow to the lower channel is 1 mL / min) to (1 mL / min×90%+0.5 mL / min×10%=0.95 mL / min) (assuming that the loading flow rate for the second dimension column is 0.5 mL / min and the duty cycle is 10%). Therefore, the first dimension separation can be completed quickly.

[0114] In some variations, the length of the upper first channel 64 of the y-shaped fluid connector 60 is as short as possible. In some variations, the upper limit of the length can be estimated as the linear velocity of the flow (or analyte) in the upper first channel 64 multiplied by the loading time. For example, if the linear velocity of the flow (or analyte) is 5 cm / s and the loading time is 0.2s, the maximum length of the upper first channel 64 will be 5 cm / s×0.2s=1 cm. If the length of the upper first channel 64 is greater than the maximum length, then the eluate from the first dimension column will not have enough time to be completely transported to the second dimension column. Therefore, when the auxiliary flow is turned on, there will be a flow in the backward direction (i.e., from the upper first channel 64 to the lower second dimension column). Figure 1 "2 to "1" in the figure) pushes a portion of the eluate.

[0115] In one variation, Figure 2 Experimental setup and parameters are shown. In this example, a 3 cm long 0.1 mm inner diameter column (in the upper first channel) is used as the first flow blocker component. A 0.5 m long column is used as the second flow blocker component, which has the same flow resistance as the second dimension column with exactly the same size (length and inner diameter). When the first flow control valve and the second flow control valve are both opened, the flow rate in the first dimension column is about 1.8 mL / min. When the first flow control valve and the second flow control valve are both closed, the flow rate (i.e., loading flow rate) through the second dimension column is about 0.85 mL / min. The carrier gas for the second dimension column provided by the auxiliary flow when the first flow control valve is opened is 9 mL / min. Two detectors (detector 1 and detector 2) are used to monitor the eluate from the first dimension column and the second dimension column, respectively.

[0116] The results are FIG. 3A to FIG. 3D In 0.1s loading time ( Figure 3A ), the eluate from the first dimension column could not pass through the 3 cm long (inner diameter: 0.1 mm) column and reach the second dimension column. Therefore, no peak appeared in detector 2. However, when the loading time was increased to 0.2 s, 0.3 s, and 0.4 s, the eluate peak appeared in detector 2, which verified the operation of the FRPM assembly. The peak width on the second dimension column increased with the increase of the cutting time or the loading time. For example, for C 6 The peak width (full width at half maximum) of is 0.045 s, 0.051 s and 0.056 s in the case of loading times of 0.2 s, 0.3 s and 0.4 s.

[0117] In another experiment, the second dimension column was removed and the detector 2 was placed just behind the junction of the 3 cm (inner diameter: 0.1 mm) column and the auxiliary flow channel. This allowed the effect of the flow blocker to be tested without any interference from the second dimension column. 6 , C 7and C 8 Mixture. Loading time varied from 0.1s to 0.5s. At 0.1s loading time or cut time, no peak appeared in detector 2. When loading time was equal to or greater than 0.2s, a peak appeared in detector 2. 6 The peak width (full width at half maximum) of is 0.038 s, 0.042 s, 0.049 s and 0.057 s at loading time or cutting time of 0.2 s, 0.3 s, 0.4 s and 0.5 s, respectively. At a higher loading time (e.g., 0.5 s), the ratio between the loading time (0.5 s) and the peak width (0.057) is close to the ratio between the carrier gas flow rate (9 mL / min) and the loading flow rate (0.85 mL / min) because at a higher loading time, the peak broadening caused by the internal volume of the detector can be ignored (in the experiment, a photoionization detector with an internal volume of about 2.3 microliters was used, which corresponds to a scanning time of about 0.0023 mL / (9 mL / min)×60 s / min=0.015 s).

[0118] Obviously, the above-described FRPM assembly is not limited to use as an injector or modulator between a first dimension column and a second dimension column, and it can be used before any column (including the first dimension column).

[0119] The design, fabrication, and characterization of the FRPM assembly are further described herein. In certain aspects, in the absence of a first dimension ( 1 D) column perturbation, in the second dimension ( 2 D) Column / First Dimension ( 1 D) The injection peak width of about 25 milliseconds (ms) was achieved when the column flow rate ratio was greater than 10. Subsequently, the flow-limiting pneumatic modulator (also referred to herein as a microfabricated chip-based flow-limiting pneumatic modulator (FRPM)) was connected to a 0.5 m 2 Finally, a first-of-its-kind automated, integrated 2DμGC device was developed, which consists of a 10m OV-1 1 D microfabricated column (μ column) with built-in 0.5mWAX (i.e., polyethylene glycol (PEG)) 2 The integrated FRPM of the Dμ column and two flow-through micro-photoionization detectors (μPID) were used. The rapid separation of 40 volatile organic compounds (VOCs) within 5 minutes was also demonstrated. 1 D and 2 The end of the Dμ column is obtained using two μPIDs 1 D Chromatogram and 2 D chromatogram to construct a 2D contour plot, and only2 The use of a vapor detector at the end of the D column shows improved peak capacity compared to a conventional integrated 2D GC.

[0120] FIG. 4A to FIG. 4D A schematic block diagram of the FRPM and its operation is provided. The FRPM includes an inlet (port 1) for auxiliary flow, a 1 D eluate inlet (port 2), connected to 2 The outlet of the D column (port 3), the outlet for the waste line (port 4), and the 1 D and 2 Internal flow barrier between D. Auxiliary flow and waste line / bypass line are controlled by two 2-port valves. During loading in the first operating mode (Figure 4(A)), both valves are closed. 1 A portion of the D eluate is loaded onto the flow barrier component 2 D-pillar, as previously described above. In the second operating mode 2 During the D separation (Fig. 4(B)), both valves are open and high auxiliary flow is provided for 2 D Separated 2 D Carrier gas flow and prevention 1 D eluate enters 2 The buffer flow of the D column. At the same time, 1 D separation continues, and 1 D eluate is diverted to waste / bypass line. 2 After D separation, both valves close again and a new modulation cycle begins. FIG. 10A to FIG. 10F and FIG. 11A to FIG. 11B The fabrication of the FRPM is schematically shown.

[0121] The FRPM modulator assembly has several advantages over the conventional pneumatic modulators mentioned previously. First, high auxiliary flow rates can be used for rapid 2 D injection and fast 2 D separation. Secondly, the flow barrier restricts the auxiliary flow consumed in the waste line (see FIG. 12A to FIG. 12D ), which saves auxiliary flow. Third, also due to the flow blocker, the auxiliary flow is minimized 1 Therefore, a wide range of auxiliary flow rates and 1 D flow rate, without 1 D Flow disturbances (such as flow shocks during modulation switching and 1 D reflux). This allows 1 D Testing is performed immediately after exit to directly monitor 1D separation (discussed further below). In contrast, designs without flow barriers (e.g., conventional capillary flow technology) require careful 1 D and auxiliary flow balance, and may still experience flow fluctuations during modulation. 1 D exit to 2 The concentration (or density) of the eluate at the transfer junction at the inlet D is maintained. In contrast, Capillary Flow Technology relies on auxiliary flow to move the eluate from 1 D push to 2 D, thereby diluting the eluate concentration and reducing the 2 D signal. Fifth, 1 D separation is continuous (unlike stopped-flow modulation), which speeds up 1 D separated and reduced 1 D peak broadening. Sixth, the FRPM assembly prepared according to certain aspects of the present disclosure is multi-purpose and can be used by permanently closing the waste line valve and using 1 D and auxiliary flow share the same pressure / flow source to operate in stopped flow mode, as discussed further below. Seventh, FRPM components prepared according to certain aspects of the present disclosure can be easily microfabricated and can even be used with 2 The D-pillar is integrated on a single chip.

[0122] The dimensions of each FRPM chip are 8 mm × 5 mm × 1 mm (length × width × thickness). Figure 4(C) shows a schematic diagram of the microfluidic channels inside the FRPM, in which a 2 mm long, 40 μm × 170 μm (width × depth) channel is used as a built-in flow blocker component. The width and depth of the flow blocker component can be adjusted to achieve different flow resistances. All other channels have a cross-section of 250 μm × 250 μm. The FRPM module is constructed by connecting the FRPM chip to two 2-port valves at the corresponding ports (Figure 4(D)).

[0123] FIG. 12A to FIG. 12D Computational fluid dynamics (CFD, COMSOL) is shown for a FRPM with a flow resistor and a pneumatic modulator without a flow resistor (ie, the 40 μm wide channel is replaced with a 250 μm wide channel). ) Results. The entire simulation geometry consists of a 10 m 250 μm wide column (not shown) attached to a FRPM module. The geometry of the FRPM is similar to Figure 1 and FIG. 16A to FIG. 16DThe geometry shown is the same (no flow blocker). A laminar flow model was used in the simulations where helium was used as the gas flow and silicon was used as the wall. An input pressure (2 psi) was assigned at the inlet of the 10 m column and an input pressure (0.55 psi for FPRM without flow blocker) was assigned at the inlet of port 1 in the FRPM module. Fig. 12A , Fig. 12C )), while for the FPRM with flow resistor, the input pressure is 0.4 psi ( Fig. 12B , Fig.12D ). A closed valve was simulated by dispensing a very large viscosity (ie, 10,000) simultaneously at the inlet (port 1) and a small portion of the waste line (port 4).

[0124] exist 2 During D loading, the velocity remains constant for FRPM without or with flow resistor ( Fig. 12A , Fig. 12B ), because the additional flow resistance caused by the narrow 40 μm channel of the FRPM is negligible compared with the upstream 10 m column. This is consistent with the experimental results ( Figure 2 ) are consistent. 2 During D separation, the FRPM without flow resistor requires a higher input pressure from port 1 (0.55 psi compared to 0.4 psi) so that the flow rate at port 3 remains the same as the FRPM with flow resistor (see Figure 3C , Figure 3D )same. Fig. 12C and Fig.12D The comparison between 2 During D separation, when using a FRPM with a flow blocker, the auxiliary flow from port 1 will divert more flow to 2 D (as 2D carrier gas). At the same time, 1 D flow is diverted to the waste line by buffer flow across the flow blocker, which prevents 1 D Flow into 2 D and allow to continue 1 D separated without noticeable interruption.

[0125] Example

[0126] Analytical standard grade hexane, heptane, octane, benzene, toluene, hexamethyldisilazane (HMDS), and the 40 VOCs listed in Table 1 were purchased from Sigma-Aldrich (St. Louis, MO).

[0127] Table 1 40 VOCs used in the comprehensive 2DμGC system

[0128]

[0129]

[0130] N-type silicon wafers (P / N 1095, 100 mm diameter, 500 μm thickness), P-type heavily doped silicon wafers (100 mm diameter, 0.001 Ω-cm to 0.005 Ω-cm, 400 μm thickness), and Borofloat 33 glass (P / N 517) were purchased from University Wafer. Carbopack B (P / N 20273) and X (P / N 10437-U) were purchased from Sigma-Aldrich. Table 2 provides additional accessory materials.

[0131] Table 2 Accessory materials for system components.

[0132]

[0133] All materials were used as received without further purification or modification. Helium (P / N 49615 He) at 99.5% purity was used as the carrier and auxiliary gas and was purchased from Leland Gas Technologies (South Plainfield, NJ).

[0134] Component Manufacturing

[0135] 10m 1 D micropillars (cross section: 200 μm × 250 μm, width × depth), independent FRPMs, and integrated FRPMs and 0.5 m 2 Dμ column is based on FIG. 10A to FIG. 10F The FRPM module / chip was microfabricated using the same process as the microcolumns (for details, see FIG. 10A to FIG. 10F ). The μ-pillar microfabrication process was first Fig. 10A In the process, a soft mask of photoresist is used to expose both the pillar and the inlet / outlet. Fig. 10B In , an oxide hard mask is created by deep reactive ion etching (DRIE). Fig. 10C In , a soft mask is created by exposing only the inlet / outlet of DRIE to 150μm. Fig. 10D In , DRIE was used on the entire pattern area, the inlets / outlets were etched to a depth of 400 μm, and the pillars were etched to a depth of 250 μm. Fig. 10E , using buffered hydrofluoric acid (BHF) to strip the oxide mask, and anodically bonding the BHF to the Pyrex glass to seal the pillars. Fig.10FIn the example, a patterned metal heater (30nm titanium / 320nm platinum) was deposited on the back side.

[0136] The standalone FRPM does not have a heater on the back side of the chip, but the integrated FRPM and 2 The Dμ columns are manufactured with a shared backside heater. The manufacturing efficiency of the standalone FRPM is greater than about 95% (132 chips per 4-inch wafer), the manufacturing efficiency of the integrated FRPM is greater than about 90% (12 chips per 4-inch wafer), and the manufacturing efficiency of the 10mμ column is greater than about 50% (2 chips per 4-inch wafer).

[0137] With 0.5m 2 Dμ column (cross section: 250μm×250μm) coating process integrated FRPM FIG. 11A to FIG. 11B Before coating, the HMDS was injected 8 times at 120 °C for 1 hour. 2 Both the Dμ column and the FRPM channel were inactivated. During inactivation, the coating outlet was blocked with a rubber septum. 2 During Dμ column coating, the outlet of FRPM was blocked, leaving only the coating outlet open to ensure that no coating solution flowed into the FRPM channel. A dummy 10 μm column was attached to the coating outlet as a flow blocker to control the coating flow rate. The FRPM was dynamically coated with PEG by injecting 15 μL of solution and pushing out at a speed of 5 cm / min. 2 Dμ column. PEG: 2% (w / w) CarboWAX 20M dichloromethane solution, azobisisobutyronitrile (1% relative to CarboWAX) as crosslinker. Repeat 2 times for coating.

[0138] The column was subsequently treated with HMDS after each coating and then baked at 180°C for 1 hour before use. Finally, the guard column attached to the coating outlet was removed and HYSOL TM The outlets were plugged with epoxy resin. The same coating procedure was followed for the 10 mμ column using a 3% (w / w) solution of OV-1 in dichloromethane. The resistance of the integrated heater was measured to be 40 Ω for the integrated FRPM chip and 28 Ω for the 10 mμ column. Both columns were wire bonded to the PCB board to allow pulse width modulated heating using a peak voltage of 24 V. The μPID chip was fabricated as described in our previous work. The μPID array was packaged on a PCB board as Figure 8B shown.

[0139] The stainless steel pre-concentrator is made by first cutting a 21.5 gauge stainless steel tube into 3.5 cm lengths. One end is first plugged with glass wool. Subsequently, the tube is filled with 0.75 mg of Carbopack B, then with 0.75 mg of Carbopack X, and then the other end is plugged with glass wool again. After loading, two universal compression connectors are attached to both ends of the stainless steel tube and secured using Hysol epoxy resin. A very thin layer (about 0.2 mm) of epoxy resin is also applied to the outer surface of the stainless steel tube body. The entire pre-concentrator is placed in an oven at 120°C and dried for 12 hours. Finally, the KAPTON TM The tape is wrapped around the stainless steel tube and then wrapped around a 32 gauge nickel-chromium heating wire (resistance is approximately 7Ω) to ensure electrical insulation between the stainless steel tube and the heating wire.

[0140] Comprehensive 2DμGC system setup and operation

[0141] Comprehensive 2DμGC system including stainless steel preconcentrator, 10m OV-1 coated 1 Dμ column, integrated FRPM and 0.5m 2 DWAXμ column, and 1 D and 2 Two flow-through μPIDs at the ends of D. Universal pressure-tight connectors and deactivated fused silica capillaries were used to interconnect the components. Figure 8B A detailed schematic diagram and equipment depiction are shown in . With both valves closed, 2 End calibration of DμPID (port 3) 1 D flow rate. 2 The end of the DμPID is calibrated by opening the two valves at the auxiliary flow inlet (port 1) and the waste line (port 4) 2 D flow rate. Analytes are stored in TEDLAR TM bag, and inject the sample into the backflush 1 The sample is then transferred to the preconcentrator before the Dμ column. During the run, the analytes are 1 D column separation, flow through 1 DμPID and then into the FRPM module for 2D comprehensive modulation and separation. Separation is performed in two dimensions using temperature ramp programming via an integrated backside heater. Helium (99.5% pure) is used as carrier and auxiliary gas. Loading and modulation times are set by simultaneously controlling the open (ON) and closed (OFF) states of the valves at the auxiliary flow inlet (port 3) and the waste line (port 4).

[0142] Segment-wise modulation was achieved by assigning different loading and modulation times to different analysis segments. The modulation times used in the present work were 1 s (from 0 to 75 s), 2 s (from 75 s to 180 s), and 3 s (from 180 s to 350 s). The loading time was kept constant at 0.4 s during all segments. The portable μGC runs on LabVIEW developed in-house. TM Software controlled.

[0143] 2D chromatogram construction

[0144] FIG. 28A to FIG. 28C The 2D contour plots in the figure use the traditional method adopted in conventional comprehensive 2D GC, which only has 2 A detector at the outlet of the D-pillar (i.e., 1 There are no detectors at the ends of the D columns). These 2D contour plots are generated by 2D interpolation of the original 2D GC data based on cubic splines. The interpolated value at a query grid point is based on a cubic interpolation of the values ​​at the adjacent grid points in each corresponding dimension.

[0145] FIG. 9F to FIG. 9J The 2D contour plot in 1 DμPID and 2 DμPID and DμPID get the signal. First use 2 The DGC data is interpolated using a traditional cubic spline method. 1 D GC data pair 1 The contour data along the D direction are corrected while retaining the 2 Peak shape in the D direction.

[0146] like Figure 5A As shown, using the FRPM module 2 The characteristic of D injection is that only 10m OV-1 1 D microcolumns and 2 20cm protective column in D (without 2 D separation column). Just before and after the FRPM, two flow-through μPIDs were used to measure and compare the eluate. Fig.14A Initial characterization was performed using the chromatograms in 1 D The eluate is transferred to 2 D, where 1 D and 2 There are slight delays between the eluting peaks detected by DμPID, which increase for heavier compounds. These delays are due to 2 Caused by the 20cm guard column in D. 6 and C 7 Comparison of peak heights shows that2 The sensitivity of DμPID is about 1 The sensitivity of DμPID is 2.4 times that of DμPID. 1 Compared with D, 2 The relative peak heights of other compounds in DμPID were reduced.

[0147] Next, the modulation operation was studied. FIG. 5B to FIG. 5D The use of alkanes and aromatics is shown 1 D chromatogram and modulation 2 Example of chromatogram D. Due to the rapid 2 D injection is important for maximizing 2 D peak capacity is important, so the 2 D and 1 The flow rate ratio between D 2 D / 1 D) is the function of C 6 , C 7 and C 8 of 2 D injection peak width (defined as the full width at half maximum) ( Fig. 6A ). Generally, the injection peak width varies with 2 D / 1 However, the measured injection peak width is always wider than the ideal peak width (which is defined as the loading time divided by the flow rate ratio). 2 D / 1 D flow rate ratio). This broadening is caused by the 20 cm guard column, and the relationship between the broadening and the flow rate can be seen in the Golay plot of the column ( Figure 6B ) can be seen. 2 D injection peak width is also affected by loading time and Figure 6C The peak widths measured increased linearly with increasing loading time and were again broader than the theoretical values. The broadening effect decreased with increasing loading time ( Fig.6D ), because it becomes less dominant due to the widening of the guard column. FIG. 14A to FIG. 21B As further described in , we explored the possibility of using 1 D flow and peak height (and peak area) are the maximum allowable 2 D / 1 D flow ratio, and a comparison between modulators with and without flow barriers. On this basis, injection peaks of approximately 25 ms can be achieved with a loading time of 0.25 s and a flow rate ratio greater than 10 without interfering 1 D flow or significant slowdown 1D separation.

[0148] FIG. 13A to FIG. 21B Provided are the maximum allowable values ​​of FRPM prepared according to certain aspects of the present disclosure for different loading times. 2 D / 1 D Additional characterization in terms of flow ratio and peak height (and peak area), and comparison between modulators with and without flow resistors.

[0149] As mentioned above, in order to produce rapid 2 D injection peak and acceleration 2 D separation, a higher flow rate ratio is desired. However, in the case of an excessively large flow rate ratio (i.e., a strong auxiliary flow), 1 D flow will slow down or even push back, resulting in 1 DμPID measured 1 D retention time delay (see FIG. 14A to FIG. 1 4D) and 1 D Jitter in the chromatogram (see FIG. 15A to FIG. 15D ). Delays in retention time increase analysis time, reduce peak capacity, and jitter makes it almost impossible to achieve 1 D Chromatographic analysis (e.g., peak fitting and apex identification). The flow barriers (i.e., narrow channels) in the FRPM significantly mitigate the 1 D preserves time delay and jitter.

[0150] FIG. 14A to FIG. 14C Shown by 1 DμPID detected C 6 , C 7 and C 8 of 1 D peak delay and flow rate ratio ( Fig.14A ), loading time( Fig. 14B ) and modulation time ( Fig. 14C ) relationship. Experimental conditions: ( Fig.14A )and( Fig. 14C )Loading time = 0.25s. Fig. 14B Loading time = 0.1s to 0.5s. Fig.14A and Fig. 14B Modulation time = 2s. Fig. 14C Modulation time = 1s to 4s. Fig.14A 2 D Flow rate = 4 mL / min to 40 mL / min. Fig. 14B and Fig. 14C of 2 D flow rate = 16 mL / min. For all experiments, 1 D flow rate = 1.2 mL / min. Error bars were obtained by 3 measurements. Results and FIG. 17A to FIG. 17C The theoretical calculation results shown are qualitatively consistent.

[0151] according to FIG. 14A to FIG. 14C , compared with the unmodulated case, it is observed 1 There is no significant delay in the retention time of the D eluting species. For example, in the modulated run (flow rate ratio of 20) and the unmodulated run (see Fig.13A ) 7 of 1 D retention time is 120s and 100s respectively. In addition, according to FIG. 15A to FIG. 15D , even at a flow rate ratio of 17( 2 D flow rate = 20mL / min), 1 D chromatogram still appears good and smooth. When the flow rate ratio is higher than 20 ( 2 In contrast, when the modulator was operated without a 40 μm wide flow barrier (i.e., the channel width of the flow barrier was changed to 250 μm instead of 40 μm, see Fig.16A ),not only 1 D retention time is significantly delayed (for example, at the same flow rate ratio of 20, C 7 The retention time becomes 145s), but at low flow rate ratios (e.g. 2 When the flow rate D is 11 mL / min, the low flow rate ratio is 9). 1 The D peak is strongly perturbed (see FIG. 16C to FIG. 16D ).

[0152] FIG. 15A to FIG. 15D shows the use of the FRPM module C 7 Enlarged 1 D Chromatogram and 2 D Chromatogram. 2 D flow rate = 14 mL / min ( Fig.15A )、25mL / min( Fig. 15B )、30.5mL / min( Fig. 15C ) and 37mL / min( Fig.15D ). For all experiments, 1 D Flow rate = 1.2 mL / min, loading time = 0.25 s, modulation time = 2 s. Black arrows indicate 1 Jitter in the D peak.

[0153] Fig.16ASchematic diagram of a microfabricated pneumatic modulator without a 40 μm width flow resistor is shown. The flow resistor region has the same cross section of 250 μm x 250 μm (width x depth) as all other channels. FIG. 16B to FIG. 16D Shows C 7 Enlarged 1 D Chromatogram and 2 D Chromatogram. 2 D flow rate = 6mL / min ( Fig. 16B )、11mL / min( Fig. 16C ) and 20mL / min( Fig.16D ). For all experiments, 1 D Flow rate = 1.2 mL / min, loading time = 0.25 s, modulation time = 2 s. Black arrows indicate 1 Jitter in the D peak.

[0154] To better understand 1 The delay of retention time D is first assumed during unmodulated operation (i.e., Figure 1 Both valves in A are closed) 1 The velocity of the analyte in column D is V 0 , which is also the rate at which analyte flows from the 1 D transfer to 2 D time 1 Analyte velocity in column D. 2 During the D separation phase, when both valves are open, a high assist flow is provided. 1 The velocity of the analyte in column D is reduced to αV 0 , where α ranges from 0 to 1. If we further assume that the modulation time is t and the duty cycle (ratio of loading time to modulation time) is m, then 1 The effective velocity of the analyte in column D is

[0155] V eff =V 0 ×m+αV 0 ×(1-m) (1)

[0156] The retention time of the analyte is

[0157]

[0158] There are several cases that can be studied. 1. Unmodulated operation. In this case, m = 1 and the analyte 1 D retention time is T = L / V 0 2. Stop the flow run. In this case, α = 0, and m ranges from 0 to 1. Therefore, the ID retention time becomes T = L / (mV 0), and is significantly delayed compared to unmodulated operation. For example, when m = 0.25, 1 D retention time was extended by 4 times. 3. Modulation operation was performed using our pneumatic modulator. FIG. 17A to FIG. 17C middle, 1 The D retention time delay is plotted for different values ​​of α (i.e., different flow rate ratios), loading time, and modulation time. In all calculations below, L = 10 m, V 0 =0.1m / s is fixed.

[0159] exist Fig.17A The retention time delay is calculated by formula (2) as a function of α. Higher values ​​of α correspond to smaller flow rate ratios. Loading time = 0.25 s, modulation time = 2 s, m = 0.125. Fig. 17B In , the retention time delay is a function of the loading time. α = 0.8, modulation time = 2. Fig. 17C In the above calculations, the time delay is kept as a function of the modulation time. α = 0.8, loading time = 0.25 s. In all calculations, L = 10 m, V 0 =0.1m / s.

[0160] exist 18A to 18E and FIG. 19A to FIG. 19B In the , the peak areas (and heights) for different loading times were examined, since the loading time determines the peak height from 1 D to 2 The amount of mass transferred by D. FIG. 17A to FIG. 17C It shows that when the loading time is 0.1, 2 Only a small peak appears in D. However, when the loading time is above 0.2 s, the peak height increases significantly. 1 D to 2 The loading time of D varies, so the same analyte peak is used 1 The corresponding entire 2 D peak area (for a given 1 D peak, there are multiple 2 D peak) to estimate the total mass transfer. As expected, Fig.19A Shows 2 The D peak area increases linearly with the loading time. 2 The peak area of ​​D is given by the corresponding 1 D Peak area normalization. Fig.19B According to the loading time 2The D peak area was further normalized. It was found that the loading time has a threshold of about 0.2 s, above which the mass transfer is almost the same regardless of the loading time. However, below 0.2 s, the mass transfer is significantly reduced. This threshold behavior can be attributed to the re-establishment of pressure to push the two 2-port valves when they switch from open to closed. 1 D The minimum time required for the eluate to pass through the narrow channel flow blocker. Similar threshold behavior was also observed for the pneumatic modulator without a 40 μm wide flow blocker (see FIG. 20A to FIG. 20G and FIG. 21A to FIG. 21B ). The threshold is lowered to about 0.05s, because it is easier (and faster) to re-establish pressure to push 1 The D eluate passes through a wider (250 μm) channel.

[0161] Note that pneumatic modulator chips with flow resistors varying in width from 20 μm to 250 μm were also fabricated and tested. 1 D peak distortion and significant 1 D retention time delay) the maximum allowed 2 D / 1 D flow rate ratio and 2 D provides the best performance in terms of injection width.

[0162] 18A to 18E shows the use of the FRPM module C 7 Enlarged 1 D Chromatogram and 2 D Chromatogram. Loading time = 0.1s ( Fig.18A )、0.2s( Fig.18B )、0.3s( Fig.18C )、0.4s( Fig.18D ) and 0.5s( Fig.18E ). For all experiments, modulation time = 1 s, 1 D flow rate = 1.2 mL / min, and 2 D Flow rate = 16 mL / min.

[0163] Fig.19A Shows from 18A to 18E Extracted 2 D and 1 C in D 7 The peak area ratio between the peaks. Fig.19B It is shown that from ( Fig.19A ) Peak area ratio normalized by the loading time extracted. Error bars were obtained by 3 measurements.

[0164] FIG. 20A to FIG. 20G shows the C running without flow blocker 7Enlarged 1 D Chromatogram and 2 D chromatogram, where loading time = 0.025 s ( Fig. 20A )、0.05s( Fig. 20B )、0.1s( Fig. 20C )、0.2s( Fig.20D )、0.3s( Fig.20E )、0.4s( Fig.20F ) and 0.5s( Figure 20G ). For all experiments, modulation time = 1 s, 1 D flow rate = 1.3 mL / min, and 2 D flow rate = 7.5 mL / min. Black arrows indicate 1 Jitter characteristics in the D peak.

[0165] Fig.21A Shows from FIG. 20A to FIG. 20G Extracted 2 D and 1 C in D 7 The peak area ratio between the peaks. Fig.21B Shown by Fig.21A The peak area ratios were normalized by the extracted loading times. Error bars were obtained from 3 measurements.

[0166] In another variation, an alternative FRPM module design prepared according to certain aspects of the present disclosure replaces the two 2-way 2-port valves with a single 3-way / 3-port valve ( FIG. 22A to FIG. 22C ).exist 2 During D loading and decoupling, the 3-port valve directs auxiliary fluid to the normally open and normally closed ports, respectively, allowing for integration with two valve modules ( FIG. 23A to FIG. 23D and FIG. 24A to FIG. 24C ) similar performance. The single valve FRPM module uses fewer parts than the two valve configuration, so it is less expensive and easier to maintain. However, due to the 1 D eluate adds additional buffer flow, so from 1 D exit to 2 The eluate concentration (or density) at the transfer junction at the D inlet is slightly reduced.

[0167] Integrated FRPM and 2 D Microcolumn Module

[0168] To further reduce equipment footprint and number of interconnections, FRPM with 0.5m 2 The Dμ pillars (cross section: 250 μm × 250 μm) are integrated on a single chip with dimensions of 18 mm × 15 mm × 1 mm (length × width × thickness) ( FIG. 7A to FIG. 7B ). Due to 0.5m 2The additional flow resistance of the Dμ column was re-evaluated for the integrated module using the same method as for the stand-alone module ( FIG. 25A to FIG. 25C and FIG. 26A to FIG. 26D ).like FIG. 7C to FIG. 7E As shown, when the flow rate ratio is 13, due to the additional 0.5 m microcolumn ( 2 The Dμ column is only deactivated without any stationary phase coating), and the integrated FRPM module shows the same performance as the additional 2 D peak broadening with similar performance to the standalone modules.

[0169] Automated, portable, comprehensive 2D μGC setup and operation

[0170] Automated portable comprehensive 2DμGC equipment ( FIG. 8A to FIG. 8B ) including 10m OV-1 1 Dμ column (non-polar), integrated FRPM and 0.5m WAX 2 Dμ column (polarity), respectively located at 1 D exit and 2 Two flow-through μPIDs for D outlets, and accessories (e.g., valves, preconcentrators, pumps, helium cylinders, and internal control software). Miniaturized comprehensive 2D GCs have previously been studied at the subsystem level using μ columns and thermal modulators / pneumatic modulators. However, these devices use desktop GC injectors and / or detectors and are therefore not automated stand-alone systems for field applications. In this variation, the present disclosure provides an automated, portable comprehensive 2D μGC without using any desktop components.

[0171] This integrated 2D μGC differs from traditional integrated 2D GC in several aspects. 2 DGC is only 2 A detector is used at the end of the D-pillar. 2 D detector information reconstruction 1 D chromatogram, which leads to 1 D retention time, 1 The error in D peak broadening and 1 In contrast, a comprehensive 2D μGC according to certain aspects of the present disclosure uses two flow-through μPIDs to monitor 1 D and 2 D eluate. This arrangement eliminates the need for reconstitution 1 D chromatogram is needed because 1 D Chromatogram can be directly obtained from 1 DμPID was obtained. As a result, the 1 D peak position (i.e., 1 D retention time), and retains the original 1D peak width, which improves separation performance (i.e., peak capacity). Second, due to the arrangement of two detectors, a new algorithm for generating 2D contour maps was developed to improve separation performance. Third, the modulation time was dynamically adjusted to accommodate different 1 D Peak Width. For example, shorter modulation times are used for earlier eluting species with sharper peak widths (which reduces the chance of undersampling), and longer modulation times are used for later eluting species.

[0172] exist FIG. 9A to FIG. 9J In a study conducted by the University of Wisconsin-Madison, 40 VOCs were separated in about 5 minutes using a comprehensive 2DμGC device. Fig.9A Shown are 1 DμPID and 2 DμPID obtained 1 D chromatogram and modulation 2 Chromatogram D. Two enlarged images are provided to visualize 2 Exemplary additional separations in D ( FIG. 9B to FIG. 9E ). Fig.9F shows the use of 1 D Chromatogram and 2 2D contour plot generated from the D chromatogram (described further below). FIG. 28A to FIG. 28C A 2D contour plot using the conventional method is drawn in 2 DμPID data. With the help of additional 1 D information, identifying more peaks in the same segment (e.g. Figure 9G and Fig.9I , which is different from conventional 2D contour plots (e.g. Fig.28B and Fig.28C As a result, all 40 VOCs were separated using the method of the present invention, compared to only 32 peaks using the conventional 2D contour method.

[0173] Due to the improved 1 D peak capacity and 1 The accuracy of D peak retention time was significantly improved by using these two detectors and the new method. 1 D. Construction of chromatogram. In order to evaluate 1 The increase of D peak capacity, benzene, C 7 , C 8 and C 9 of 1 D Retention times and peak widths were extracted from the conventional and new 2D contour plots and are listed in Table 3 .

[0174] Table 3: Benzene, C 7 , C 8 and C 9 of 1D retention time (RT) and full-width-at-half-maximum (FWHM) from conventional 2D contour plots (conventional, Fig.28A ) and a new 2D contour map (Fig. 6(F)) were reconstructed and directly from 1 D Chromatogram measurement (measurement) (Figure 6(A)). All values ​​are set in seconds.

[0175]

[0176]

[0177] * : Co-elution

[0178] The peak widths of all these analytes from the new 2D contour plots are sharper than those obtained from the conventional 2D contour plots, and their widths (and retention times) are very close to those obtained from the 1 D is the value directly measured by the chromatogram. It is worth noting that compared with the measured value, due to the 9 exist 1 D eluted in total, C 9 The peak width is narrower in the new reconstruction ( Fig.29 ). This shows that the algorithm can utilize 1 DData reconstructionC 9 The true peaks (i.e., non-coeluting peaks) of these analytes were calculated using the formula 1 D Peak Capacity:

[0179]

[0180] Among them, t 1 and t 2 is the retention time of two adjacent peaks, w 1 and w 2 is the corresponding peak width (full width at half maximum). s is the resolution. 1 D peak capacity n p_ New = 28 (R s =1) than conventional method n p_常规 = 20 showed significant improvement. In addition, 1 D. Accuracy of retention time. For example, C 7 The peak position is obtained by 1 The peak position reconstructed using an algorithm according to certain aspects of the present disclosure is 95 s, compared to 95.6 s using conventional methods.

[0181] Assuming isothermal separation, 2 The D peak capacity can be estimated as follows:

[0182]

[0183] Where N is the number of theoretical plates, t r The analyte 2 D retention time, t m is the dwell time. 9 (t r = 0.261 s, peak width = 0.055 s, reconstructed from the new 2D contour map) and a dwell time of 0.17 s, n p =2.2(R s =1). Therefore, the peak capacity of the entire system is 62. Note that FIG. 9A to FIG. 9J In this study, a comprehensive 2D μGC system was optimized to separate all 40 VOCs in a short time rather than to achieve high peak capacity.

[0184] In various aspects, the present disclosure provides a novel flow-restricted pneumatic modulator (FRPM) for 2D integrated gas chromatography (GC) that allows high auxiliary flow rates without interfering or interrupting 1 D flow, thus enabling rapid 2 D injection and separation, while maintaining 1 D separation and 1 D peak shape. In FRPM, the duty cycle (i.e., sample loading time versus modulation time) ranges from 10% to 50% (e.g., 0.2s to 1s loading time in a 2s modulation period), which is lower than other valve-based differential flow modulators that use duty cycles up to 80%. Although this low duty cycle does not affect the present 2D μGC system due to the use of a concentration-dependent vapor sensor (i.e., μPID), if 2 D detectors (e.g., flame ionization detectors) rely on mass flow rate, then 2 D signal (i.e., 2 D detector sensitivity) may be reduced.

[0185] The integrated FRPM was also used to build an automated, portable, comprehensive 2D μGC. A rapid separation of 40 different VOCs in about 5 minutes was demonstrated. A method for building 2D contour maps was developed that combines 1 D Chromatogram and 2 D chromatogram, compared with only using 2 Compared with conventional methods for D data, the new algorithm produces more accurate 1 D peak reconstruction and increased peak capacity. From the conventional 2D contour plot ( Fig.28A) counted 32 peaks and from only 1 D Chromatogram( Fig.9A ) counted 29 peaks, compared to the new 2D contour plot ( Fig.9F ) separated 40 peaks, corresponding to gains of 8 and 11 peaks for comprehensive 2D GC and single column 1D GC using conventional methods, respectively.

[0186] If desired, remove the waste / bypass line valve by permanently closing it and 1 The D and auxiliary flows share the same pressure / flow source, and the FRPM (and therefore the comprehensive 2DμGC) can be operated in stopped-flow mode. FIG. 30A to FIG. 30D shows the separation using this mode FIG. 9A to FIG. 9J The same 40 VOCs in 1 D. In case of strong flow disturbance, 1 Both separation time and peak width increase significantly. While this may be a disadvantage in certain operating paradigms, the operating flexibility of FRPM allowing stopped flow mode is useful for other applications.

[0187] In various aspects, the present disclosure provides a two-dimensional (2D) gas chromatography (GC) device incorporating a flow-restricted pneumatic modulator assembly that provides enhanced vapor separation capabilities compared to conventional 1D GCs and can be used for the analysis of highly complex chemical samples. In certain aspects, a microfabricated flow-restricted pneumatic modulator (FRPM) can be used in a portable comprehensive 2D GC that can achieve rapid 2 D injection and separation without affecting 1 D separation speed and elution peak distribution. The flow-through micro-photoionization detector (μPID) was used at the inlet and outlet of the FRPM to fully characterize the 2 D injection characteristics, such as injection peak width and peak height. 2 D / 1 When the D flow rate ratio is greater than 10, a speed of about 25 milliseconds can be achieved. 2 D injection peak width. Further comparison of FRPM with 0.5 m long 2 The Dμ column was integrated on the same chip and its performance was characterized. Finally, an automated portable comprehensive 2DμGC was presented, which included a 10mOV-1 1 Dμ column, with built-in 0.5m polyethylene glycol (PEG) 2 The integrated FRPM of the Dμ column and two μPIDs demonstrated the rapid separation of 40 volatile organic compounds in only about 5 minutes. 1 D and 2 The two μPIDs at the end of the Dμ column obtain1 D Chromatogram and 2 D chromatogram, and a 2D contour map was constructed.

[0188] In summary, the present disclosure provides a first-of-its-kind automated, portable, comprehensive 2D μGC using an integrated flow-restricted pneumatic modulator (FRPM). This compact, versatile device provides portable, independent separation of 40 VOCs in approximately 5 minutes with enhanced peak capacity compared to conventional 2D GC. 1 D and 2 Further integration of Dμ columns could further improve the compactness of the device, potentially allowing a handheld device to be suitable for more field applications.

[0189] For the purpose of illustration and description, the foregoing description of the embodiments has been provided. It is not intended to be exhaustive or to limit the present disclosure. The individual elements or features of a particular embodiment are generally not limited to that particular embodiment, but are interchangeable where applicable, and may also be used for a selected embodiment even if not specifically shown or described. It may also be varied in many ways. Such variants should not be considered to be out of the present disclosure, and all such modifications are intended to be included within the scope of the present disclosure.

Claims

1. A flow-limiting pneumatic modulator assembly for a multidimensional gas chromatography system, the flow-limiting pneumatic modulator assembly comprising: a first y-shaped fluid connector having a first inlet, a first channel having a first outlet, and a second channel having a second outlet, wherein the first inlet is configured to receive flow from a first chromatography column, the first outlet is configured to be in fluid communication with a second chromatography column, and the second outlet is configured to be in fluid communication with a downstream bypass line; a first flow resistor component disposed in the first channel, the first channel having a first flow resistance to the flow, wherein the second channel has a second flow resistance that is less than the first flow resistance; at least one flow control valve in fluid communication with the second outlet of the first y-shaped fluid connector; and a second y-shaped fluid connector, the second y-shaped fluid connector having a second inlet and a third inlet, the second inlet and the third inlet being connected to a third channel having a third outlet, wherein the second inlet is in fluid communication with the first outlet of the first y-shaped fluid connector and is configured to receive the flow from the first chromatographic column, the third inlet is configured to be in fluid communication with an auxiliary flow conduit upstream of the restrictive flow pneumatic modulator assembly, and the third outlet is configured to be in fluid communication with the second chromatographic column, wherein the restrictive flow pneumatic modulator assembly is configured to operate as an injector and modulator for the second chromatographic column.

2. The flow-limiting pneumatic modulator assembly according to claim 1, wherein: The second channel includes a second flow resistor component that exhibits the second flow resistance.

3. The flow-restricting pneumatic modulator assembly of claim 1, formed on a substrate.

4. The flow-limiting pneumatic modulator assembly of claim 1, wherein: The at least one flow control valve is a first flow control valve, and the flow-restricting pneumatic modulator assembly further includes a second flow control valve located upstream of and in fluid communication with the third inlet of the second y-shaped fluid connector.

5. The flow-limiting pneumatic modulator assembly of claim 4, wherein: The first flow control valve and the second flow control valve are respectively two-port valves each having an open position and a closed position.

6. The flow-limiting pneumatic modulator assembly of claim 4, wherein: in a first operating mode of the flow-restricting pneumatic modulator assembly, the first flow control valve and the second flow control valve are closed to direct the flow through the first channel, the first flow blocker component, the first outlet, to the third channel and the third outlet, and are configured to direct the flow to the second chromatography column; And in a second operating mode of the flow-limiting pneumatic modulator assembly, the first flow control valve and the second flow control valve are open to direct the flow through the second channel and the second outlet, and are configured to direct the flow to the bypass line, and the auxiliary fluid from the auxiliary flow conduit flows through the first flow blocker component and minimizes or blocks the flow of fluid through the first channel and the first outlet toward the second chromatographic column, and the first flow blocker component minimizes any interference caused by the flow of the auxiliary fluid in the flow in the first chromatographic column.

7. The flow-restricting pneumatic modulator assembly of claim 1, wherein: The at least one flow control valve comprises a three-way valve.

8. A multidimensional gas chromatography device, comprising: a first chromatographic column, the first chromatographic column receiving a fluid sample, the fluid sample comprising one or more target analytes; a flow restricting pneumatic modulator (FRPM) assembly disposed downstream of the first chromatographic column and in fluid communication with the first chromatographic column, wherein the FRPM assembly receives flow from the first chromatographic column and comprises: a first y-shaped fluid connector having a first inlet, a first channel having a first outlet, and a second channel having a second outlet; a first flow resistor component disposed in the first channel, the first channel having a first flow resistance to the flow, wherein the second channel has a second flow resistance to the flow, the second flow resistance being less than the first flow resistance; a second y-shaped fluid connector having a second inlet, a third inlet, and a third channel having a third outlet, wherein the second inlet is in fluid communication with the first outlet of the first y-shaped connector and receives the flow from the first chromatography column; and at least one flow control valve; an auxiliary fluid conduit disposed upstream of the FRPM assembly, wherein the third inlet of the second y-shaped fluid connector is in fluid communication with the auxiliary fluid conduit; a second chromatographic column disposed downstream of the FRPM assembly and in fluid communication with the third outlet of the second y-shaped fluid connector, wherein the FRPM assembly is configured to operate as an injector and modulator for the second chromatographic column; a bypass line disposed downstream of the FRPM assembly and in fluid communication with the second outlet of the first y-shaped fluid connector, wherein the at least one flow control valve controls flow to the bypass line; and At least one detector for detecting the presence of the one or more target analytes eluting from the stream after the stream passes through the second chromatography column.

9. The multidimensional gas chromatography apparatus according to claim 8, wherein: The at least one flow control valve is a second flow control valve, which is connected to the second outlet fluid of the first y-shaped fluid connector, and the multidimensional gas chromatography device also includes a first flow control valve, which is arranged upstream of the FRPM component and is connected to the third outlet fluid of the second y-shaped fluid connector.

10. The multidimensional gas chromatography apparatus according to claim 9, wherein: The first flow control valve and the second flow control valve are respectively two-port valves each having an open position and a closed position.

11. The multidimensional gas chromatography apparatus according to claim 9, wherein: In a first operating mode of the FRPM assembly, the first flow control valve and the second flow control valve are closed to direct the flow through the first channel, the first flow blocker member, the first outlet, the second inlet, and through the third channel to the third outlet to direct the flow to the second chromatography column; And in a second operating mode of the FRPM component, the first flow control valve and the second flow control valve are open to direct the flow through the second channel and the second outlet, and are configured to direct the flow to the bypass line, and the first flow blocker component minimizes or prevents fluid from flowing through the first channel and the first outlet toward the second chromatographic column.

12. The multidimensional gas chromatography apparatus according to claim 8, wherein: The at least one flow control valve comprises a three-way valve.

13. The multidimensional gas chromatography apparatus according to claim 8, wherein: The FRPM assembly further includes a second flow blocker component disposed in the second channel of the first y-shaped fluid connector, the second flow blocker component having a second flow resistance that is less than the first flow resistance.

14. The multidimensional gas chromatography device according to claim 8, further comprising a substrate, wherein: The FRPM component is formed in the substrate.

15. The multidimensional gas chromatography apparatus according to claim 8, wherein: The substrate further comprises: (i) the first chromatographic column located upstream of the FRPM assembly; (ii) a second chromatographic column located downstream of the FRPM assembly; or (iii) the first chromatographic column is located upstream of the FRPM assembly and the second chromatographic column is located downstream of the FRPM assembly.

16. The multidimensional gas chromatography apparatus according to claim 8, wherein: The at least one detector comprises a photoionization detector (PID). 17 . The multidimensional gas chromatography apparatus according to claim 8 , further comprising a second detector disposed downstream of the first chromatography column and upstream of the first inlet of the FRPM assembly.

18. The multidimensional gas chromatography apparatus according to claim 8, wherein: The first chromatographic column is a first micro gas chromatography column, and the second chromatographic column is a second micro gas chromatography column, wherein the multidimensional gas chromatography apparatus is portable.

19. A method for performing chromatographic analysis on a fluid sample comprising one or more target analytes in a multidimensional chromatography system, the method comprising: separating the one or more target analytes in the fluid sample in a first chromatographic column; Directing flow exiting the first chromatographic column toward a flow restricting pneumatic modulator (FRPM) assembly that operates as an injector and modulator for a downstream second chromatographic column, the flow restricting pneumatic modulator comprising: a first y-shaped fluid connector having a first inlet, a first channel having a first outlet, and a second channel having a second outlet; a first flow resistor component disposed in the first channel, the first channel having a first flow resistance to the flow, wherein the second channel has a second flow resistance to the flow, the second flow resistance being less than the first flow resistance; a second y-shaped fluid connector having a second inlet, a third inlet, and a third channel having a third outlet, wherein the second inlet is in fluid communication with the first outlet of the first y-shaped connector and receives the flow from the first chromatography column; and at least one flow control valve; operating the FRPM assembly for a first duration in a first operating mode in which the at least one flow control valve is closed to selectively direct the flow through the first channel, through the first flow blocker member, through the first outlet to the second inlet, through the third channel and the third outlet to a second chromatography column; and The FRPM assembly is operated for a second duration in a second operating mode in which the at least one flow control valve is open to direct the flow through the second passage and the second outlet and to a downstream bypass line.

20. The method according to claim 19, wherein: The at least one flow control valve includes: a first flow control valve, which is connected to the second outlet fluid of the first Y-shaped fluid connector upstream of the bypass line; and a second flow control valve, which is connected to the third inlet fluid of the second Y-shaped fluid connector, wherein the first flow control valve and the second flow control valve are respectively two-port valves each having an open position and a closed position.

21. The method according to claim 19, wherein: The first duration is less than or equal to approximately 0.2 seconds.

22. The method according to claim 19, wherein: In the first operating mode, the second chromatographic column has a peak injection width of less than or equal to about 25 milliseconds.

23. The method according to claim 19, wherein: A first flow rate of the stream in the first operating mode is less than or equal to approximately 0.5 ml / min, and a flow rate of the stream in the second operating mode is greater than or equal to approximately 1 ml / min.

24. The method according to claim 19, wherein: The multidimensional chromatography system also includes an auxiliary fluid conduit, which is located upstream of the FRPM component, wherein the at least one flow control valve includes a first flow control valve and a second flow control valve, the second flow control valve is configured to receive auxiliary fluid from the auxiliary fluid conduit upstream of the third inlet of the second y-shaped fluid connector, and the auxiliary fluid conduit is connected to the second chromatographic column fluid, so that in the second operating mode, the auxiliary fluid flows through the first flow blocker component and minimizes or prevents the fluid from flowing through the first channel and the first outlet toward the second chromatographic column, and the first flow blocker component minimizes any interference caused by the flow of auxiliary fluid in the flow in the first chromatographic column.

25. The method according to claim 24, wherein: The flow entering the second chromatographic column during the first operating mode has a first flow rate, and the auxiliary fluid entering the second chromatographic column during the second operating mode has a second flow rate, wherein a ratio of the second flow rate to the first flow rate is greater than or equal to about 10:

1.

26. The method of claim 19, wherein: The method further includes repeatedly operating the FRPM component in the first operating mode for the first duration and operating the FRPM component in the second operating mode for the second duration.

27. The method according to claim 26, wherein: The FRPM component has a duty cycle of greater than or equal to about 1% to less than or equal to about 50%.

28. The method of claim 19, further comprising detecting one or more target analytes in the auxiliary flow exiting the second chromatography column.

29. The method of claim 28, further comprising detecting one or more target analytes in the flow exiting the first chromatography column.

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