GB2059796A - Controlling a sample fluid flow or volume a carrier fluid - Google Patents

Abstract

Acoustic standing waves are used to impede the flow of a sample fluid relative to a carrier fluid, eg in chromatographic analysis. A controlled source 12 of a carrier fluid feeds a carrier fluid to one end of a tube 2. A source 20 of sample fluid is connected to an inlet port 14 at a location between two adjacent nodes 36 in a standing wave generated by an acoustic signal generator 4. The sample fluid flows across tube 2 to an exit port 24 and satwates the fixed volume between the nodes to provide a sample of predetermined volume. Cessation or reduction of the standing waves then allows the carrier gas flow to sweep the sample out of the other end of tube 2. That end of the tube is connected to a chromatographic column 30 with an associated detector 32. The column 30 has a sonic generator 42 which produce a standing wave pattern in the column 30, the nodes of this pattern acting as separation plates in the column. <IMAGE>

Description

SPECIFICATION Controlling a sample fluid volume in a carrier fluid The present invention relates to means for controlling a quantity of a sample fluid in a chamber filled with a carrier fluid, and more specifically to chromatographic analyzers.

The use of chromatographic analyzers for analyzing fluid samples, e.g., gas mixtures, is well-known. A sample injection means is used for injecting a sample of the gas to be analyzed into a carrier fluid stream to be carried to the chromatographic separating column.

The purpose of the sample injector is two-fold; it must inject a sample into the carrier fluid stream and it must provide a means for predetermining the volume of the sample to be injected. The prior art sample injection devices have included mechanically operated syringes, valves having internal storage loops, and other complicated mechanical devices which have usually been unable to provide long term reliability in combination with a low manufacturing cost. Accordingly, it would be desirable to provide a sample injection apparatus capable of having extremely long operating life as well as a simple and inexpensive structure.

The column of a chromatographic analyzer produces separation of fluid mixtures as a result of their variable passage time through the column in response to the application of carrier gas, as is well-known. However, such columns have fixed parameters and operate very slowly as a result of the need to pass the fluid mixture through a column tightly packed with fluid separating particles having a large surface area. Attempts to produce a so-called open column to improve mobility time resulted in several prior art devices, such as a column having only a coated interior wall and a so-called ion mobility spectrograph or plasma chromatograph. In the latter device an electric field is applied to an open column to produce a separation of a previously ionized gas mixture which is swept through the column by a carrier gas.It would be desirable to provide a separator capable of separating components of a fluid mixture without the disadvantages of the prior art fluid separators.

Accordingly the present invention provides apparatus comprising a chamber containing a first (carrier) fluid, and acoustic signal generating means which generate, in the chamber, standing acoustic waves which form barriers to the movement of a second (sample) fluid relative to the first.

According to one aspect, the invention is used in apparatus arranged to allow the injection of a predetermined volume of the sample fluid into the chamber, comprising fluid sample injection means which introduce a fluid sample into the space between an adjacent pair of nodes of the standing waves.

According to another aspect, the invention is used in a chromatographic analyzer wherein the chamber is a chromatographic column, including means which inject a quantity of sample fluid into the chamber, and means which supply a flow of carrier fluid to one end of the chamber and thereby sweep the sample fluid along the chamber through the barriers formed by the standing waves to an exit at the other end.

The analyzer may further include apparatus in accordance with the invention arranged to allow the injection of a predetermined volume of the sample fluid into a chamber, from which it is then passed into the chromatographic column.

A chromatographic analyzer in which the invention is applied twice in this manner will now be described, by way of example, with reference to the drawing, in which: Figure 1 is a diagrammatic illustration of the analyzer, and Figure 1A shows a modification of part of the analyzer.

Referring to Fig. 1, the sample injection apparatus has a hollow chamber in the form of a cylindrical tube 2, and an acoustic signal generator 4 drives an electro-acoustic transducer 6 mounted at one end of the tube 2 as shown. The transducer 6 may be any suitable device such as a piezoelectric element capable of producing acoustic signals when suitably driven by an electrical signal. Adjacent to the end of the tube with the acoustic signal output device 6, there is a first fluid inlet port 8. The term fluid as used herein refers to gases and liquids, since the present injection apparatus is useable with either fluid medium.

A source of the carrier fluid 12 is connected to the inlet port 8 via an electrically controlled fluid valve 10.

At a suitable distance along the tube 2, as determined by the presence of the nodes of a standing wave within the tube 2, as discussed more fully hereinafter, there is a second inlet port 14. A sample source 20 of a sample to be analyzed is connected to the port 14 via a fluid sample conduit 18 and a second fluid valve 16, and a fluid exhaust port 22 is connected to the conduit 18 between the valve 16 and the source 20. A fluid outlet port 24 is located in the wall of the tube 2 opposite the second inlet port 14, and is connected to a third fluid exhaust conduit 28 via a third fluid valve 26.

The other end of the tube 2 is connected to the input of a chromatographic separating column 30, and a chromatographic detector 32 is connected to the output of the column 30. A timing and control means 34 is used to control the frequency and output energy level of the acoustic generator 4 and signal producing means 6 and the fluid valves 10, 16 and 26.

In operation, the present sample injection apparatus is used to measure a sample volume and to inject, or transport, that volume of the sample to be analyzed to the chromatographic column 30. In order to determine the volume of the sample to be provided, the frequency of the acoustic generator is adjusted by the timing and control circuit 34 to produce standing waves having nodes 36 separated by the desired spacing to produce the sample volume. For example, a 150 kHz frequency would produce acoustic nodes 1 mm apart in air. The tube 2 may have an internal diameter of 10 mm and a length of 100 mm. The location of the sample injection port 14 and sample exit port 24 is predetermined to lie at or near an antinode between two adjacent nodes in the standing waves produced by the acoustic signal from the acoustic generator 4.

During this initial phase of the operation of the injection apparatus, the valves 10, 16 and 24 are closed by the timing and control circuit 34. After the acoustic signal has been established within the column 2, the sample injection port control valve 16 and the sample exit port control valve 26 are opened by the circuit 34. This allows the sample from the sample source 20 to flow through the fluid conduit 18 past the valve 16 into the inlet port 14. The sample continues across the space between the nodes of the standing waves in the hollow tube 2 into the exit port 24 and exits via the via exit valve 26 and the fluid exhaust conduit 28. After a predetermined period of time, the volume between the two nodes on either side of the inlet port 14 and the outlet port 24 will be saturated by the sample.At this time, the valves 16 and 26 are closed by circuit 34 to trap the sample of the sample fluid to be analyzed between the nodes within the column 2. Subsequently, the carrier gas control valve 10 is opened by circuit 34. This allows the carrier fluid from the carrier fluid source 12 to enter the column 2 and to sweep the sample of the fluid to be analyzed, which is present within the column 2, into the chromatographic column 30 for separation and into the chromatographic detector 32.

The circuit 34 may reduce the acoustic energy from the acoustic generator 4 and transducer 6 to prevent any possible interference with the transportation of the sample by the carrier fluid 12 into the chromatographic column 30. Thus the sonic energy would be elevated during the trapping phase of the sample between the standing wave nodes and subsequently reduced when the carrier gas is introduced into the column 2. The sonic energy during the sample trapping phase should be high enough to prevent the sample fluid from migrating past the standing wave nodes within the column 2. Further, it should be noted that the size of the sample may be discretely varied by varying the acoustic frequency by an adjustment of the acoustic generator 4 by the circuit 34. Additionally, a pressure sensor 38 may be mounted on the column 2 sense the internal pressure representative of the nodes 36.An output signal from the sensor 38 would be applied to the control circuit 34 to effect a requisite frequency control of the acoustic generator 4 to ensure a proper location of the nodes 36 within respect to the ports 14 and 24.

The chromatographic column 30 is a tube of uniform internal diameter having an acoustic, or sonic, transducer 40 at one end thereof arranged to introduce sonic waves into the column under the control of a sonic generator 42 and controller 44 which may be any suitable means for controlling frequency of operation of the sonic transducer 40 in response to input control signals applied thereto. The controller 44 is also effective to provide an output signal representative of the start of energization of the transducer 40 for use as hereinafter described. The fluid sample from tube 2 is carried by carrier fluid from injection port 8 into the tube 30 as shown.

The other end of the tube or column 30 has a closed sonic reflecting end 46 and an outlet port 48 connected to the chromatographic detector 32, which detects the separated components of the fluid sample and provides representative output signals, e.g. to a recorder.

A plurality of irregularly spaced pressure detectors 50 are located in the wall of the column 2 near the exit port 48 to provide signals indicative of the presence of nodes and anti-nodes in the standing acoustic waves created within the column 30 by the sonic transducer 40. These sonic wave position representative signals are fed to the sonic controller 44.

Instead of using a horizontal chromatographic column 30 as shown, the column may be placed vertically with the sample being introduced at the top.

A further modification is shown in Fig. 1A where a light source 56 is arranged to project a beam of light through the column 30 to a detector 60. The column may have wholly transparent walls or transparent windows. The detector 60 feeds a recorder 62 to provide a record of the passage of the separated constituents of the fluid sample past the detector 60.

In operation, the chromatographic column 30 is energized by the sonic controller 44 which activates the sonic generator 42 and transducer 40 to produce sonic waves within the hollow column 30, which is of a suitable length such as 50 cm. The acoustic transducer fills the column 30 with a succession of alternate nodes and anti-nodes of standing sonic waves. Subsequently, the sample and carrier source 2 is operated to apply the sample and carrier fluid into the interior of the column 30. The continued application of the carrier fluid ultimately forces the fluid sample through the column 30 to the column outlet port 48.

The sonic nodes in the column 30 function as the plates of a conventional chromatographic column, with the plate number being represented by the frequency of the acoustic signal and the plate height being equivalent to the wavelength of the standing waves. The different packing materials and/or partition coatings used in conventional chromatographic columns are functionally represented by the sonic energy levels within the column 30.

The separation of the sample into its constituents is believed to be a graduated effect dependent on the size of the molecules. Specifically, larger molecules are retained at the sonic nodes, i.e., high pressure areas, for longer periods of time than smaller molecules by virtue of the larger surface area of the molecules which are affected to a greater extent by sonic energy. Consequently, different size molecules are retarded corresponding amounts in travelling through the column 30 and so are separated according to the size of the molecules in the fluid sample mixture.

While a variation in column length may obviously be obtained by physically extending the physical length of the column 30, a more convenient way of controlling the effective column length without a physical alteration thereof can be obtained by the use of moving acoustic waves. Depending on the direction of wave motion, i.e., upstream or downstream with respect to the entry and exit ports, moving the pressure nodes can increase the separation by an upstream movement of the nodes or decrease the separation by a downstream movement of the nodes during the separation process. Thus, a variation in apparent column length can be simply and easily achieved without an actual physical change in the measured length of the column 30 and may be quickly accomplished at any time during the separation process.Since the resonant, or standing wave, operation is the most efficient in terms of loss of sonci energy, a moving wave made of operation would require a change in acoustic frequency and amplitude to a non-resonant mode.

The plate height would vary according to the frequency employed and the nature of the sample mixture since this would alter the speed of the acoustic signal in the column 2.

For example, if the acoustic frequency is 1 50kHz, then the plate height will be approximately 1 mm in air. However, as soon as the mixture of carrier and sample fluids are introduced into the column 30, the plate height will change. The irregularly spaced sonic pressure detectors 50 are used to detect the shift in the sonic nodes and anti-nodes, i.e., sonic wave position, and to provide signals to the sonic controller 44 for altering the frequency to restore the plate height. The separated fluid sample is ultimately swept out of the column 30 through the exit port 48 by the carrier fluid into a conventional chromatographic detector 32. The output of the detector 32 may be applied to a recorder or other associated circuitry.

It should be noted that since the pressure detectors 50 provide concurrent output signals indicative of the effect of the carrier and sample fluids on the sonic node and anti-node position in the column 30, these output signals could also be used as an indication of the type of material being introduced by the fluid sample since the carrier fluid would have a constant consistuency. Such an interpretation of the output signals from the pressure detectors 50 could be used instead of the chromatographic detector 32 and applied directly either to a recorder or to a digital computer for more detailed analysis.The analysis of the output signals from the pressure detector 50 would involve a comparison of the acoustic wave pattern before the introduction of the sample fluid into the volume of the column monitored by the pressure detectors with the acoustic wave pattern during the presence of the sample fluid. This comparison operation could employ successive signals from the detectors 50, a second group of irregularly spaced detectors spaced from the detectors 50, e.g. near the entrance to the column, or a stored group of pressure data signals in a computer memory. In general, such a comparison would provide an analysis, i.e. identification, of the separated sample constitutents by measuring the acoustic wave pattern deviation, i.e. shift, based on known deviations of reference fluids.

If the chromatographic column 30 is located in a vertical position, the assistance of gravity is obtained in addition to the sample transporting action provided by the carrier fluid during the fluid separation process. This orientation of the separation column might be particularly useful in separating body fluid components which are introduced into the column, e.g., blood cells, bacteria, etc. In this arrangement the carrier fluid, e.g., air, and gravity are jointly effective to transport the body fluids through the separation column. If the optical detection system of Fig. 1A is also used, the passage of the separated constituents is detected by detecting the optical density differences between the fluid sample constituents and the carrier fluid. The separated constituents are ultimately swept out of the exit port 48 by the carrier fluid. In either case, the resolution of the separation can be controlled by selecting a frequency, i.e., plate height, and the partition coefficient can be controlled by changing the amplitude of the sonic waves to "tune" the separation process by easily changing the column parameters.

Further, the extremely small pressure drop across the column simplifies the introduction of a fluid sample.

Obviously there must be sufficient acoustic isolation between the chamber 2 and the tube 30 to avoid interference effects.

Claims (15)

1. Apparatus comprising a chamber containing a first (carrier) fluid, and acoustic signal generating means which generates, in the chamber, standing acoustic waves which form barriers to the movement of a second (sample) fluid relative to the first.

2. Apparatus according to Claim 1, arranged to allow the injection of a predetermined volume of the sample fluid into the chamber, comprising fluid sample injection means which introduce a fluid sample into the space between an adjacent pair of nodes of the standing wave.

3. Apparatus according to Claim 2, wherein the injection means inject the sample through a port on one side of the chamber, and there is an exhaust port on the opposite side of the chamber through which displaced fluid is exhausted.

4. Apparatus according to either of Claims 2 and 3, wherein the chamber is tubular with the acoustic signal generating means at one end.

5. Apparatus according to any of Claims 2 to 4, including a carrier fluid injection means located to one side of the injection space and an exit port located to the other side of the injection space.

6. Apparatus according to Claim 5, including control circuitry which operates valves controlling the fluid sample injection means and the carrier fluid injection means alternately.

7. Apparatus according to Claim 6, wherein the control circuitry reduces the energization of the acoustic signal generating means while the carrier fluid injection means is operating.

8. Apparatus for injecting a predetermined volume of fluid into a chamber substantially as herein described and illustrated.

9. Apparatus according to claim 1, wherein the chamber is a chromatographic column, including means which inject a quantity of sample fluid into the chamber, and means which supply a flow of carrier fluid to one end of the chamber and thereby sweep the sample fluid along the chamber through the barriers formed by the standing waves to an exit at the other end.

10. Apparatus according to Claim 9, including pressure sensor means located in the wall of the chamber, the acoustic signal generating means being controlled in response thereto.

11. Apparatus according to either of Claims 9 and 10, wherein the chamber is arranged vertically with the fluid carrier flow being downward.

12. Apparatus according to any of Claims 9 to 11, including an optical sensor near the exit which senses the passage of separated components of the sample fluid as they pass the detector.

13. Apparatus according to any of Claims 9 to 12, including means for detecting the acoustic wave patterns in the chamber with and without the presence of the sample fluid and determining therefrom the separated components of the sample fluid.

14. A chromatographic column substantially as herein described and illustrated.

15. A chromatographic analyzer comprising apparatus for injecting a predetermined volume of fluid into a chamber according to any of Claims 2 to 8 and a chromatographic column according to any of Claims 9 to 14.