This disclosure relates to measuring fluid density.
In supercritical fluid chromatography (SFC), the separation is often controlled by a back pressure regulator (BPR). The BPR is used to control the pressure at an outlet of a separation column or a high pressure detector. This pressure affects the density of the mobile phase, which, in turn affects the separation.
The disclosure is based, in part, on the realization that a more direct means of controlling and monitoring density of a mobile phase in a supercritical fluid chromatography (SFC) system can be possible by using a low volume, flow-through device to measure the density of the mobile phase passing through it and hence provide an output signal that can be used for control and monitoring.
One aspect provides an apparatus that includes a vibration element defining a fluidic passageway; an excitation element for exciting vibration of the vibration element; a detector for providing a signal representative of the frequency excited; and control electronics configured to determine a density of a fluid flowing through the fluidic passageway based, at least in part, on the signal provided by the detector. The vibration element is configured such that Coriolis force induced twisting of the vibration element is substantially inhibited.
Another aspect features A method that includes measuring a density of a mobile phase fluid in a chromatography system by passing the mobile phase fluid through a flow-through member of a DMD, and controlling operation of one or more other devices of the chromatography system based on the measured density.
In yet another aspect, a chromatography system includes a separation column; a pump for delivering a mobile phase fluid flow to the separation column; a vibration element defining a passageway in fluidic communication with the pump; an excitation element for exciting vibration of the vibration element; a detector for providing a signal representative of the frequency excited; and control electronics configured to determine a density of the mobile phase fluid flow based, at least in part, on the signal provided by the detector.
Implementations may include one or more of the following features.
In some implementations, the vibration element includes a u-shaped flow-through member that defines the fluidic pathway.
In certain implementations, the flow-through member includes a fused silica tube.
In some implementations, the flow-through member includes a diffusion bonded titanium substrate.
In certain implementations, the flow-through member includes an inlet segment and an outlet segment which are connected by a connecting segment, and the vibration element includes one or more cross-members which extend between the inlet and outlet segments to inhibit Coriolis force induced twisting of the vibration element.
Some implementations also include a housing defining a chamber. The vibration element is cantilever mounted within the chamber, and the chamber is evacuated to provide a vacuum.
In certain implementations, the detector is mounted external to the housing, and the housing includes at least one transparent wall to allow optical communication between the detector and the vibration element.
In some implementations, measuring the density of the mobile phase fluid in the chromatography system comprises: driving a vibration element that includes the flow-through member to vibrate; and monitoring the vibration motion of the vibration element with a detector of the DMD.
In certain implementations, driving the vibration element includes applying a sine-wave signal to an excitation element to excite vibration of the vibration element.
In some implementations, the vibration element includes one or more cross-members which inhibit Coriolis force induced twisting of the vibration element as it vibrates.
In certain implementations, controlling operation of the one or more other devices of the chromatography system includes adjusting a pressure setting of a back pressure regulator of the chromatography system, and thereby adjusting the density of the mobile phase fluid.
In some implementations, controlling operation of the one or more other devices of the chromatography system includes adjusting a flow rate from a solvent delivery pump.
In certain implementations, controlling operation of the one or more other devices of the chromatography system includes controlling operation of a proportioning valve to achieve desired proportions of solvents in the mobile phase fluid.
In some implementations, the control electronics are configured to adjust operation of the at least one pump based on the density of the mobile phase fluid flow.
Certain implementations also include a back pressure regulator for regulation an operating pressure of the system. The control electronics can be configured to adjust a pressure setting of the back pressure regulator based on the density of the mobile phase fluid flow.
Some implementations also include a proportioning valve for regulation an operating pressure of the system. The control electronics can be configured to adjust a pressure setting of the back pressure regulator based on the density of the mobile phase fluid flow.
In certain implementations, the chromatography system is supercritical fluid chromatography system.
In some implementations, the chromatography system is a liquid chromatography system
Other aspects, features, and advantages are in the description, drawings, and claims.
Like reference numbers indicate like elements.
The vibration element 112 includes a u-shaped flow-through member 124 that defines the fluidic passageway 118. The fluidic passageway 118 can have a cross-sectional area of about 100 square microns to about 50,000 square microns and a volume of 50,000 to 150,000,000 cubic microns. The flow-through member 124 has a wall thickness (t) of 10 microns to 20 microns. Generally, the smaller the wall thickness is, the more sensitive the device will be because the fluid within the tube will make up a greater proportion of the total mass of the vibration element 112.
The flow-through member 124 may be formed from a fused silica tube or fused silica capillary tubing comprising a fused silica capillary tube covered with a polyimide coating, metal tubing, a micromachined silicon structure, or diffusion-bonded titanium sheets, or a combination of such materials. In one example, the flow-through member 124 can be formed from a fused silica capillary tube having a 50 micron to 100 micron inner diameter fluidic passageway 118 and a 10 micron to 20 micron wall thickness. Fused silica can be preferable given its relatively high quality (Q) factor.
The flow-through member 124 includes an inlet segment 130 and an outlet segment 132 which are connected by a u-shaped connecting segment 134. Distal ends regions 136a, 136b of the inlet and outlet segments 130, 132 extend into and are mechanically secured (e.g., via clamping, laser welding, epoxy, etc.) to a base portion 136 of the housing 116 such that the flow-through member 124 is cantilever mounted within the chamber 114 and inlet and outlet portions of tubing forming the flow-through member 124 extend outwardly from the housing 116 to permit external fluidic connection to the vibration element 112.
Cross-members 138a, 138b extend between the inlet and outlet segments 130, 132 and are secured thereto (e.g., via laser welding, epoxy, etc.). The cross-members 138a, 138b help to inhibit (e.g., prevent) Coriolis force induced twisting of the vibration element 112 about longitudinal axis 140 (
The housing 116 surrounding the vibration element 112 is formed of a rigid material such as metal and/or plastic, and the chamber 114 is evacuated to provide a vacuum which helps to reduce (e.g., eliminate) any influence of fluid surrounding the vibration element 112 that might otherwise change the resonant frequency of the vibration element 112. To induce vibration, excitation element 120 is provided in the chamber 114 and is positioned above one of the cross-members 138a. The excitation element 120, driven by control electronics 160, applies a time varying cyclical force. The force can be electrostatic, magnetic, and/or mechanical. In one example, the excitation element 120 is a conductive plate to provide an electrostatic force between the conductive plate and the cross-member to induce movement of the vibration element 112.
The detector 122 provides a signal (detected signal) representative of the excited frequency to the control electronics 160. In the illustrated example, the detector 122 includes a light source 148 and a photocell 150 is utilized for providing a signal representative of the excited frequency of vibration. The light source 148 (e.g., a light-emitting diode, laser diode, etc.) sends light in to reflect off one of the cross-members 138b, which may be provided with a polished, reflective surface, and the photocell 150 is arranged to measure the scattered light that reflects off of the vibration element 112 as an indication of phase angle. The measurements from the photocell 150 are delivered to the control electronics 160. Electrical connections to the detector 122 and/or the excitation element 120 can be made by passing conductive wires through walls of the housing 116, and openings for the conductive wires are sealed to support a vacuum in the chamber 114. While some conventional flow meters rely on Coriolis induced twisting for the purpose of measuring mass flow, this is undesirable for measuring density as the scattered light signal measured by photocell 150 will contain amplitude variations with frequency components relating to the Coriolis induced vibrations. This interferes with the ability of the control system to drive the sensor at resonance.
The control electronics 160 can include non-volatile memory with computer-readable instructions; and at least one processor for executing computer-readable instructions, receiving input, and sending output. The control electronics 160 can also include one or more digital-to-analog (D/A) converters for converting digital output from the at least one processor to an analog signal. The control electronics 160 can also include one or more analog-to-digital (A/D) converters for converting an analog signal, such as from the photocell 150, to a digital signal for input to the at least one processor. The control electronics 160 can also include a function generator, controlled via the at least one processor, to provide a sine wave signal to the excitation element 120. In some implementations, the control electronics 160 can include memory with computer-readable instructions for controlling operation of one or more devices such as fluid pumps, valves, etc. In some cases, various features of these control electronics can be integrated in a microcontroller.
The control electronics 160 use the measurements to modulate the sine-wave excitation signal in order to match the sine-wave frequency to the resonant frequency of the vibration element 112. In this regard, the control electronics 160 can modulate the excitation signal to maintain a constant phase angle of 90 degrees between the excitation signal and the detected signal. The excitation signal then becomes a measure of the resonant frequency which is affected by the mass of the vibration element 112, which, in turn, is affected by a density of a fluid within the vibration element 112. Once the resonant frequency is known, the control electronics 160 can calculate the fluid density from the following equation, for example:
Where, ρfluid is the density of the fluid in the passageway 118, which is to be calculated; melement is the mass of the vibration element 112, which is a known value; Vpassageway is the internal volume of the passageway 118, a known value; ffull is the resonant frequency of the vibration element 112 filled with a fluid as measured with the apparatus 100, which is determined experimentally as described above; and fempty is the resonant frequency of the vibration element 112 when the passageway 118 is empty, which may be determined experimentally by operating the apparatus 100 without any fluid flow.
The apparatus may, for example, advantageously be utilized in a supercritical liquid chromatography (SFC) system to monitor density of the mobile phase (CO2). For example,
The CO2 and co-solvent fluid flows from the first and second pumps 210, 212, respectively, and are mixed at a tee 214 forming a mobile phase fluid flow. The mobile phase fluid flow passes through the vibration element 112 (
From the injector valve 216, the mobile phase flow containing the injected sample plug continues through a separation column 218, where the sample plug is separated into its individual component parts. After passing through the separation column 218, the mobile phase fluid flow continues on to a detection device 220 (e.g., a flow cell/photodiode array type detection device) then on to a back pressure regulator (BPR) 222 before being exhausted to waste 223.
Also shown schematically in
Alternately or additionally, it may be advantageous for DMD 110 to be positioned between pump 210 and mixing tee 214, or between column 218 and BPR 222.
Also since the density of liquids is a function of temperature, it may be advantageous for both the temperature of the flowing fluid and of DMD 110 to be controlled.
Although a few implementations have been described in detail above, other modifications are possible. For example, in some implementations, the flow-through member may be formed from a diffusion bonded titanium (Ti) substrate.
After the three substrate layers are bonded together, the groove 329 formed in the inner substrate layer 327a is enclosed by the first and second outer substrate layers 327b, 327c, thereby providing an enclosed passageway 318 through which fluid can flow. The first and second outer substrate layers 327b, 327c form the outer surface of the diffusion bonded substrate 325, and the through-holes 331 formed in the first and/or the second outer substrate layers 327b, 327c form inlet and outlet openings 326, 328 allowing for fluid communication with the fluid passageway 318. In some cases, fittings 333 can be mounted to the outer surface of the diffusion bonded substrate 300 to assist in establishing fluidic connections between fluidic tubing and the through holes 331.
Portions of the substrate are etched away to define an inlet segment 330 and an outlet segment 332 which are connected by a connecting segment 334, and integral cross-members 338a, 338b that extend between the inlet and outlet segments 330, 332. As in the implementation described above with respect to
The substrate 325 is partially enclosed within an evacuated chamber 314 of a housing 316, with a distal end portion including the through-holes 331 extending outwardly from a base portion 339 of the housing 316 to permit fluidic connection to the vibration element 312. The substrate is mechanically secured (e.g., via laser welding or epoxy) to the base portion 339 of the housing 316 such that the flow-through member 324 of the vibration element 312 is cantilever mounted within the chamber 314.
As in the implementations described above, the flow-through member 424 includes an inlet segment 430 and an outlet segment 432 which are connected by a u-shaped connecting segment 434, and cross-members 438a, 438b are provided to help to inhibit (e.g., prevent) Coriolis force induced twisting of the vibration element 412. Distal ends regions 436a, 436b of the inlet and outlet segments 430, 432 extend into and are mechanically secured to a base portion 439 of a housing 416 such that the flow-through member 424 is cantilever mounted within an evacuated chamber 414 of the housing 416 and polyimide covered end portions of the tubing extend outwardly from the housing 416 to permit fluidic connection to the vibration element 412. Fittings, such as compression screw and ferrule fittings commonly used in chromatography applications, can be provided for connecting the fluidic tubing, e.g., to a separation column.
While an optical detector for providing a signal representative of the excited frequency have been described, other options for detection means may be in the form of, for example, magnetic means, or a strain gauge mounted to the surface of the vibration element.
Furthermore, while a detector has been described as being inside of the housing, the detector may instead be disposed outside of the housing. For example,
It may be advantageous, for example, in systems with splitters, to have more than one DMD-based control loop.
It may also be advantageous to incorporate apparatus for measuring fluid densities in conventional High Performance Liquid Chromatography (HPLC) and/or Ultra High Performance Liquid Chromatography (UHPLC) systems. For example,
In the illustrated example, a DMD 110 is positioned between the proportioning valve 712 and the pump 710 to measure the density of mixed mobile phase fluid. The control electronics 160 can then use the measured density to determine whether the mixed mobile phase includes the desired proportions of the solvents. And, if it is determined that the mixed mobile phase does not include the desired proportions of the first and second solvents, the control electronics 160 can then control operation of the proportioning valve 712 to achieve the desired solvent proportions.
Accordingly, other implementations are within the scope of the following claims.
This application claims priority to and benefit of U.S. Provisional Patent Application No. 61/661,454 entitled “Measuring Fluid Density,” filed Jun. 19, 2012, which is incorporated by reference herein in its entirety.
Number | Date | Country | |
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61661454 | Jun 2012 | US |