Tovatech announces FlowCal 5000 Flow Meter for HPLC systems
4 stars based on
Year of fee payment: A method and apparatus for monitoring and controlling nano-scale flow rate of fluid in the operating flow path of a HPLC system provide fluid flow without relying on complex calibration routines to compensate for solvent compositions gradients typically used in HPLC.
The apparatus and method are used to correct the flow output of a typical, analytical-scale 0. The present invention relates to a flow sensing method and apparatus and more particularly to a flow sensing method and apparatus used to monitor and provide feedback to a closed-loop flow control of an analytical-scale high performance liquid chromatography HPLC system which enables the delivery of stable flow to a nano-scale chromatographic system using a micro-scale or normal scale chromatographic pump.
Unfortunately, typical analytical-scale HPLC liquid flow meter for hplc pump technology does not scale well to these low flow rates as the constant-flow open-loop analytical-scale pumps typically used for analytical-scale chromatography 0.
Traditional plunger displacement pumping systems have been successful in delivering stable, accurate flows in the normal-scale and micro-scale high performance liquid chromatography regimes. While normal-scale HPLC is performed with mobile phase flow rates of about 0. Current plunger displacement pumping systems typically cannot deliver nano-scale HPLC flow rates with reliability and accuracy. One method for providing nano-scale flow rates in an HPLC system is to use a flow-divider which directs a majority of flow from the pump to a waste stream and a small portion of the pump output to the HPLC working stream i.
Unfortunately, liquid flow meter for hplc pump order to operate a HPLC system in split-flow mode the user must calculate the split ratio of the system. To calculate the split ratio, the user must know the permeabilities liquid flow meter for hplc pump both the split restrictor and the chromatographic system i. These permeabilities are used to calculate the flow rate that must be supplied by the normal-scale or micro-scale HPLC pump to produce the desired flow through the chromatographic system.
Although it is possible to calculate split restrictor dimensions that should provide a desired split ratio, changes in permeability of either the split restrictor or chromatographic column over time cause unpredictable split ratio variations. Such variations result in unacceptable flow variations through the chromatographic column.
One possible solution to the problem of changing split ratios is to monitor the flow to the chromatographic column with an appropriate flow sensor. Fluid flow rates can be determined by measuring the pressure of a liquid flowing through a restrictor.
Assuming a constant viscosity, the back pressure of liquid flowing through a restrictor will scale linearly with the flow rate of the liquid. The flow rate is measured by placing a pressure transducer before and after a restrictor inline with the flow. Signals from the pressure transducers are electronically subtracted and amplified to achieve a high degree of common-mode noise rejection. This permeability is sufficient for providing a flow measurement while not inducing much fluidic load on the pump.
However, pressure measuring flow sensors must be calibrated to compensate for the different viscosity of each fluid being measured. This creates a great disadvantage in liquid chromatography applications wherein fluid composition varies dramatically over the course of a chromatography run.
Liquid flow meter for hplc pump method that can be used to sense fluid flow is thermal flow sensing. The tube of the flow sensing device is made from materials of low thermal conductivity i. A temperature profile will develop when a discrete section of the fluid in the tube is continuously heated, under a zero flow condition. The shape of this temperature profile will depend upon the amount of heat added to the fluid and the upstream and downstream temperatures of the liquid.
Assuming identical upstream and downstream fluid temperatures, under a zero-flow condition, liquid temperatures measured at first and second sensor will be equal as thermal diffusion will be equal in both directions.
If the liquid in the tube is permitted to flow, the fluid temperatures at the first and second sensor will depend upon the rate of liquid flux and the resulting heat convection.
As liquid begins to flow past the heated zone, a temperature profile develops. In addition to the symmetric diffusion of the heat, liquid flow meter for hplc pump convection of the heated fluid will occur in the direction of the fluid flow. Therefore, under flowing conditions, fluid temperatures measured at the first and second sensor will be different. Temperature measurements made at the first and second sensor are sampled, subtracted and amplified electronically in situ to provide a high degree of common-mode noise rejection.
This allows discrimination of extremely small upstream and downstream temperature differences. By appropriate placement of temperature measurement probes i. However, like pressure measuring flow sensors which must be calibrated to compensate for the different viscosity of each fluid being measured. Thermal based flow sensors also need such calibration. This at times creates a disadvantage in liquid chromatography applications wherein fluid composition varies dramatically over the course of a chromatography run.
Other pump solutions for creating the low flow rates required by nano-scale LC involve single-stroke syringe pumps. These pumps have a fixed delivery volume. As a result run times may be limited by the length of the pump stroke.
Time is required between each run to refill the pump. During this refill cycle, the chromatographic system must depressurize, then re-pressurize to start the next run. Additionally, Nano-scale LC systems are often coupled to mass spectrometers. Electro-spray interfaces typically used in LC-coupled mass spectrometers are most stable when constantly flowing. The stop-flow conditions existing during refill cycles of syringe-type pumps as noted above may destabilize the electro-spray mass spectrometry interface.
Some embodiments of the present invention involve liquid flow meter for hplc pump method and apparatus for monitoring and controlling the nano-scale flow rate of fluid in an operating flow path of a HPLC system without relying on complex calibration routines to compensate for solvent composition gradients typically used in HPLC.
According to some of these embodiments of the invention, an apparatus and method is used to correct the flow output of a typical, analytical-scale 0. According to one embodiment of the invention, the analytical-scale constant flow-source HPLC pumps used are modified commercially available pumps.
Typically, analytical-scale HPLC pumps use stepper-motor driven linear actuators. Depending on the pump architecture, the change required to enable low-flow delivery involves modifying the gearing of the pump drive mechanism offering a higher incremental drive resolution.
In a first illustrative embodiment, delta-P type flow meters, as in-line sensors, are used within the inventive apparatus. Fluid flow from a first pump in an operating path flows through an initial in-line pressure liquid flow meter for hplc pump and through a restriction element and is mixed with liquid flow meter for hplc pump flow from a second pump within a second operating path having a second in-line sensor and restriction element at a fluidic cross.
Pressure at this fluidic cross liquid flow meter for hplc pump measured by a fluidic cross pressure transducer. According to the invention, a pressure drop measured between the first and second inline flow sensors and the pressure at the fluidic cross will be proportional to the flow delivered by the first and second pumps respectively. While liquid flow meter for hplc pump flow sensors typically require two pressure transducers for each flow line, the inventive fluidic cross pressure transducer arrangement allows the fluidic cross transducer to be used by each respective flow line.
The use of a common fluidic cross transducer at the fluidic cross eliminates the need for four pressure transducers. In another illustrative embodiment of the invention, an apparatus for delivering a liquid in a capillary system includes two flow-source pumps and two associated thermal sensors. Advantages of the invention include correction of the flow output of a typical, analytical-scale 0.
The present invention permits retrofitting and reuse of existing pump technology providing cost and supply advantages. A further advantage of the inventive apparatus and method is there are significant advantages liquid flow meter for hplc pump reusing existing pump technology with the flow correcting apparatus according to the invention.
These advantages include cost savings associated with development, sales and service training and inventory management. Furthermore, traditional constant-flow HPLC pumps are ideally suited for use according to the invention.
Another further advantage of the inventive apparatus and method is because constant flow pumps are used, calibration of the flow sensors can be accomplished easily by flowing know flow rates through the sensors to determine their response. This calibration routine according to the invention can be done at relatively low pressures where pump leakage and solvent compressibility is not an issue, and steady open-loop flow delivery can be expected.
Because a known flow rate is being delivered by the constant-flow pumps, the error between this delivered flow and the flow measured by the flow sensors can be used to diagnose pump leakages. Intelligence can be implemented according to the invention to correlate flow error with the pump cycle to identify where leakages were occurring. Liquid flow meter for hplc pump, this level of diagnostics is extremely useful not only for troubleshooting pump failure, but early diagnosis and suggested corrective action to prevent pump failure.
A further advantage of the inventive method and apparatus is continuous flow operation is possible using typical constant-flow HPLC flow sources. Advantageously, all limitations resulting from stop-flow conditions can be avoided.
The foregoing liquid flow meter for hplc pump other features and advantages of the present invention will be more fully understood from the following detailed description of illustrative embodiments, taken in conjunction with the accompanying drawing in which:. Detailed embodiments of the present invention are liquid flow meter for hplc pump herein, however, it is to be understood that the disclosed embodiments are merely exemplary of the invention, which may be embodied in various forms.
Therefore, specific functional details disclosed herein are not to be interpreted as limiting, but merely as a basis for the claims and as a representative basis for teaching one skilled in the art to variously employ the present invention in virtually any appropriately detailed embodiment.
Some embodiments of the liquid flow meter for hplc pump involve one or more flow sources. For example, one type of flow source includes a piston that displaces a volume of fluid per unit of time. A particular value of volume per unit of time is determined, for example, by controlling the linear velocity of the piston, and by selecting a piston diameter, in the case of liquid flow meter for hplc pump piston having a circular cross-section. Thus, for example, the velocity of the piston multiplied by the area defines a volumetric flow rate.
This flow rate is analogous to, for example, a current source in an electrical circuit, which provides an amount of charge per unit of time. A flow source is distinct from a pressure source, such as a pneumatic air supply with a regulator.
A pressure source is analogous to, for example, a voltage in an electrical circuit. Pressure voltage, in the analogy induces a particular flow rate a current in the analogy if impressed upon a fluid restriction a resistor, in the analogy. Thus, while a flow source has the ability to independently determine a flow rate, a pressure source typically does not independently determine a flow rate. Rather, a pressure source works in cooperation with other component s of a flow path, such as a flow-restrictor component, to determine a flow rate through the flow path.
A first pump and a second pumpwhich are flow-source pumps such as, for example, analytical-scale constant flow-source HPLC pumps. Depending on the pump architecture, change required to enable low-flow delivery involves modifying the gearing of the pump drive mechanism.
These modifications to the gearing of the pump drive mechanism offer a higher incremental drive resolution. This increased resolution allows low-flow operation. While it may be possible to develop a pump specifically designed to deliver flow compatible with nano-scale LC, there are significant cost and supply advantages to reusing existing pump technology with the flow correcting apparatus described above.
Advantageously, traditional constant-flow HPLC pumps are ideally suited for this application. With further reference to FIG. The first inline sensor in a first illustrative embodiment is a delta-P type pressure transducer. It is contemplated within the scope of the invention that any flow sensors capable of providing precise and accurate output signals in the micro-scale flow range can be used to implement the flow sensing according to the illustrative embodiment of the invention.
In particular, it is contemplated within the scope liquid flow meter for hplc pump the invention that other types of flow sensors may be used including but not limited to thermal-based flow sensors, available from, for example, Bronkhorst High-Tech B.
As shown in FIG. The first inline sensor is in fluid communication with a first restriction element The first restriction element is in fluid communication with a liquid flow meter for hplc pump cross In a second operating paththe second pump is in fluid communication with a second inline sensor The second liquid flow meter for hplc pump sensor in the first illustrative embodiment is a pressure transducer.
The second inline sensor is in fluid communication with a second restriction element The second restriction element is in fluid communication with the fluidic cross