Method and apparatus for measuring fluid flow

Measuring and testing – Volume or rate of flow – By measuring transit time of tracer or tag

Reexamination Certificate

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C073S204140, C356S028000

Reexamination Certificate

active

06530286

ABSTRACT:

FIELD OF THE INVENTION
The present invention generally relates to the detection and measurement of fluid flow rates. More specifically, the present invention is directed to a method particularly adapted for measuring ultra low flows. Additionally, the present invention includes an apparatus useful for measuring ultra low flows in devices such as liquid chromatography columns.
BACKGROUND OF THE INVENTION
Ultra low flow rates of liquids are difficult to detect and measure. However, many state of the art applications and devices now require the use of flow rates that are extremely low. For example, in the course of liquid chromatography (LC) it is necessary to move a liquid through the stationary phase of the column, which is generally accomplished through the use of a wide variety of pumps. In classical high performance liquid chromatography (HPLC), a mechanical pump is commonly used that utilizes a reciprocating piston and check valves. This pumping can work very well down to milliliter per minute flow rates. At lower flow rates, however, the accuracy and precision of the flow can become wildly inaccurate and inconsistent due to a wide variety of factors.
As the state-of-the-art in chromatography is pushed into new realms of performance, the flow rate and size of the chromatography media becomes smaller. We now see needs for flow rates that are in the submilliliter per minute range. In fact, flows as small as 10 nanoliters per minute are becoming necessary. It is extremely difficult to accurately and precisely pump such low flow rates without having an absolute measurement of the flow rate coming out of the pump. Conventional “open loop” indirect methods of determining the flow, however, are subject to many errors, including leakage of liquid around the sealing surface of the piston seal, leakage around the fittings for the tubing, compression of the solvent due to variation in the backpressure on the system, accuracy of the movement of the piston due to friction in the mechanical assembly, and reproducible movement in the check valve during the refill stroke of the system (in the case of multiple stroke piston pumping). Most of these factors can be carefully reduced but not eliminated, and all are subject to change as wear affects the performance of the pump, thus leading to poor precision.
One method for measuring the flow of a moving liquid in a laminar flow cell is to measure the movement of an input, such as a particle, into the liquid. The use of an input particle has certain difficulties, however, since it is often difficult to introduce particles into the flowing stream. Another input parameter that has been used to measure fluid flow rates is the application of constant heat from a resistive heating element to the liquid in a tube at a spot in the fluid flow, then measurement of the temperature of the liquid at a sensor downstream from that point. The cooling effect of the tube produces a decrease in temperature that is proportional to the flow rate for a given liquid, and which is related to the heat retention properties of the given liquid. However, this technology suffers a variety of problems. For example, when using this method to regulate the pumping of a gradient of solvent through a chromatography column, the heat capacity of the solvent constantly changes, which undesirably affects the measured temperature of liquid at the sensor, and accordingly distorts the flow rate measurement.
Accordingly, there remains a need to provide a new and improved method and apparatus for measuring fluid flow rates, and ultra low flow rates in particular. The present invention is directed to meeting these needs.
SUMMARY OF THE INVENTION
It is an object of the present invention to provide a new and useful apparatus for measuring fluid flow rates.
It is another object to provide an inexpensive apparatus particularly adapted to measuring extremely low flow rates of a fluid.
It is yet another object to provide an apparatus useful for measuring ultra low flow rates that can be easily incorporated into existing equipment.
Another object of the present invention is to provide a simple and efficient method for measuring flow rates of a fluid.
A still further object is to provide a method for measuring fluid flow rates that can be used with an apparatus according to the present invention.
Yet another object is to provide a liquid chromatography device incorporating the apparatus of the present invention for measuring fluid flow rates therein.
According to the present invention, a method for detecting and measuring flow of a fluid along a flow path is provided. The method comprises moving the fluid in a downstream direction along a flow path, altering the temperature of the fluid at a selected location for a selected duration so as to generate a pulse in the fluid having a leading edge forming a first temperature gradient and a trailing edge forming a second temperature gradient, and monitoring the fluid at a sensing region that is spaced apart and downstream of the selected location, thereby to detect the pulse passing through the sensing region.
The step of altering the temperature of the fluid may be accomplished by heating the fluid at the selected location, such as by transmitting electromagnetic radiation of a selected frequency into the fluid, by passing electrical current through a resistive element that is proximate to the selected location, or by acoustically vibrating the fluid. The selected duration is preferably between 10% and 20% of the time between the step of altering the temperature and the time at which the pulse is detected. The step of altering the temperature is preferably repeated so as to generate a plurality of pulses in the fluid. The step of monitoring the fluid may be accomplished by measuring a relative temperature of the fluid using a sensor element, such as a thermistor, or by measuring the refractive index of the fluid. The pulse may be detected as a temperature gradient indicative of the pulse, such as the first temperature gradient or the second temperature gradient formed during the step of altering the temperature of the fluid.
The method may further include the step of altering a signal from the sensor element, such as by analog to digital conversion or by analog amplification, and further by bandpass filtering the signal. A flow rate of the fluid may be calculated by dividing a known volume of the fluid, in particular the volume of fluid between the selected location and the sensing region, by a time interval measured from the step of altering the temperature to detection of the pulse. A thermal lag interval may be subtracted from the time interval.
The present invention also provides an apparatus for detecting and measuring a flow rate of a fluid. The apparatus comprises a conduit sized and adapted to receive a selected volume of the fluid, a sensor element disposed in the conduit, an energy source proximate to the conduit and operative to transmit energy through a portion of a sidewall of the conduit at a spaced apart location from the sensor element, and a controller operative to generate an on signal and an off signal. The on signal is operative to activate the energy source for a first selected duration, and the off signal is operative to deactivate the energy source for a second selected duration.
The portion of the sidewall may be transparent, and the energy source operative to transmit electromagnetic radiation therethrough. The surrounding sidewall may further include an energy-absorbing portion proximate to the spaced apart location, and an energy-reflecting portion adjacent the energy absorbing portion. The energy source may be a light emitting diode, a LASER, a tungsten bulb, and the like, and may further include a lens operative to focus the electromagnetic radiation. The energy source may alternatively be a resistive element, such as a nichrome wire or a polyimide backed heating element. The sensor element may be a thermistor, or the like. The on signal and off signal may be intermittently generated by said controller so as to form a plu

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