Abstract:
There is described a method and apparatus for measuring temperature of a fluid in a microchannel of the type having spaced walls. An ultrasonic transducer transmits ultrasonic waves transmitted from one wall to the opposite wall. A processor determines the time-of-flight of the ultrasonic waves from the one wall and reflected to the opposite wall to the one wall. The processor converts the time-of-flight to velocity by dividing the distance between walls by the time-of-flight. The processor converts velocity to temperature from the relationship of velocity to temperature in the fluid.

Description:
RELATED APPLICATIONS  
       [0001]    This application claims priority to Provisional Application Serial No. 60/309,245 filed Jul. 31, 2001. 
     
    
     GOVERNMENT SUPPORT  
       [0002] This invention was made with Government support under Contract No. N66001-00-C-8077 awarded by the Navy. The Government has certain rights in this invention. 
     
    
     
       BRIEF DESCRIPTIONS OF THE INVENTION  
         [0003]    This invention relates generally to microfluidic devices having microfluidic channels with integrated ultrasonic transducers for measuring the temperature of fluids in said channels and more particularly to such devices employing ultrasonic transducers such as integrated micromachined ultrasonic transducers (MUTs) or piezoelectric transducers.  
         BACKGROUND OF THE INVENTION  
         [0004]    The large investments in the microelectronics industry converted integrated circuits laboratories into machine shops where miniature electromechanical systems are designed and built. Electromechanical as well as electro-optical systems have been miniaturized and used in many different applications. In the same fashion, miniaturization is presently applied in the field of microfluidics. Microfluidics technology provides the advantage of being able to perform chemical and biochemical reactions and/or separations with high throughput low volumes. Microfluidic systems employ microchannels formed in substrates or chips in which chemical and biochemical materials are transported, mixed, separated and tested.  
           [0005]    One of the parameters measured such microfluidic systems is the temperature of the fluids and the change in temperature of fluids as a result of any reactions carried out in the channel.  
           [0006]    A typical method for temperature measurement involves using a thermocouple embedded in the substrate, preferably close to the fluidic channel. However, this method measures the average temperature of the substrate and fluid. In most cases, the channel is so small that the thermocouple reading is dictated primarily by the substrate temperature.  
           [0007]    There is a need for directly measuring the temperature of fluids in microchannels.  
         OBJECTS AND SUMMARY OF THE INVENTION  
         [0008]    It is an object of the present invention to provide a system and method for measuring the temperature of fluids in a channel using ultrasonic transducers.  
           [0009]    It is another object of the present invention to provide a system for measuring the temperature of fluids in a channel using integrated ultrasonic transducers such as micromachined capacitive or piezoelectric transducers.  
           [0010]    Micromachining permits fabrication of ultrasonic transducers having sizes compatible with the microchannels of microfluidic devices. Furthermore, the transducers can be integrated into the microchannels. Capacitive micromachined ultrasonic transducers (cMUTs) operating both in air and water are known and described in U.S. Pat. Nos. 5,619,476; 5,870,351 and 5,894,452. In both air and water, a Mason electrical equivalent circuit is used to represent the transducers and predict their behavior (W. P. Mason,  Electromechanical Transducers and Wave Filters  (Van Nostrand, N.Y.,  1942 )). These transducers are fabricated using standard IC processes and have been integrated with signal processing electronics to form an integrated system. In the article entitled “Highly Integrated 2-D Capacitive Micromachined Ultrasonic Transducers” appearing in IEEE Ultrasonic Symposium Proceedings pp. 1163-1666, 1999, S. Calmes et al., describe the fabrication of cMUTs with through wafer connections so that they can be flip-chip bonded to chips having signal processing electronics. Alternatively, the processing electronics can be implemented on the same silicon wafer avoiding the through wafer via structure. The dynamic range and bandwidth of cMUTs surpass their piezoelectric counterparts while being completely compatible with microfluidic chip fabrication processes.  
           [0011]    Capacitive micromachined ultrasonic transducers (cMUTs) with dimensions of 100 μm or less are fabricated on the walls of the fluidic channels and operate in the 1-100 MHz frequency range. The cMUTs are surface micromachined to have a low surface profile, permitting undisturbed fluid flow. These transducers enable in-situ measurements of temperature of the fluid in the channel by measuring the velocity and/or attenuation of sound waves in the fluid in the channel.  
           [0012]    Ultrasonic transducers having the above-described characteristics can also be micromachined from piezoelectric material. They may be formed by thin film deposition such as sputtering, sol-gel deposition or other types of physical or chemical deposition. Through wafer interconnects can be used with piezoelectric transducers.  
           [0013]    The present invention provides a temperature measuring system in which ultrasonic transducers fabricated in one wall of the channel or placed on the substrate opposite the channel generate ultrasonic waves which reflect from one or both walls of the channel and provide an output signal representative of the velocity of the sound waves or attenuation or both in the fluid. The signals are then processed to provide the fluid temperature. 
       
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0014]    [0014]FIG. 1 is a perspective view of a portion of a microfluidic channel including an ultrasonic transducer and signal processing electronics connected to the transducer by through wafer connections.  
         [0015]    [0015]FIG. 2 is a sectional view of the microfluidic device of FIG. 1 including a top cover to form a channel and taken generally along the line  2 - 2  of FIG. 1.  
         [0016]    [0016]FIG. 3 is a sectional view of a microfluidic channel with the cMUT mounted on the bottom of the device substrate and including signal processing electronics connected to the ultrasonic transducer.  
         [0017]    FIGS.  4 A- 4 C show the generation of ultra sonic pulses applied to the transducers of FIG. 1 or  3  and the reflected waves from the interfaces or walls of the microfluidic channel.  
         [0018]    [0018]FIG. 5 is a typical oscilloscope trace showing a first pulse as applied to the transducer or as reflected on the bottom of the microfluidic channel in FIG. 3 and the pulse reflected from the top wall of the microfluidic channel.  
         [0019]    [0019]FIG. 6 shows acoustical velocity in distilled water as a function of temperature.  
         [0020]    [0020]FIG. 7 shows attenuation in distilled water as a function of temperature.  
         [0021]    [0021]FIG. 8 schematically shows a processing circuit for measuring phase differences between reflected pulses.  
     
    
     DESCRIPTION OF PREFERRED EMBODIMENTS  
       [0022]    The ultrasonic transducer  10  shown in FIG. 1 comprises a cMUT  11  which includes a plurality of cells  12 . Each cell is made of vacuum-sealed fully supported membrane with a diameter of 5-200 micrometers. For example a 100 micrometer square transducer with individual cells 20 micrometers in diameter could be made with 25 small membranes. A detailed description of the method of fabrication and operation of cMUTs is found in U.S. Pat. Nos. 5,619,476; 5,870,351 and 5,894,452 incorporated herein in their entirety by reference.  
         [0023]    In microfluidic technology, the chemical or biochemical reactions and/or separations take place in microchannels having dimensions in the range of 1 micron to 500 microns or more. Ultrasonic waves are ideal for measuring the temperature of fluids in the channel. In accordance with one embodiment of the present invention, a cMUT  11  is integrated into the walls of the microchannel, FIGS. 1 and 2, or affixed to the wall of the microfluidic device substrate, FIG. 3. In another embodiment of the present invention, the ultrasonic transducer  10  comprises a micromachined piezoelectric transducer fabricated as described above.  
         [0024]    Referring to FIGS. 1 and 2, a microchannel  13  is shown in the top  14  of a microfluidic device  16 . The microchannel can, for example, have dimensions  1  micron to 500 microns or more depending upon the application of the device. The channels can be formed by micromachining a groove  17  in the top plate  14  and suitably sealing the top plate to the bottom substrate  18 . The top plate  14  can be glass, silicon or the like in which the groove is machined, or it can be a polymetric material which can be machined or molded with the groove  17 . In accordance with one embodiment of the present invention the bottom substrate  18  is a semiconductor material such as silicon which is processed as described above to form the integrated cMUT  11 . The top surface of the CMUT is substantially co-extensive with the bottom wall of the channel  13 . This minimizes the influence of the CMUT on the fluid flow. The cMUT can be connected to known excitation and detector electronics  21  using through device leads  22  and flip-chip bonding techniques to bond the integrated detector electronics  21 . Such techniques are described in Oralkan (O. Oralkan, X C. Gin, F. L. Degertekin and B. T. Khuri-Yakub, “Simulation and experimental characterization of a #2-D CMUT array element, IEEE TRANS. UFFC, 46, pages 1337-40, 1999).  
         [0025]    Alternatively cMUT may be formed in or attached to the bottom of the substrate  18  as shown in FIG. 3. In still another embodiment, the ultrasonic transducer is a piezoelectric material which is deposited in the channel or on the bottom of the substrate. The substrate can be any material such as glass, plastic, etc., since the transducer is formed by deposition.  
         [0026]    In accordance with the present invention the ultrasonic transducer  10  is used to measure velocity and/or attenuation of sound waves traveling through the liquid flowing along the microchannel. The sound velocity or attenuation can be converted to temperature by using a calibration curve, which relates the liquid temperature to the acoustic properties of the liquid. This technique can be used to determine the temperature of the fluid in the channel and temperature of chemical reactions occurring inside the microfluidic channels.  
         [0027]    The acoustic properties of liquid change dramatically with temperature. FIGS. 4 and 5 show the value of sound velocity and attenuation respectively at different temperatures for pure water.  
         [0028]    [0028]FIGS. 1 and 3 show a pulser  21  which generates pulses such as the pulses  21 , FIG. 4A, which are applied to the cMUT, FIG. 4B, which causes the cMUT to resonate and generate the acoustic waves designated by the numeral  1 , FIG. 4C. The operating frequency is determined by the size of the cells and the spacing of the membrane from the substrate in each of the cells. The transducer causes mechanical displacement which launches the acoustic waves, FIG. 4C. When a piezoelectric ultrasonic transducer is employed, the generation of acoustic waves is well known. In FIG. 1 the waves are launched directly through the fluid flowing in the channel whereas in FIG. 3 the waves are launched through the substrate and through the channel  13 . Referring to FIG. 2, the acoustic waves reflect from the upper wall of the channel and are received by the transducer as shown by the numeral  2 , FIG. 4C. The input signal  1  and reflected signal  2  are received by a receiver  23 . The signals are applied to an analog digital converter  24  and then to a processor  26 . Referring to FIG. 4C, additional reflections from various other surfaces are shown as pulses  3  and  4 . Referring to FIG. 5 a typical input wave obtained by an oscilloscope is shown at  31  while the first reflective wave is shown at  32 . In this illustration a time lapse for travel of the sonic wave to the upper wall and return is 298 nanoseconds. The processor may count the lapsed time between the emitted and reflected wave, or if the waves are quite close, a processing circuit such as that shown in FIG. 8 may be incorporated in the processor. The processing circuit, FIG. 8, includes fast Fourier transforms  36  and  37  and phase discriminator  38  which provides the phase difference between the launched wave  31  and return wave  32 . This is then converted to elapsed time. The elapsed time can be converted to velocity by the following equation:  
       v   =       2      h       Δ                 t                             
 
         [0029]    where h is the channel height and At is the time separation or lapse between two pulses. For example, if the channel height is 223 microns using the delay of 298 nanoseconds with pure water inside the channel and using the relationship shown in FIG. 6, the fluid temperature is calculated to be  25 ° C. As explained above if the two pulses are not well separated it is possible to measure the delay using the spectrum of two or more pulses having minimas separated by Δt. The separation of these minimum points is given by Δf=1/Δt provided that the pulses have the same amplitude and phase. The time-of-flight, and consequently the sound velocity within the channel, can be determined by measuring the frequency separation. Sound velocity can then be used to measure or monitor the fluid temperature. More accurate evaluations may involve a simulation program which calculates the phase and amplitude of acoustic pulses after propagating through the glass and liquid.  
         [0030]    The present method is substantially immune to substrate temperature fluctuations since the relative delay between pulses reflecting from the bottom and top of the channel is measured. Thus, there has been provided a novel method and apparatus for measuring temperature of fluids in microfluidic channels.