Abstract:
A method to deliver medication. The apparatus has an acoustic volume sensor that acoustically excites a reference volume and variable-volume chamber with an acoustic source and measures the acoustic response with microphones acoustically coupled to the reference and the variable-volume chamber. A disposable drug cassette is coupled to the acoustic volume sensor and includes a drug reservoir and valve. The method includes receiving a volume signal and inputs from a user input or a second sensor and controlling the valve based on these inputs.

Description:
RELATED APPLICATIONS 
     The present application is a Continuation of U.S. patent application Ser. No. 13/968,710, filed Aug. 16, 2013 and entitled “Metering System and Methods for Aerosol Delivery”, which is a Continuation of Application of U.S. patent application Ser. No. 12/897,100, filed Oct. 4, 2010 and entitled “Metering System and Method for Aerosol Delivery”, now U.S. Pat. No. 8,511,299, issued Aug. 20, 2013, which is a Continuation Application of U.S. patent application Ser. No. 11/942,883, filed Nov. 20, 2007 and entitled “Method System and Method for Aerosol Delivery”, now U.S. Pat. No. 7,806,116, issued Oct. 5, 2010, which is a Continuation of U.S. patent application Ser. No. 10/670,641, filed Sep. 25, 2003 and entitled “Metering System and Method for Aerosol Delivery”, now U.S. Pat. No. 7,305,984, issued Dec. 11, 2007, all of which are hereby incorporated herein by reference in their entireties. 
     Additionally, the present application contains subject matter related to that of U.S. patent application Ser. No. 10/675,278, filed Sep. 30, 2003 and entitled “Detection System and Method for Aerosol Delivery”, now U.S. Pat. No. 7,342,660, issued Mar. 11, 2008; U.S. patent application Ser. No. 10/670,977, filed Sep. 25, 2003 and entitled “System and Method for Improved Volume Measurement,” now U.S. Pat. No. 7,066,029, issued Jun. 27, 2006; U.S. patent application Ser. No. 10/671,278, filed Sep. 25, 2003 and entitled “System and Method for Aerosol Delivery,” now U.S. Pat. No. 7,021,560, issued Apr. 4, 2006; and U.S. patent application Ser. No. 10/670,924, filed Sep. 25, 2003 and entitled “Valve System and Method for Aerosol Drug Delivery,” now U.S. Pat. No. 7,146,977, issued Dec. 12, 2006. The disclosures of the foregoing are incorporated herein by reference. 
    
    
     FIELD OF THE INVENTION 
     The present invention generally relates to systems and methods for metering and outputting quantities of aerosolized substances. More particularly, embodiments of the present invention can relate to systems and methods for accurately delivering atomized drugs. 
     BACKGROUND 
     Aerosolized drugs for inhalation are considered reasonable alternatives to injections or other types of drug-delivery systems, such as intravenous delivery, subcutaneous injection, and intra-muscular. For example, insulin can be delivered by inhaling an aerosolized form, thus sparing a patient pain and inconvenience caused by subcutaneous injection of insulin. 
     Inhaling aerosols, however, typically lacks the accuracy of injections, and so is inappropriate for use in situations where accurate dosing is critical. With aerosolized drugs, the proper amount required for delivery is often not properly metered for delivery. For example, asthma inhalers typically have an acceptable accuracy of plus or minus 25% of the nominal dose. For systemic drug delivery of insulin, on the other hand, such a level of accuracy is considered too unpredictable to allow for appropriate use, even though aerosolized delivery is much less harmful to a patient than intravenous delivery. 
     Thus, a need exists for accurately and predictably delivering a predetermined dose of aerosolized drugs. 
     SUMMARY OF THE INVENTION 
     An embodiment comprises a variable acoustic source and a microphone, both acoustically coupled to a volume that is divided into an air region and a fluid region. A processor is configured to receive a signal from the microphone, and to determine a volume of the air region. A fluid valve is configured to allow an amount of fluid to exit the fluid region, the amount of fluid being associated with the volume of the air region. An atomizer is coupled to the fluid region, and is configured to aerosolize at least a portion of the amount of fluid. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  is a schematic diagram of a system for outputting an aerosol, according to an embodiment of the invention. 
         FIG. 2  is a schematic diagram of a system for outputting an aerosol, according to an embodiment of the invention in the context of aerosolized drug delivery. 
         FIG. 3  is a schematic diagram of acoustic volume sensors that can be used with three embodiments of the invention. 
         FIG. 4  is a schematic diagram of an acoustic volume sensor according to an embodiment of the invention. 
         FIGS. 5A-5C  is a schematic diagram of a number of acoustic volume sensors that further describe and explain embodiments of the invention. 
         FIG. 6  is a schematic diagram of a mechanical analog to the system according to an embodiment of the invention. 
         FIG. 7  is a cutaway view of a detachable cassette for which a volume determination can be made, according to an embodiment of the invention. 
         FIG. 8  is a top view of a detachable cassette for which a volume determination can be made, according to an embodiment of the invention. 
         FIG. 9  is a schematic diagram of a signal processing technique according to an embodiment of the invention. 
         FIG. 10  is a flow chart of the signal processing technique illustrated in  FIG. 9 . 
         FIG. 11  is a schematic diagram of a signal processing technique according to an embodiment of the invention. 
         FIG. 12  is a flow chart of the signal processing technique illustrated in  FIG. 11 . 
         FIG. 13  is a schematic diagram of a signal processing technique using a speaker impulse, according to an embodiment of the invention. 
         FIG. 14  is a flow chart of the signal processing technique illustrated in  FIG. 13 . 
         FIG. 15  is a schematic diagram of an embodiment of the invention that does not require the presence of an acoustic port. 
         FIG. 16  is a schematic diagram of a low-frequency approximation of an acoustic volume sensor, according to an embodiment of the invention. 
         FIG. 17  is a schematic diagram of a high-frequency approximation of an acoustic volume sensor, according to an embodiment of the invention. 
         FIG. 18  is a flow chart of a signal processing technique using amplitude ratio measurements, according to an embodiment of the invention. 
     
    
    
     DETAILED DESCRIPTION 
     Embodiments of the invention include systems and methods for outputting an aerosol. For purposes of this application, the term aerosol includes airflows containing particles, such as aerosolized liquids, powders, and combinations of the two.  FIG. 1  displays a schematic overview of a system for outputting an aerosol, according to an embodiment of the invention. In this embodiment, variable acoustic source  101  and microphone  102  are acoustically coupled to chamber  103 . Volume  103  is divided into air region  103   a  and fluid region  103   b . For purposes of this application, the term air includes any gas or combination of gases. 
     Processor  104  is configured to receive a signal from microphone  102 , and to determine a volume of air region  103   a . Processor  104  is in communication with fluid valve  105 , and is configured to send a control signal to fluid valve  105  to open and close fluid valve  105  to allow an amount of fluid out from fluid region  103   b  into target region  106 . The amount of fluid released into target region  106  is associated with the determined volume of air region  103   a . In one embodiment, chamber  103  is a fixed volume, and so the volume of fluid released into target region  106  is substantially identical to a determined change in volume of air region  103   a . Target region  106  is coupled to atomizer  107 , which is configured to aerosolize at least a portion of the fluid that has exited fluid region  103   b.    
     In one embodiment, the system includes a second processor  119  that is configured to calculate a volume of the aerosolized fluid, and is further configured to output a volume signal associated with the calculated volume. In this embodiment, the amount of fluid allowed to enter target region  106  is associated both with the volume of air region  103   a  and with the aerosol volume. 
     The second processor is configured to receive a signal from volume sensor  108  in communication with aerosol flow chamber  111 . Volume sensor  108  can be any combination of hardware and software configured to collect information for determining aerosol volume. For the purposes of the invention, the terms pressure, air flow and flow rate are all used interchangeably, depending on the context. 
     The second processor is not shown in  FIG. 1 , and for the purposes of the invention, processor  104  and the second processor can be the same processor, or can be separate from each other. For the purposes of the invention, the term processor includes, for example, any combination of hardware, computer programs, software, firmware and digital logical processors capable of processing input, executing algorithms, and generating output as necessary to practice embodiments of the present invention. The term processor can include any combination of such processors, and may include a microprocessor, an Application Specific Integrated Circuit (ASIC), and state machines. Such a processor can include, or can be in communication with, a processor readable medium that stores instructions that, when executed by the processor, causes the processor to perform the steps described herein as carried out, or assisted, by a processor. 
     For the purposes of the invention, “processor readable medium,” or simply “medium,” includes but is not limited to, electronic, optical, magnetic, or other storage or transmission devices capable of providing a processor with processor readable instructions. Other examples of suitable media include, but are not limited to, a floppy disk, CD-ROM, magnetic disk, memory chip, ROM, RAM, ASIC, configured processor, all optical media, all magnetic tape or other magnetic media, or any other medium from which a processor can read. Also, various other forms of processor readable media may transmit or carry instructions to a computer, including a router, private or public network, or other transmission device or channel. Also, various other forms of processor readable media may transmit or carry instructions to a computer, including a router, private or public network, or other transmission device or channel. 
     Target region  106  is coupled to air valve  109  and air source  110 . Processor  104  can be further configured to send a control signal to air valve  109  to open and close air valve  109 , thereby selectively exposing air source  110  to target region  106  and to atomizer  107 . Air source  110  can be a compressed air source or liquefied air source, an air source open to the atmosphere, or any air source useful for moving fluid from target region  106  to atomizer  107 , and/or for purging target region  106 . In one alternative embodiment, air source  110  may comprise a volume containing an amount of liquefied propellant gas, where air valve  109  is configured in such a way as to connect to the portion of the volume typically containing vapor. 
     In one preferred embodiment, air source  110  is connected to target region  106  through air valve  109  in close proximity to fluid valve  105 . Thus, when air valve  109  is opened, air from air source  110  will push a substantial portion of the volume of fluid in target region  106  toward the physical gap  112  in closed volume  113  and then to atomizer  107 . Additionally, if the internal diameter of target region  106  is comparatively narrow, such as in a small bore capillary, utilizing air from air source  110  to push the volume of fluid in target region  106  toward atomizer  107  may have the additional advantages of reducing or eliminating blockage of the system, such as crystal growth, and biological contamination that could result from fluid remaining otherwise remain in target region  106  and improving accuracy of the system by ensuring that a substantial portion of the fluid exits target region  106  toward atomizer  107 . 
       FIG. 2  is a schematic diagram of a system for outputting an aerosol, according to an embodiment of the invention, in the context of aerosolized drug delivery. In this embodiment, acoustic volume sensor  201  is coupled to disposable drug cassette  202 . Pressure source  203  is coupled to acoustic volume sensor  201  to assist in outputting the drug from acoustic volume sensor  201  to disposable cassette  202 . Disposable cassette  202  includes drug reservoir  202   a , valve  202   b  and atomizer  202   c , and is detachably coupled to acoustic volume sensor  201 . Atomizer  202   c  can be, for example, an electro-hydrodynamic atomizer. Processor  204  is coupled to acoustic volume sensor  201  to calculate an amount of drug to output from drug reservoir  202   a , and to control valve  202   b.    
     Atomizer  202   c  is coupled to air flow sensor system  205 . Air flow sensor system  205  can be any known system for measuring air flow or pressure of the aerosolized drug to be output to a patient. For example, air flow sensor system  205  can include an anemometer, a pin-wheel sensor, or any other sensor operable to measure air flow, flow rate or pressure. In the embodiment shown, air flow sensor system  205  is a light scatter detection system that includes light source  205   a , light detector  205   b , and pressure sensor  205   c . Processor  204  is coupled to light source  205   a , light detector  205   b  and pressure sensor  205   c . Processor  204  is configured to receive a light detection signal  205   b  and pressure or air flow signal from pressure sensor  205   c , and calculate the aerosol volume inside air flow sensor system  205 . As stated above, this system is described in detail in U.S. patent application Ser. No. 10/670,655, titled “Detection System and Method for Aerosol Delivery.” 
     Processor  204  is further coupled to power  206  to power the atomizer on and off at the appropriate time.  FIG. 3  is a schematic diagram of acoustic volume sensors that can be used with three embodiments of the invention. In each embodiment, the chamber has volume V 1 , and is acoustically coupled to port M 1  to form an acoustic system. Microphone  301  (or other suitable acousto-electrical transducer) and an acoustic source  302 , such as a speaker, (or other suitable electro-acoustical transducer) are acoustically coupled to this acoustic system. The electrical output of the microphone is placed in communication with electrical input of acoustic source  302 , in such a way that the amplitude and phase relationships of the signals promote acoustic resonance of the system. A measurement of a quantity related to the system&#39;s resonant frequency can permit determination of the chamber volume, as is described in U.S. Pat. No. 5,349,852, incorporated herein in its entirety. Such a resonance frequency measurement can be achieved in a processor. Alternatively, an additional chamber of known volume, configured with a port in a manner similar to one of the embodiments of  FIG. 3 , may be employed to produce a resonance, and a quantity related to the resonant frequency may be measured. This can, in turn, lead to a determination of the relevant volume. 
     In embodiment (1) of  FIG. 3 , microphone  301  is placed within the chamber, and acoustic source  302  forms a portion of the wall of the chamber. Because the resonance determination does not require that the chamber be sealed in the fashion required for acoustic-pressure type systems, the transducers employed in these embodiments do not need to be located in the chamber forming part of the system. It is necessary only that the transducers be acoustically coupled to the system. 
     In embodiments (2) and (3) of  FIG. 3 , a second volume V 2  is associated with the system and is coupled to volume V 1  via port M 1 . In each of embodiments (2) and (3), acoustic source  302  forms a portion of the wall of volume V 2 , and can be, for example, a piezoelectric speaker. In embodiment (2), microphone  301 , which can be, for example, of the velocity type, forms a part of the wall between volumes V 1  and V 2 , and responds only to differences in pressure between the two volumes; because the pressure difference between the two volumes tends to be near zero at frequencies below the frequency of natural resonance of the system, noise in microphone  301  is effectively canceled out. In embodiment (3), microphone  301  is disposed in volume V 2 . 
       FIG. 4  is a schematic diagram of an acoustic volume sensor according to an embodiment of the invention. In this embodiment, acoustic volume sensor enclosure  400  includes first volume  401  and second volume  402 , separated by printed circuit board  403 . First microphone  404  is acoustically coupled to first volume  401 , and second microphone  405  is acoustically coupled to second volume  402 . 
     Printed circuit board  403  contains an acoustic source, which can be, for example, a piezoelectric speaker. In one embodiment, one or both of first microphone  404  and second microphone  405  is attached to printed circuit board  403 . Printed circuit board  403  can include, in one embodiment, an inner layer configured to pass electrical signals. Printed circuit board  403  is coupled to acoustic volume sensor enclosure  400  in a way that forms a substantially air-tight seal. In one embodiment, printed circuit board  403  includes a hole to equalize pressure between the first volume and the second volume. In this embodiment, the hole is small enough so as to not adversely impact the acoustic qualities of the system. 
     First microphone  404  and second microphone  405  are coupled to a processor (not shown). This processor is configured to receive a signal from the microphones, and is further configured to determine a volume of the variable-volume chamber based on the received signals. In one embodiment, the processor is contained on printed circuit board  403 . 
     Second volume  402  is coupled to third volume  407  via port  408  in such a way as to create an acoustic system including second microphone  405  and acoustic source  406 . Third volume  407  is divided into air portion  407   a  and fluid portion  407   b . In one embodiment, third volume  407  is a detachable cassette. Air portion  407   a  can contain air, or can contain any suitable gas for creating an acoustic resonance for volume determination. Fluid portion  407   b  can include any fluid, including medicine, ink, or any fluid for which a volume measurement is desired. In one embodiment, air portion  407   a  is separated from fluid portion  407   b  by a diaphragm  409 . Diaphragm  409  is configured to allow for a volume measurement of air portion  407   a . Fluid portion  407   b  of third volume  407  includes fluid output fitting  410  for allowing fluid to escape from fluid volume  407   b  in a controlled way. 
     The basic theory behind the acoustic volume sensor according to an embodiment of the invention is that two chambers of air separated by a relatively small tube of air will resonate at a specific frequency when provided with an impulse to either of the air chambers or to the air in the tube that connects the chambers. The resultant resonant frequency is related to the volumes of the chambers, the tube dimensions and miscellaneous parameters of the gas that is used as a medium within the resonator. 
     To ensure a resonance exists as described by the basic theory, some assumptions may be used. First, the wavelength associated with the resonant frequency should be significantly larger than any of the critical dimensions of the resonator. Typically, the free-space wavelength associated with an acoustic wave of the resonant frequency should be approximately 20 times larger than the diameter of the chambers, and also of the length and diameter of the tube. This assumption provides that the air pressure within a given chamber is approximately uniform throughout the volume and that the air in the tube is also at a uniform pressure. Resonators having resonant frequencies with wavelengths less than 20 times the critical dimensions can be designed with acceptable behavior. The applicability of the assumptions, however, and the relevance of the theory will be diminished as the wavelength is decreased (or, conversely, the resonant frequency is increased) for a given resonator design. 
     Second, the energy lost from the resonator should be kept small so that the resonator will be underdamped. The resonator is modeled as a second-order system and the corresponding losses (damping) should be kept small so that the resonance can be readily observed. No widely accepted “rules of thumb” exist to determine the acceptability of various losses. Furthermore, no extensive studies have been performed to determine, without experimentation, the degree of losses that are expected for a given resonator geometry. Most of the losses are believed to be the result of viscous losses to the walls of the tube as the air traverses the tube&#39;s length. 
     Finally, at all frequencies of interest, the acoustic processes should be adiabatic. In other words, the acoustic processes should occur at a rate sufficient to keep heat energy from either leaving the system or equilibrating with the surrounding media. For the purposes of this document, acoustic processes at audible frequencies are always considered to be adiabatic. 
       FIGS. 5A-5C  is a schematic diagram of a number of acoustic volume sensors that further describe and explain embodiments of the invention. All of the following representations are considered equivalent with the only differences being required for practical implementation.  FIG. 5 a    describes a simplified resonator using a piston  501   a  to vary the V 1  volume and excite the system.  FIG. 5 b    replaces the piston with a speaker  501   b  for excitation and incorporates microphones  502   b  and  503   b  for determining the acoustic pressure levels present in the V 0  and V 1  volumes. 
       FIG. 5 c    depicts the implementation details required to utilize the resonator for measurement of volumes that vary as a result of fluid movements using a diaphragm as an interface and valves for control. In this figure, speaker  501   c  is used to excite the system, and microphones  502   c  and  503   c  for determining the acoustic pressure levels present in the V 0  and V 1  volumes. 
     Volume V 2  is acoustically coupled to volume V 1  via port  504   c . Volume V 2  can be detachable from volume V 1  at port  504   c . Volume V 2  includes gas region  505   c  and fluid region  506   c . In one embodiment, fluid region  506   c  can be bounded by delivery input valve  508   c  and patient valve  509   c . Delivery input valve  508   c  is configured to be coupled to a fluid source that allows fluid to flow into the volume for metering upon output. Patient valve  509   c  can be processor controlled to open and close to allow a specific volume of fluid to exit fluid region  506   c.    
     The theoretical acoustic behavior can be modeled using a simple mechanical analog. Air volumes have frequency-dependent performance analogous to springs. Air ports have frequency-dependent performance analogous to masses. Acoustic dampers within air ports have an analogous effect on performance as a frictional surface over which a mass is forced to slide. 
       FIG. 6  is a schematic diagram of a mechanical analog of an acoustic volume sensor according to an embodiment of the invention. In  FIG. 6 , to make the analogy explicit, spring  601  has a spring constant K 0  analogous to the volume V 0 , spring  602  has a spring constant K 1  analogous to volume V 1 , and spring  607  has a spring constant K 2  analogous to volume V 2 . Reference force sensor  603  is analogous to the reference microphone, and front force sensor  604  is analogous to the front microphone. Piston  605  can excite the system in a way analogous to the speaker, driving mass  606  analogously to the air port. 
     Similarly, embodiments of the acoustic volume sensor can be modeled as an electrical circuit (not shown), with capacitors taking the place of springs (or volumes), a current source driving the system in place of the piston (or speaker), and inductors and resistors representing the mass (or port). 
       FIG. 7  is a cutaway view of a detachable cassette for which a volume determination can be made, according to an embodiment of the invention. In this embodiment, housing  701  contains selectable volume  702 , which is divided into air chamber  703  and fluid chamber  704 . Air chamber  703  and fluid chamber  704  are, in one embodiment, separated by a diaphragm. 
     Housing  701  includes air port  705  for coupling to an air source such as a condensed air source. Housing  701  further includes AVS port  706  for acoustically coupling volume  702  to an acoustic volume sensor. 
     In one embodiment, housing  701  can contain multiple selectable volumes  702 , each with a corresponding AVS port  706 , air port  705 , valve  707  and fluid/air path  708 . In one embodiment, one selectable volume  702  can share an AVS port  706 , an air port  705 , a valve  707  and a fluid/air path  708  with another selectable volume  702 . Each selectable volume  702  is configured to be individually selectable for acoustic coupling with an acoustic volume sensor. 
     In one embodiment, fluid chamber  704  is coupled to valve  707  by fluid/air path  708  for outputting a selected amount of fluid from fluid chamber  704 , based on a volume determined in air chamber  703 . Fluid/air path  708  is further configured to be coupled to an air source for purging parts of the system. 
     In one embodiment, valve  707  is configured to be coupled to fluid chamber  704  when fluid chamber  704  is coupled to an acoustic volume sensor. Valve  707  is further configured to be coupled to a processor (not shown), and configured to receive a control signal from the processor to open and close based on a volume determined in air chamber  703 . Valve  707  is configured to be coupled to an atomizer. 
       FIG. 8  is a top view of a detachable cassette for which a volume determination can be made, according to an embodiment of the invention. In this embodiment, the detachable cassette includes 7 selectable volumes, which can be seen from the corresponding air ports  805  and acoustic volume sensor ports  806 . In principle, housing  801  can include any practicable number of selectable volumes. 
     Valve  807  can be seen attached to acoustic volume sensor coupling  809 . Acoustic volume sensor coupling  809  is configured to detachably couple the detachable cassette to a fluid volume sensor in a way that allows any selectable volume to be selectably coupled to an acoustic volume sensor. 
     Acoustic volume sensors can employ a number of signal processing techniques to determine the resonance and volume of a variable volume chamber.  FIGS. 9-23  illustrate several exemplary methods of signal processing. In  FIG. 9 , a speaker is driven with a fixed frequency sinusoid and the phase difference between microphones  901  and  902  is measured. In this embodiment, the microphone outputs are passed through zero-crossing detector  903  to create digital square waves in phase with their analog sine outputs. The two square waves are then passed through an exclusive OR gate, XOR  904 ; the duty cycle of the XOR  904  output, which is proportional to the phase difference, is measured. After determining the phase difference, a different frequency is output from speaker  905 , and the new phase difference is measured. This is repeated until the system finds the frequencies for which the phase difference straddles 90 degrees. Linear interpolation can then be used to calculate the system&#39;s resonant frequency. Phase difference is measured, and the system is controlled, by processor  906 . 
       FIG. 10  is a flow chart describing the steps of acoustic volume sensing using the digital duty-cycle technique illustrated in  FIG. 9 . In one embodiment, at step  1001 , a duty-cycle counter is configured, and transmission to a speaker is initiated. The speaker is configured in this embodiment to output a fixed frequency sinusoidal signal. 
     At step  1002 , counter data is accumulated as the speaker transmission is completed. The phase difference between the two microphones, at step  1003 , is then calculated using the duty cycle of the XOR output using the equation phase (in degrees)=180*duty cycle( 0 - 1 ). 
     Once the phase difference is determined, then at step  1004 , a determination is made as to whether the phase difference is within some predetermined window of 90 degrees. If not, then at step  1005 , the drive frequency is changed to move the phase measurement closer to 90 degrees. If the phase difference is within some predetermined window of 90 degrees, then at step  1006 , the speaker drive frequency is changed so that the next phase measurement is on the other side of 90 degrees. 
     At step  1007 , a determination is made as to whether the last two phase measurements straddle 90 degrees. If not, the system is reset back to step  1001 . If so, then the last two phase measurements (and their corresponding frequencies) are used to calculate the resonant frequency, using a linear interpolation to find the frequency at which the phase difference is 90 degrees. 
     At step  1009 , the temperature of the system is measured. Using the known variables, the relevant volume is measured using the equation (volume=k 1 /((f^2/T)−k 2 ), 
     where k 1  and k 2  are calibration constants (e.g., the physical geometry and molecular properties of the gas), “f” is the calculated resonant frequency, and “T” is the measured temperature in degrees Kelvin. 
       FIG. 11  is a schematic diagram of signal processing techniques according to an embodiment of the invention. The technique illustrated is similar to the technique displayed in  FIG. 9 , except that a voltage-controlled oscillator, or VCO  1106 , is used instead of a processor to generate speaker drive signals, with VCO  1106  input driven by the output from XOR  1104  and then passed through integrator  1105 . In principle, this circuit will automatically find the system&#39;s resonant frequency by locking onto the 90 degree phase difference. The integrator output is only stationary with 50% of the XOR  1104  output duty cycle. The VCO input and output is then altered to maintain a 50% XOR duty cycle. With this technique, an external processor (not shown) can either measure the input voltage to VCO  1106  (with voltage being substantially proportional to frequency), or can measure the frequency of the signal driving speaker  1107 , or can measure the frequencies of microphones  1101  and  1102 , or can measure the output from XOR  1104 . 
       FIG. 12  is a flow chart of the signal processing technique illustrated in  FIG. 11 , according to an embodiment of the invention. In this embodiment, at step  1201 , a frequency measurement counter is configured, possibly using a high-speed timer to measure the frequency output from the VCO, or measured by the microphones. 
     At step  1202  the temperature of the system is measured. Using this information, the volume is calculated using the equation (volume=k 1 /((f^2/T)-k 2 ), where k 1  and k 2  are calibration constants (e.g., the physical geometry and molecular properties of the gas), “f” is the calculated resonant frequency, and “T” is the measured temperature in degrees Kelvin. 
       FIG. 13  is a schematic diagram of a signal processing technique using a speaker impulse, according to an embodiment of the invention. In this embodiment, driver  1304  applies an impulse to speaker  1305 . The microphone output from microphone  1301  will deliver a resonant response to processor  1303 . The frequency can, in principle, be determined by either time between the edges at the timer/counter, or by processing the analog input stream for spectral content. This embodiment would, in theory, eliminate the reference microphone. In a related embodiment, if the speaker dynamics are well behaved, the reference microphone can, in theory, be eliminated; the phase difference between the microphone&#39;s output and the speaker drive signals can be measured instead. 
       FIG. 14  is a flow chart of the signal processing technique illustrated in  FIG. 13 . At step  1401 , the frequency measurement hardware is configured. This can be performed using either a high-speed timer to measure the time differences between the microphone&#39;s zero crossing, or by using an analog to digital converter using high-frequency sampling and algorithms to examine the spectral content of the output. 
     At step  1402 , an impulse is sent to the speaker. At step  1403 , data is recorded as the microphone&#39;s output reacts to the second-order ringing of the resonator and finishes decaying. The resonant frequency is measured at step  1404  using the microphone&#39;s output. The frequency is associated with the underdamped second-order system. 
     The temperature is then measured at step  1405 , and at step  1406 , the relevant volume is then calculated using the equation (volume=k 1 /((f^2/T)-k 2 ), where k 1  and k 2  are calibration constants (e.g., the physical geometry and molecular properties of the gas), “f” is the calculated resonant frequency, and “T” is the measured temperature in degrees Kelvin. 
     The signal processing techniques described above can be performed using amplitude ratios instead of resonances. This technique does not specifically require the presence of an acoustic port, although with standard electronics, amplitude measurements typically lack the accuracy and precision of phase measurements. With newer, higher performance analog to digital converters and digital signal processors, amplitude ratio measurements can be an accurate substitute. 
       FIG. 15  is an embodiment of the invention that does not require the presence of an acoustic port. Variable volume  1501  can be measured by driving the speaker sinusoidally and measuring the ratio of the amplitudes at microphone  1503  and microphone  1504 . Given that the speaker is a displacement device, the pressure increase in the variable volume will be proportional to the pressure decrease in reference volume  1505 . When reference volume  1505  and variable volume  1501  are equal, both microphones output the same signal level and are 180 degrees out of phase (assuming identical microphones). If the variable volume is one half the size of the reference volume, the output from microphone  1504  is twice that of microphone since, for the same speaker displacement, the acoustic pressure change in variable volume  1501  (as a portion of its nominal value) is twice as large as the change in the reference volume. The relationship is true as long as the drive frequency for the speaker produces an acoustic wavelength much longer than any of the volumes&#39; dimensions. 
     The above amplitude ratio technique is also useful when implementing an acoustic volume sensor with an acoustic port. At frequencies much less than the resonances of the system, the acoustic port becomes effectively transparent (as in  FIG. 16 ), and the “fixed” and “variable” volumes cannot be distinguished. This embodiment can be considered a low-frequency approximation of acoustic volume sensing. 
     At frequencies much higher than the system resonances, the acoustic port&#39;s impedance becomes significant and no acoustic energy passes from the port into the variable volume, as is shown in  FIG. 17 . At such frequencies, the ratio of the amplitudes between microphone  1701  and  1702  is fixed, and is independent of the variable volume (ratio=reference volume/fixed volume). 
       FIG. 18  is a flow chart of a signal processing technique using amplitude ratio measurements, according to an embodiment of the invention. In this embodiment, at step  1801 , the speaker is set into sinusoidal oscillations at a fixed frequency. If an acoustic port is present, the frequency used can be much less than the resonant frequency of the acoustic volume sensor. 
     At step  1802 , the amplitudes output from the two microphones are measured. If desired, the phase of the two outputs can be confirmed to be 180 degrees out of phase. At step  1803 , the variable volume is calculated using the equation volume=reference volume*(reference microphone amplitude/front microphone amplitude). 
     If desired, one can cycle through multiple frequencies to confirm the volume measurement. The measurement should be independent of frequency, the presence of air bubbles within the variable fluid volume, or other “acoustic leaks” or microphone or electronics errors that may be detected. 
     If desired, using an amplitude ratio technique, a volume measurement may be performed using a frequency much larger than the resonant frequency of the system. The volume measurement in this case should be approximately equal to the fixed volume and approximately independent of the variable volume. 
     The foregoing description of the embodiments of the invention has been presented only for the purpose of illustration and description and is not intended to be exhaustive or to limit the invention to the precise forms disclosed. Numerous modifications and adaptations thereof will be apparent to those skilled in the art without departing from the spirit and scope of the present invention.