Abstract:
A treatment system and method for treating a fluid withdrawn and then returned to a living body. The system includes outgoing and incoming fluid lines connected to the living body for transporting the fluid from the living body, through the treatment system, and back to the living body, a device for altering at least the density of the fluid as it flows through the system, and a sensing unit within the system and comprising a device for sensing the density of the fluid as the fluid flows through the sensing unit. The sensing device may be a micromachined Coriolis-based sensor also capable of sensing mass flow rate.

Description:
CROSS REFERENCE TO RELATED APPLICATIONS  
       [0001]     This application claims the benefit of U.S. Provisional Application Ser. No. 60/582,976, filed Jun. 28, 2004. 
     
    
     BACKGROUND OF THE INVENTION  
       [0002]     The present invention generally relates to medical treatment systems that receive and return fluids to a patient. More particularly, this invention relates to a medical treatment system suitable for use in dialysis and other therapies in which a fluid is withdrawn and then returned to a living body, and flow rates, fluid concentrations, temperature, and other process parameters can be accurately sensed with flow rate sensors.  
         [0003]     Hemodialysis and peritoneal dialysis are used to remove impurities from the blood, such as in the treatment of renal failure and various toxic conditions. In hemodialysis, a patient&#39;s blood is shunted from the body through a machine for diffusion and ultrafiltration before being returned to the patient&#39;s circulation system. Peritoneal dialysis requires access to the peritoneal cavity, and involves the use of a catheter to fill the peritoneal cavity with a dialysis solution. Waste products pass from the blood into the dialysis solution through the peritoneum, and are then removed from the peritoneal cavity when the dialysis solution is drained.  
         [0004]     Traditional hemodialysis is performed by accessing the blood stream through an external shunt or arteriovenous fistula. The external shunt is constructed by inserting two cannulas through the skin into a large vein and artery. When performing dialysis the two cannulas are used separately, allowing arterial blood to flow to a dialyzer with which wastes (urea, creatinine, etc.) are removed with a dialysate solution, after which the dialyzed blood is returned to circulation through the cannula in the vein. A blood pump is used to maintain flow through the dialysis system, and various sensors are used to monitor the system, such as to monitor the rate of heparin (anticoagulant) infusion, the conductivity and temperature of the dialysate solution, and blood leak rates in the dialysate solution leaving the dialyzer. Pressure sensors, air bubble detectors, temperature monitors, leak detectors, and conductivity meters have all been used, each usually as a separate individual sensor that often must accommodate the relatively high blood flow rates that must be maintained within the system to avoid clotting. High dialysate flow rates through the dialyzer and the dialysis membrane are also desirable to maximize the removal rate of urea and other wastes. Consequently, accurate flow rate measurement is required, which in the past have included the use of ultrasonic flow sensors, optical sensors, and volumetric containers. Finally, additional sensors, equipment, and procedures have been used to monitor the efficiency and progress of dialysis procedures, such as the slow-flow method, saline-dilution method, blood temperature modules, monitoring urea and hematocrit levels, and the occlusion method.  
         [0005]     It would be desirable to improve yet simplify accurate monitoring of dialysis treatments while avoiding clouting and other dialysis-related problems that can occur include hemorrhaging, hypotension, infection, thrombophlebitis, etc.  
       BRIEF SUMMARY OF THE INVENTION  
       [0006]     The present invention provides a treatment system and method for treating a fluid withdrawn and then returned to a living body. The system includes outgoing and incoming fluid lines connected to the living body for transporting the fluid from the living body, through the treatment system, and back to the living body, means for altering at least the density of the fluid as it flows through the system, and a sensing unit within the system and comprising means for sensing the density of the fluid as the fluid flows through the sensing unit. In preferred embodiments of the invention, the sensing means is also capable of sensing flow rates and temperature. According to the invention, a preferred sensing means comprises a micromachined Coriolis-based mass flow rate and density sensor capable of extreme accuracy.  
         [0007]     A significant advantage of this invention is that various sensors previously required in medical treatment systems used for biological fluids can be replaced by sensing means capable of accurately sensing density. In the context of a dialysis treatment system, density sensors can be used to sense additives (e.g., anticoagulants), wastes (e.g., urea and hematocrit), contaminants (e.g., sterilization fluids), and air bubbles in the blood, sense the concentration of the dialysate used to cleanse the blood, detect blood leakage through the dialyzer, and generally monitor the efficiency and progress of the dialysis procedure. Additional system monitoring capabilities are achieved by including the capability to accurately sense flow rates and temperature, such as ensuring the proper flow rates, dosage rates, mixing, and temperatures of the various fluids, with the result that multiple functions are incorporated into a flow sensor capable of replacing a variety of sensors previously used in dialysis treatment systems, as well as other treatment systems and methods used in the medical field.  
         [0008]     Other objects and advantages of this invention will be better appreciated from the following detailed description. 
     
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0009]      FIG. 1  is a schematic representation of a dialysis treatment system in accordance with an embodiment of this invention.  
         [0010]      FIG. 2  is a perspective view of a sensing unit for use in the treatment system of  FIG. 1 .  
         [0011]      FIGS. 3 and 4  are perspective and cross-sectional views, respectively, of a Coriolis-type mass flow rate sensor suitable for use in the sensing unit of  FIG. 2 . 
     
    
     DETAILED DESCRIPTION OF THE INVENTION  
       [0012]     Illustrated in  FIG. 1  is a dialysis treatment system  10  capable of making use of multiple sensing units  12  of a type or types in accordance with this invention. The system  10  is represented as being generally configured similar to traditional hemodialysis. The blood stream of a patient  14  is accessed through an external shunt or arteriovenous fistula, such as by inserting two cannula  16  and  18  through the skin into a large vein and artery. Arterial blood flows into the system  10  through the cannula  16  and is returned to the patient  14  through the cannula  18  in the vein. The system  10  includes a blood pump  20  connected to a dialyzer  22  with which wastes (urea, creatinine, etc.) are removed from the blood with a dialysate solution. The blood pump  20  is necessary to maintain acceptable flow rate through the system  10  and particularly through the dialyzer  22  to avoid clotting. As is also generally conventional, the system  10  may include an arterial drip chamber  24  and arterial pressure monitor  26  between the pump  20  and dialyzer  22 . An anticoagulant is infused into the blood flowing into the dialyzer  22  with an infusion pump  28 . Before being introduced into the dialyzer  22 , the dialysate solution is prepared by mixing purified water  30  and a dialysate concentrate  32  at a controlled rate. The dialysate solution is drawn from the dialyzer  22  with a pump  34  and monitored with a blood leak detector  36 . Finally, an air bubble detector  38  is shown between the dialyzer  22  and venous cannula  18  to check for air bubbles in the blood that, if delivered to the patient&#39;s blood stream, can cause venous air embolisms that may lead to stroke or death.  
         [0013]     While the invention will be described with reference to the hemodialysis treatment system  10  shown in  FIG. 1 , the invention is also applicable to other treatment systems in which a fluid is withdrawn and then returned to the human body, including but not limited to peritoneal dialysis, hemofiltration and assistance to the kidneys, lungs, liver and artificial organs.  
         [0014]     According to a preferred aspect of the invention, each sensing unit  12  employs a sensor that can accurately measure density, and preferably also flow rate and optionally temperature of a fluid passing through it. More particularly, using the density output of the units  12 , the chemical concentration of any fluid flowing in the system  10  (blood, dialysate, anticoagulant, water, dialysate solution, etc.) can be measured. For example, density output can be used to indicate the urea or hematocrit content within the blood before and after passing through the dialyzer  22  to monitor the effectiveness and progress of a dialysis treatment. Density output can also be utilized to monitor and control the mixing of the water  30  and dialysate concentrate  32  to make the dialysate solution, and to monitor and more accurately control the flow of anticoagulant from the infusion pump  28  into the blood. The sensing units  12  can also be used to detect sterilization fluids like formaldehyde, solvents, and other cleaning solutions and chemicals placed in the system  10  prior to use. If not entirely removed, these cleaning solutions can be potentially injected into the patient  14  causing injury or death. The ability to accurately measure density with the sensing units  12  also enables the detection of air bubbles and estimation of their volume.  
         [0015]     In view of the above, the sensing units  12  of this invention are able to supplement and/or replace many of the sensors previously required by dialysis treatment systems. As replacements for traditional sensing devices in a dialysis treatment system, sensing units  12  of this invention are shown in the individual lines from the water  30  and dialysate concentrate  32  and the line carrying the resulting dialysate solution, thereby taking the place of conductivity and temperature sensors typically used to monitor the dialysate solution before being introduced into the dialyzer  22 . Because of its density-sensing capability, the sensing unit  12  shown in the line connecting the air bubble detector  38  to the venous cannula  18  can replace the bubble detector  38 . As supplemental sensors capable of improving the safety and efficacy of the dialysis treatment, sensing units  12  are shown placed between the arterial cannula  16  and the blood pump  20 , immediately downstream of the drip chamber  24  and in the line downstream of where the anticoagulant enters the blood stream before being introduced into the dialyzer  22 , in the outlet line from the dialyzer  22 , in a discharge line connected to the line between the dialyzer  22  and the bubble detector  38 , and between the bubble detector  38  and the venous cannula  18 . These installations are discussed in more detail below.  
         [0016]     A suitable configuration for a sensing unit  12  for this invention is depicted in  FIG. 2 . The unit  12  is shown as comprising a housing  44  adapted for inline installation, though other configurations are also possible and within the scope of this invention. The housing  44  is formed to have a fluid inlet  46  and outlet  48 , both of which can be adapted for a fluidic connection through such fittings as a Luer, threaded, compression, barbed, lock or other type of fitting. The housing  44  contains a sensor  50  and electronic circuitry  52  located and enclosed within a cavity defined within the housing  44  and closable with a cover (not shown). The sensor  50  is the structure through which the fluid being sensed flows and provides a measurable response to the density and preferably the flow rate of the fluid. The circuitry  52  is preferably configured to communicate with and control the sensor  50  and output information regarding the operation of the sensing unit  12 . The unit  12  further includes an electrical connector  54  by which the circuitry  52  can be coupled to a control unit (not shown) such as a computer or another suitable electronic device capable of controlling and receiving signals from the sensing unit  12 . Such a control unit may be hard-wired to the sensing unit  12  with the connector  54 , or the connector  54  can be replaced with a wireless communication device of a type known in the art, such as an IR, RF, optical, magnetic, etc. Power for the sensor  50  and circuitry  52  can be provided with a battery (not shown) within the housing  44 , delivered through a cable connected via the connector  54 , or delivered telemetrically using known tele-powering techniques.  
         [0017]     The sensor  50  is represented as comprising a tube  56  that serves as a conduit through which the fluid flows as it flows between the inlet  46  and outlet  48  of the housing  44 . In a preferred embodiment of the invention, the sensor  50  and its tube  56  are part of a Coriolis mass flow sensor.  FIGS. 3 and 4  depict a preferred Coriolis mass flow sensor  50  taught in commonly-assigned U.S. Pat. No. 6,477,901 to Tadigadapa et al., whose discussion of the construction and operation of the flow sensor thereof is incorporated herein by reference. In Tadigadapa et al., wafer bonding and silicon etching techniques are used to micromachine the tube  56  and its freestanding portion  58 , which is suspended over a silicon substrate  60 . The freestanding portion  58  of the tube  56  is vibrated at resonance such that, as fluid flows through an internal passage  62  within the tube  56 , the freestanding portion  58  twists under the influence of the Coriolis effect. As explained in Tadigadapa et al., the degree to which the freestanding portion  58  twists (deflects) when vibrated can be correlated to the mass flow rate of the fluid flowing through the tube  56  on the basis of the change in the amplitude of a secondary resonant vibration mode. The density of the fluid is proportional to the natural frequency of the fluid-filled vibrating portion  58 , such that controlling the vibration of the portion  58  to maintain a frequency at or near its resonant frequency will result in the vibration frequency changing if the density of the fluid flowing through the tube  56  changes. As depicted in  FIGS. 2 and 3 , the freestanding portion  58  is preferably U-shaped, though other shapes—both simpler and more complex—are within the scope of this invention.  
         [0018]     As known in the art, micromachining techniques a capable of forming very small elements by bulk etching a substrate (e.g., a silicon wafer), or by surface thin-film etching, the latter of which generally involves depositing a thin film (e.g., polysilicon or metal) on a sacrificial layer (e.g., oxide layer) on a substrate surface and then selectively removing portions of the sacrificial layer to free the deposited thin film. Accordingly, suitable materials for the tube  56  include glass (e.g., quartz and Pyrex), ceramic, metal or a semiconductor, including micromachined silicon, germanium, Si/Ge and GaAs. The substrate  60 , tube  56 , and freestanding portion  58  of the tube  56  are micromachined so that the passage  62  connects ports  64  (one of which is shown) located on the lower surface of the substrate  60 . As previously noted, micromachining technologies are preferably employed to fabricate the tube  56 , enabling the size of the tube  56  and its freestanding portion  58  and passage  62  to be extremely small, such as lengths of about 0.5 mm and cross-sectional areas of about 100 square micrometers, with the result that the sensor  50  is capable of processing very small quantities of fluid.  
         [0019]     The resonant frequency of the freestanding tube portion  58  is determined in part by its mechanical design (shape, size, construction and materials). Suitable frequencies are in the range of 1 kHz to over 100 kHz, depending on the particular fluid being analyzed. Under most circumstances, frequencies above 10 kHz, including ultrasonic frequencies (those in excess of 20 kHz), will be preferred. The amplitude of vibration is preferably adjusted through means used to vibrate the tube portion  58 . For this purpose,  FIG. 3  shows an electrode  66  located beneath the freestanding portion  58  on the surface of the substrate  60 . In the embodiment shown, the tube  56  serves as an electrode (e.g., is formed of doped silicon) that is capacitively coupled to the electrode  66 , enabling the electrode  66  to electrostatically drive the freestanding portion  58 . However, it is foreseeable that the tube  56  could be formed of a nonconductive material, requiring a separate electrode formed on the freestanding portion  58  opposite the electrode  66  for vibrating the freestanding portion  58  electrostatically. Furthermore, the freestanding portion  58  could be driven capacitively, piezoelectrically, piezoresistively, acoustically, ultrasonically, magnetically, optically, or by another actuation technique. Also shown in  FIGS. 3 and 4  are sensing electrodes  68  for providing feedback to enable the vibration frequency and amplitude to be controlled with the circuitry  52  within the sensing unit  12 . While capacitive sensing is preferred, the sensing elements  68  could sense the proximity and motion of the freestanding portion  58  in any other suitable manner.  
         [0020]      FIG. 4  schematically represents the micromachined tube  56  enclosed by a cap  70  bonded or otherwise attached to the substrate  60 . In a preferred embodiment, the bond between the cap  70  and substrate  60  is hermetic, and the resulting enclosure is evacuated to enable the freestanding portion  58  to be driven efficiently at high Q values without damping. A suitable material for the cap  70  is silicon, allowing silicon-to-silicon bonding techniques to be used, though other cap materials and bonding techniques are possible and within the scope of the invention.  
         [0021]     The resonating tube flow sensor  50  of Tadigadapa et al. is preferred for use in the sensing units  12  of this invention, though it is foreseeable that other types of flow sensors could be employed. However, particularly advantageous aspects of the resonating tube sensor of Tadigadapa et al. include its very small size and its ability to precisely measure extremely small amounts of fluids, in contrast to prior art Coriolis-type flow sensors. Furthermore, the preferred flow sensor can attain flow rate measurement accuracies of under +/−1%, in contrast to other types of infusion pumps whose accuracies can range from about +/−15% for volumetric pumps and +/−3% for syringe pumps. While the high cost and the high flow rate requirements for prior art Coriolis-type flow sensors have restricted their use in the drug delivery arena, the flow sensor of Tadigadapa et al. is able to sense the extremely low flow rates (e.g., less than 1 ml/hr) required by infusion therapy applications, and can be used to sense the flow rates associated with the dialysis treatment system  10  of  FIG. 1 . Because of its tube configuration, the sensor  50  also has a bidirectional flow capability that enables the sensing unit  12  to detect incorrect flow direction in the system  10 . The sensing unit  12  can be used in a similar manner with peritoneal dialysis and other forms of patient treatment for renal failure and other renal applications, and for a variety of artificial organs and filtration treatments for the kidneys, lungs and liver. For example, an additional sensing unit  12  is shown in  FIG. 1  as being employed with a urinary catheter  17  to indicate the specific gravity and concentration of the patient&#39;s urine, enabling the patient&#39;s health and renal activity to be closely monitored. In this manner, the output of the sensor  50  can be used to indicate a need for further medical treatment, including dialysis. The sensing unit  12  can be mounted in-line as part of the urinary catheter  17 , or used to analyze samples drawn from the catheter  17 .  
         [0022]     In order to provide the temperature-sensing capability desired for the sensing unit  12 , the sensor  50  is shown in  FIG. 3  as including an on-chip thin film temperature sensor  72 , such as a resistance temperature detector (RTD), in close proximity to the resonating tube  56 . The temperature sensor  72  is shown integrated on to the same substrate  60  as the tube  56  to provide an accurate fluid temperature output, which in addition to providing useful temperature data also enables temperature to be factored into the fluid density measured by the sensor  50 . Alternatively, a temperature sensing capability can be achieved by fabricating a second cantilevered tube on the substrate  60 . According to commonly-assigned U.S. Pat. No. 6,647,778 to Sparks, vibrating the cantilevered tube at resonance enables the tube to measure the temperature of the fluid flowing therethrough on the basis that the Young&#39;s and shear modulus of the materials used to form the tube change with temperature, causing the resonant frequency of the tube to detectably shift with temperature.  
         [0023]     From the above, it can be appreciated that sensing units  12  equipped with the sensor  50  and a temperature-sensing capability (such as with the sensor  72 ) can be advantageously employed in the hemodialysis treatment system  10  of  FIG. 1  to monitor the blood and the various fluids added to and removed from the blood. In particular, it can be seen that the sensing units  12  shown in the individual lines from the water  30  and dialysate concentrate  32  and the line carrying the resulting dialysate solution to the dialyzer  22  are able to accurately monitor and provide feedback control for the flow and subsequent mixing of the water  30  and concentrate  32  before the resultant dialysate solution is introduced into the dialyzer  22 , thereby replacing conductivity and temperature sensors typically used to monitor the dialysate solution.  
         [0024]     The density-sensing capability of the sensing unit  12  shown in the line connecting the air bubble detector  38  to the venous cannula  18  can be used to sense the density and temperature of the blood returning to the patient  14 , the former of which can be used to sense the chemical concentration of urea, hematocrit, blood cells, water, anticoagulants, etc., as well as the presence of other desired and undesired components in the blood. The preferred sensing unit  12  is also sufficiently sensitive to detect fine air bubbles, as reported in commonly-assigned U.S. patent application Ser. No. 10/248,839 to Sparks and U.S. patent application Ser. No. 10/708,509 to Sparks et al. As such, this sensing unit  12  can entirely replace the bubble detector  38  represented in  FIG. 1 .  
         [0025]     The sensing units  12  placed adjacent the arterial and venous cannulas  16  and  18  are shown as being connected to an analyzer  42  capable of comparing the flow rates sensed by these sensing units  12 , enabling the system  10  to detect blood leakage within the system  10  as well as occlusions. As such, these sensing units  12  can replace the blood leak detector  36  represented as being conventionally placed in the outlet line of the dialyzer  22 . Alternatively,  FIG. 1  shows a sensing unit  12  placed in the outline line of the dialyzer  22  to directly sense blood leak rates in the dialysate solution leaving the dialyzer  22  by monitoring the density of the dialysate solution.  
         [0026]     The sensing units  12  placed immediately downstream of the drip chamber  24 , downstream of the anticoagulant fusion pump  28 , and in the line downstream of where the anticoagulant enters the blood stream before entering the dialyzer  22  enables the flow rates of the blood and anticoagulant to be accurately monitored to ensure a proper amount of anticoagulant is present in the blood entering the dialyzer  22 . Dose and dose rates can also be calculated based on the flow rate measured with these sensors. As noted previously, this capability is advantageous because the preferred sensor  50  is capable of greater accuracy than conventional infusion pumps.  
         [0027]     Finally,  FIG. 1  shows a sensing unit  12  placed in a discharge line connected to the line between the dialyzer  22  and the bubble detector  38 . A valve  40  is represented as being placed in the discharge line to allow limited quantities of blood to be drawn from the system  10  and analyzed with the sensing unit  12  for the purpose of measuring the density of the blood, with the capability of sensing waste, sterilization fluids, etc., in the blood before being returned to the patient  14 .  
         [0028]     With the system  10  shown, algorithms relating flow rate, flow direction, fluid density, chemical concentration, and temperature can be developed with each individual sensing unit  12  or inputs from several of these sensing units  12  placed as shown at different points in the dialysis system  10 . These algorithms can be developed to provide better control the treatment that the patient  14  receives than is possible with a single parameter sensor, such as the ultrasonic or optical flow sensors used in the past. The sensing units  12  and their control unit(s) also enable dosage rates of the anticoagulant and dialysate solution to be programmed wirelessly via IR, RF, magnetic, optical, or other communication approach, as can the flow rates and concentrations be monitored to detect malfunctions in the system  10 . With an appropriate control interface, programming can be performed by the physician, care giver, nurse, or pharmacist, such as with a wireless two-way data communication system. In this manner, the dose rate of any additive can be adjusted at any time before or during use and can be recorded for later retrieval and evaluation of the treatment. With the sensing units  12 , safety limits can also be programmed into the system  10  to prevent overdose or warn if occlusions, leaks, or an unsafe urea or drug concentration is detected. The control interface can also receive inputs from other sensors integrated into the system  10  to sense bodily responses, such as glucose, urea, hematocrit, oxygen, respiration rate, pulse, and other chemical or physiological responses to the treatment, and then adjust or halt the medication delivery rate if necessary. Along this approach, the sensing unit  12  shown in  FIG. 1  as monitoring the density (specific gravity) of the patient&#39;s urine can be used to indicate when dialysis is needed and/or control the dialysis treatment, e.g., increase or decrease the flow rate of the dialysate solution, anticoagulant, etc.  
         [0029]     In some of the above applications, the sensing unit  12  and its sensor  50  must accommodate the relatively high blood flow rates maintained within the system  10  to avoid clotting. High dialysate flow rates through the dialyzer  22  and its dialysis membrane are also desirable to maximize the removal rate of urea and other wastes. Such higher flow rates can be accommodated by designing and inserting the sensing unit  12  as a bypass unit, in which a fraction of the fluid is drawn through the sensing unit  12 . Some of the applications within the system  10  also require only density as the sensed parameter. The sensing unit  12  shown in  FIG. 2  and described above can be used for this limited purpose, or other density meters can be used such as meters available from the assignee of the present invention. These sensing units  12  can be used to measure density, specific gravity, or chemical concentration of all the fluid flowing through a line, or used in a by-pass mode to sample a portion of the fluid, or sample small portions of fluid from a line, in which case the sample can be discarded as waste. If the sample does not return to the patient  14 , the sensing unit  12  can be a durable, reusable portion of the dialysis system  10 . Otherwise, the sensing unit  12  can be manufactured as a disposable unit that can be removed after each use of the system  10 . Reusable sensing units  12  can be coupled with a valve to admit small test samples of the fluid of interest, which can then be tested for the presence of sterilization fluid, intentionally added drugs, and/or the chemical concentration of such additives as heparin or another anticoagulant, dialysate concentration, or blood hematocrit/red blood cells. In view of the small size of the preferred sensor  50 , only very small sample volumes are required for analysis, typically on the order of nanoliters to milliliters in volume.  
         [0030]     While the invention has been described in terms of a preferred embodiment, it is apparent that other forms could be adopted by one skilled in the art. Therefore, the scope of the invention is to be limited only by the following claims.