Sensor clip assembly for an optical monitoring system.

The present application is a continuation in part of co-pending North American Patent Application No. 13 / 030,212, filed February 18, 2011, which claims the benefit of North American Provisional Patent Application No. 61 / 414,654, filed on February 17. November 2010, both of which are incorporated in their entirety into the present invention by reference. This patent application also claims the priority of North American Provisional Application No. 61 / 553,078, filed October 28, 2011, and North American Application No. 13 / 034,788, filed February 25, 2011, both of which are incorporated in their entirety by the present invention by reference.

Field of Invention

The present invention relates to optical monitoring systems, and more specifically, to systems for monitoring the presence or concentration of constituents in the blood. The present invention is particularly useful for real-time measurement of hematocrit and / or oxygen saturation levels, when monitoring a patient during hemodialysis or other procedures involving blood flow.

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Background of the Invention

Patients with kidney failure or partial kidney failure usually undergo hemodialysis treatment in order to remove toxins and excess fluids from the blood. To do this, blood is taken from a patient through an entry needle or catheter, which draws blood from a localized artery or vein at a specifically accepted access location - - for example, a surgically placed shunt. on an arm, thigh, subclavian, and the like. The needle or catheter is connected to an extracorporeal tubing that is fed to a peristaltic pump and later to a dialyzer that cleans the blood and removes excess fluid. The clean blood is then returned to the patient through an additional extracorporeal tubing and another needle or catheter. Sometimes a hairpin drip system is located in the hemodialysis circuit to prevent the blood from clotting.

As the drawn blood passes through the dialyzer, it travels through straw-like tubes within the dialyzer, which serve as semi-permeable passageways for unclean blood. Fresh dialysate solution enters the dialyzer at its downdraft end. The dialysate surrounds the straw-like tubes and flows through the dialyzer in the opposite direction of the blood flowing through the tubes. Fresh dialysate

INSTITUTO MEXICANO DS LA rWOTUDAP iXDumui collects toxins that pass through straw-like tubes by diffusion and excess fluids into the blood by ultrafiltration. The dialysate containing the removed toxins and excess fluids are disposed of as waste. The red blood cells remain in the straw-like tubes, and their volume count is not affected by the process.

An optical blood monitoring system is often used during hemodialysis treatment or other treatments that involve extracorporeal blood flow. Another example is the CRIT-LINE® monitoring system sold by Fresenius USA Manufacturing, Inc. of Waltham, MA. The CRIT-LINE® Blood Monitoring System uses optical techniques to non-invasively measure the hematocrit level and oxygen saturation of the blood flowing through the hemodialysis system in real time. The blood monitoring system measures blood in a sterile blood chamber attached in-line to the extracorporeal tubing.

In general, the blood chambers, along with the tubing set and the dialyzer, are replaced for each patient. The blood chamber is designed for single use only. The blood chamber defines an internal blood flow cavity comprising a substantially flat viewing region and two opposing viewing lenses. LED emitters and photodetectors for the optical blood monitor are clamped (for example, by clamping) in place over the blood chamber in the

IMPI® • Mexican wttfuto • EUFROntDA · A- · * iNtxjrntui lenses. Multiple wavelengths can be resolved in light through the blood chamber, and the patient's blood flowing through the chamber with a photodetector that detects the resulting intensity of each wavelength.

Preferred wavelengths for measuring hematocrits are about 810 nm, which is substantially isosbestic for red blood cells, and about 1300 nm, which is substantially isosbestic for water. A ratiometric technique implemented in the CRIT-LINE® controller is substantially as described in US Patent No. 5,372,136, entitled System and Method for Non-lnvasive Hematocrit Monitoring, which was filed on December 13, 1999 and is assigned to the assignee of this application, uses this information on intensity of light to calculate the patient's hematocrit value in real time. The hematocrit value, as widely used in the art, is a percentage determined by the ratio between (1) the volume of red blood cells in a given whole blood sample, and (2) the overall volume of the blood sample. blood.

In a clinical setting, the actual percent change in blood volume that occurs during hemodialysis can be determined in real time from the change in measured hematocrits. Therefore, an optical blood monitor

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It has the ability to non-invasively monitor not only the patient's hematocrit level, but also the real-time change in the patient's blood volume during a hemodialysis treatment session. The ability to monitor real-time change in blood volume helps facilitate safe, effective hemodialysis.

To monitor blood in real time, light-emitting diodes (LEDs), and photodetectors therefor, are mounted on two opposing heads of a sensor holder assembly that fits over the blood chamber. For system accuracy, it is important that the LEDs and photodetectors are located in a predetermined position and orientation each time the sensor holder assembly is clamped in place over the blood chamber. The predetermined position and orientation ensures that the light that travels from the LEDs to the photodetectors travels through the lenses of the blood chamber.

The optical monitor is calibrated for the specific dimensions of the blood chamber, and the specific position and orientation of the sensor holding assembly relative to the blood chamber. For this purpose, the heads of the sensor holders are designed to mate with the blood chamber so that the LEDs and photodetectors are in a known position and orientation. In the CRIT-LINE® monitoring system, the head of the sensor holders

Μ ΙΑ PMHIDAO indwjtmal and the blood chamber have complementary D-shaped configurations.

In conventional systems, optical monitoring is carried out through a separate controller that includes a screen that presents the monitoring data in real time. The controller includes a processor that calculates the displayed data and controls the operation of the LEDs and photodetectors. The controller is conventionally connected to the sensor holder and optical devices by a tether cable. A significant amount of noise is introduced to the analog signal provided by the photodetectors during transmission over a cable to the independent controller, and the amount of energy required to illuminate the LEDs to compensate and ensure a usable analog signal generates heat that degrades the life time of LEDs. Furthermore, the photodiode currents are too small so that any series resistance across its connection is a potential noise source and attenuator. The longer the cable for the analog signal, the more resistance there is to the current and the more noise there will be in the signal.

Brief Description of the Invention

In one embodiment of the present invention, a sensor holder assembly is provided for optically monitoring blood flowing through a blood chamber. Sensor holder assembly includes:

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a housing having two opposite arms capable of being clamped to the blood chamber; at least one emitter at one of the opposite ends; at least one photodetector at the other opposite end positioned relative to at least one emitter, so that the light emitted by the at least one emitter has the ability to be received by at least one photodetector after it passes through the blood chamber to which the sensor holder assembly is attached; a microcontroller within the housing configured to receive conditioned analog signals, wherein the conditioned analog signals are based on raw analog signals generated by the at least one photodetector, to convert the conditioned analog signals into raw digital data, and to calculate at least a parameter corresponding to the blood in a blood chamber to which the sensor holder assembly is attached, based on raw digital data; and an output port configured to transfer from the sensor holder assembly, the results of the calculations carried out by the microcontroller to an external device.

The sensor holder assembly may further include at least one transimpedance amplifier within the housing corresponding to each photodetector for converting raw analog signals to analog voltage signals; and at least one potentiometer that can be controlled

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IMPI XTHTUT · MEXICAN ElARíORlDAB digitally rxwjmuAi ~ inside the housing that corresponds to each photodetector to apply a gain to the analog voltage signals. The microcontroller may be further configured to control the operation of the at least one emitter, and to control the gain applied by the at least one digitally controllable potentiometer, in a way that is synchronized with the operation of the at least one emitter. . At least one of the emitter arm and the photodetector arm may include a cover to block ambient light from being received by the at least one photodetector.

The sensor holder assembly may further include a silicone photodetector and an Indium-Gallium Arsenide photodetector, and the microcontroller may further be configured to calculate a hematocrit value, an oxygen saturation value, and a percent volume change of blood. The output port of the sensor holder assembly may correspond to a USB (Universal Serial Bus) connection, and the external device may be a computer. The output port can be additionally configured to transmit commands received from the external device to the microcontroller. Additionally, the microcontroller may be configured to verify the accuracy of the sensor clip assembly based on a single verification filter, and to recalibrate the sensor clip assembly, when confirming user input of a⁸ IMPI ^

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FROM THE PHOPWDAD ¡NW / mUAL correct verification filter identification code. The microcontroller can also be part of a board that floats within one of the two opposite arms.

In another embodiment, a system is provided for optically monitoring the blood. The system includes: a blood chamber comprising a viewing window and a chamber body; a sensor holder assembly attached to the blood chamber, the sensor holder further including a housing having an emitter arm and a photodetector arm, at least one emitter within the emitter arm, at least one photodetector within the photodetector arm positioned relative to at least one emitter, so that the light emitted by the at least one emitter, has the ability to be received by at least one photodetector after it passes through the blood chamber, a microcontroller within the housing configured to receive conditioned analog signals, wherein the conditioned analog signals are based on raw analog signals generated by the at least one photodetector, to convert the conditioned analog signals into raw digital data, and to calculate at least one parameter corresponding to the blood in a blood chamber to which the sensor holder assembly is clamped based on the raw digital data, and an output port configured to transfer the results of the calculations performed

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The emitter arm and the photodetector arm may further be opposite arms inclined together at opposite first ends of the arms, to form a jaw so that a pressing force applied to the second opposite ends of the arms opens the jaw to allow that the blood chamber is placed between the first opposing ends and remains there when the force is removed. The chamber body of the blood chamber may be tinted in blue, so as to block the reception of ambient light received by the at least one photodetector. The system may further include a verification filter uniquely associated with the sensor holder assembly to determine if recalibration of the sensor holder assembly is required. The output port can be additionally configured to transmit commands received from the external device to the microcontroller; and the microcontroller may be further configured to verify the accuracy of the sensor holder assembly based on the verification filter, and to recalibrate the sensor holder assembly upon confirming user input of a code of identification of

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INSTITUTO MEXICANO ML * n »BME * AD INDUSTRY The correct verification filter. The microcontroller can also be part of a board that floats within the emitter arm and the photodetector arm.

In still another embodiment, an assembly of

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sensor holder having a microcontroller, emitter, and photodetector, with the microcontroller additionally including a processor and a tangible, non-temporary computer-readable medium that has computer-executable instructions to optically monitor blood stored in the same. Computer-executable instructions include: instructions to turn on the emitter, where the emitter corresponds to the photodetector; instructions for synchronizing the conditioning of the raw analog signals generated by the photodetector in a channel corresponding to the photodetector with the operation of the emitter; instructions for calculating at least one parameter corresponding to blood, based on the converted raw digital data from conditioned analog signals, wherein the conditioned analog signals are based on the raw analog signals generated by the photodetector; and instructions for transferring the calculation results to an external device, through an output port.

Computer-executable instructions may also include instructions to control a number of

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ΙΝΠΠυΤΟ MÍXICAN9 DELAniOnitMD INDUrnUAL gain applied by a potentiometer that can be digitally controlled in the channel corresponding to the photodetector, instructions for verifying the accuracy of the sensor holder assembly based on a verification filter uniquely associated with the sensor upon receipt of a corresponding command from the external device, instructions for receiving user input of a verification filter identification code; instructions for recalibrating the sensor holder assembly, if the verification filter identification code entry by the user corresponds to the verification filter uniquely associated with the sensor holder assembly, and / or instructions for transferring the status information that corresponds to the sensor holder assembly to the external device. Computer-executable instructions for transferring calculation results to an external device via an output port may further include instructions for transferring a data stream that includes information pertaining to a hematocrit value, an oxygen saturation value, and a percent change in blood volume.

In yet another embodiment, a sensor holder assembly is provided to optically monitor the blood flowing through the blood chamber. The sensor holder assembly includes: a housing that has two

IMPI tHcrrrvro muucano DEunonuMB iwoumui opposite arms with the ability to be clamped in a blood chamber; means for securing the housing to the blood chamber; at least one emitter at one of the opposite ends; at least one photodetector at the other opposite end positioned relative to at least one emitter, so that the light emitted by the at least one emitter has the ability to be received in at least one photodetector after passing through a blood chamber to which the sensor holder assembly is attached; a signal conditioning circuit configured to apply a gain to, and to filter noise from, the raw analog signals generated by the at least one photodetector; an analog-to-digital converter configured to convert the conditioned analog signals into raw digital data; and an outlet port configured to connect the sensor holder assembly to an external device.

The signal conditioning circuit may further include at least one transimpedance amplifier, at least one digital potentiometer, and a filter circuit. At least one of the two opposite arms may include a cover to block ambient light that is received by at least one photodetector. In a further embodiment, the sensor holder assembly includes a microcontroller within the housing configured to calculate at least one parameter that corresponds to blood in a blood chamber to which

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From the iNBumuAi rwriETY the sensor holder assembly is clamped, based on the raw digital data; and the output port of the sensor holder assembly is further configured to transfer the results of calculations carried out by the microcontroller from the sensor holder assembly to the external device. The output port may be additionally configured to transmit commands received from the external device to the microcontroller, and the microcontroller may be additionally configured to verify the accuracy of the sensor holder assembly based on a uniquely associated verification filter. with the sensor holder assembly upon receipt of a corresponding command from the external device. The microcontroller may be further configured to recalibrate the sensor holder assembly upon confirming a user entry of a correct verification filter identification code. The microcontroller can also be part of a board that floats within one of the two opposite arms.

In yet another embodiment, a system is provided for optically monitoring the blood. The system includes: a blood chamber comprising a viewing window and a chamber body; a sensor holder assembly attached to the blood chamber, a sensor holder assembly housing having an emitter arm and a sensor arm¹⁵ IMPIAS!

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IMBUSnUAL ^^ 3 photodetector, at least one emitter within the emitter arm, at least one photodetector within the photodetector arm positioned relative to at least one emitter, so that the light emitted by the at least one emitter has the capacity If received by at least one photodetector after passing through the blood chamber, a signal conditioning circuit configured to apply a gain to, and to filter noise from, the raw analog signals generated by the at least one photodetector, an analog-to-digital converter configured to convert analog voltage-conditioned signals to raw digital data, and an output port configured to connect the sensor holder assembly to a device external; and the external device, configured to receive data from the sensor holder assembly through the output port.

The signal conditioning circuit may further include at least one transimpedance amplifier, at least one digital potentiometer, and a filter circuit. At least one of the photodetector arm and the emitter arm may include a cover to block ambient light that is received by the at least one photodetector. The chamber body of the blood chamber can be tinted in blue to thereby block ambient light that is received by the at least one photodetector.

In a further embodiment, the sensor holder assembly further includes a microcontroller within the housing configured to calculate at least one parameter corresponding to blood in a blood chamber to which the sensor holder assembly is attached based on the raw digital data, and the output port of the sensor holder assembly is further configured to transfer the results of calculations carried out by the microcontroller from the sensor holder assembly to the external device. The system may further include a verification filter uniquely associated with the sensor holder assembly to determine if recalibration of the sensor holder assembly is required. The output port can be additionally configured to transmit commands received from the external device to the microcontroller, and the microcontroller can be additionally configured to verify the accuracy of the sensor holder assembly based on the verification filter and to recalibrate the sensor holder assembly when confirming user entry of correct verification filter identification code. The microcontroller can be an additional part of a board that floats within the emitter arm and the photodetector arm.

In a further alternative embodiment, the external device is further configured to receive the

ΙΝΤΤΠΤΠΌ MUICANC Μ LAnonSDAA INDUrnUAL raw digital data from the sensor holder assembly through an outlet port, and to calculate at least one parameter that corresponds to the blood in the blood chamber to which the sensor holder assembly is clamped. sensor based on digital data. The external device may be further configured to verify the accuracy of the sensor holder assembly based on a verification filter uniquely associated with the sensor holder assembly, and to recalibrate the sensor holder assembly at the time of confirm the entry by a user of a correct verification filter identification code.

In yet another embodiment, a computing device is provided connected to a sensor holder assembly having an emitter, a photodetector, a signal conditioning circuit, and an analog-to-digital converter. The computing device includes a processor and a tangible, non-temporary computer-readable medium that has computer-executable instructions to optically monitor the blood stored therein. Computer-executable instructions include: instructions to turn on the emitter, where the emitter corresponds to the photodetector; instructions for synchronizing the operation of the signal conditioning circuit with the operation of the emitter corresponding to the photodetector;

¹⁸ IMPI fHrrrrUTU MiXK-ANC M LA INDUSTUAL rlUFUDAD instructions to receive, from the sensor holder assembly, raw digital data converted by the analog-to-digital converter from the conditioned analog signals based on the raw analog signals generated by the photodetector; and instructions for calculating at least one parameter corresponding to blood based on the raw digital data.

Computer-executable instructions may further include instructions to control an amount of gain applied by the signal conditioning circuitry, instructions to verify the accuracy of the sensor holder assembly based on a verification filter uniquely associated with the sensor assembly. sensor clip, instructions for receiving input from a user of a verification filter identification code, and / or instructions for recalibrating the sensor holder assembly, if the user verification filter identification code entry corresponds to the verification filter uniquely associated with the sensor holder assembly. Computer-executable instructions for calculating at least one parameter corresponding to blood based on the raw digital data may further include instructions for calculating a hematocrit value, an oxygen saturation value, and a percentage of change in oxygen. blood volume corresponding to

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Brief Description of Figures

Figure 1 is a block diagram of an example environment illustrating a patient undergoing hemodialysis treatment.

Figure 2 is a perspective view of a blood chamber.

Figure 3 is a perspective view of a sensor holder assembly.

Figure 4 is a perspective view of a sensor holder assembly attached to a blood chamber.

Figure 5 is an internal view of a sensor holder assembly illustrating the internal components of the sensor holder assembly.

Figure 6 is a schematic diagram of a cross section of a sensor holder assembly.

Figure 7 is a flow chart illustrating a process for collecting, processing, and transferring data.

Figure 8 is a block diagram of the components of a sensor holder assembly.

Figure 9 is a functional block diagram of the components of a sensor holder assembly in accordance with the embodiment illustrated in Figure 8.

Figure 10 is a functional block diagram of the components of a sensor holder assembly in accordance with an alternate embodiment.

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Figure 11 is a timing diagram for powering the LEDs in the sensor holder assembly and collecting data from the complementary sensors.

Figure 12 is a screen shot of an example software demo interface on a computer in communication with a sensor clip assembly.

Figures 13A through 13F are screen shots of an example software interface for commercial use on an external computer device in communication with a sensor clip assembly pertaining to verification and recalibration.

Detailed description of the invention

With reference to Figure 1, an example environment suitable for various implementations of the present invention is described. The example environment 100 of Figure 1 schematically represents a system where a patient 10 is undergoing hemodialysis treatment with a sensor holder assembly 34 that monitors the patient's blood in real time as it passes through extracorporeal tubing in the hemodialysis system using a conventional blood chamber and sensor holder assembly. It will be appreciated that the environment described is an example, and that the components of the environment can vary or be modified without departing from the teachings contained in

<img file="MX347286B_D0008.tif" />

this specification.

An inlet needle or catheter 16 is inserted into a patient access site 10, such as a shunt in the arm, and connected to extracorporeal tubing 18 leading to a peristaltic pump 20, part of a hemodialysis machine 12, and subsequently to a dialyzer or blood filter 22. Dialyzer 22 removes toxins and excess fluid from the patient's blood. Dialyzed blood returns from dialyzer 22 to the patient through extracorporeal tubing 24, and a return needle or catheter 26. Extracorporeal blood flow in the United States of America generally receives a hairpin drip system to prevent clotting , although this is not shown in figure 1. Excess fluids and toxins are flushed through clean dialysate fluid, which is supplied to dialyzer 22 through tube 28, and disposed of for waste through tube 30. A typical hemodialysis treatment session in the United States States of America, it takes approximately 3 to 5 hours. In a typical hemodialysis treatment as described in Figure 1, the access site draws arterial blood from the patient. If arterial access is not available, then a venous catheter can be used to access the patient's blood. As mentioned, other dialysis applications, such as low flow Continuous Renal Replacement Therapy (CRRT) sometimes used in the Nursing Unit

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Intensive, or applications such as high-level flow perfusion measurements during cardiac surgery, also measure the patient's blood. Applications include closed-loop blood flow devices, such as conventional dialysis machines, but may also include applications with cyclic blood cleansing devices, such as the single-needle dialysis technique. The current technique indicates that the oxygen saturation levels in the venous blood correlate with the cardiac output of the patient.

Optical blood monitoring is performed through sensor holder assembly 34, which is attached to a blood chamber 32. Although clamping is described in the present invention with respect to clamping via a spring-canted bridge, it will be appreciated that the sensor holder assembly is not required to be a clamp, and can be clamped in a variety of ways, such as such as through the use of a plug connector, a snap connector, different types of hinges, and other types of fastening mechanisms known to those skilled in the art. The digital data, which may be raw digital data (that is, it represents readings from the photodetectors of the sensor holder assembly that have been conditioned and converted to digital form) or processed digital data (that is, it represents calculations based on

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sensor clip assembly photodetector readings), is output from sensor clip assembly 34 through a suitable digital processing port, such as a USB port. Blood chamber 32 is preferably located in line with extracorporeal tubing 18 in the upstream of dialyzer 22, although it can be located anywhere in the blood line. Blood from peristaltic pump 20 flows through tubing 18 into blood chamber 32. In one embodiment, sensor holder assembly 34 includes LED photoemitters that emit light at substantially 810 nm, which is isosbestic for blood cells. red, substantially 1300 nm, which is isosbestic for water, and substantially 660 nm, which is sensitive for oxygenated hemoglobin. The blood chamber 32 includes windows so that the emitters and detectors of the sensor can observe the blood flowing through the blood chamber 32, and determine the real-time hematocrit value and oxygen saturation value of the patient. using known ratiometric techniques. It will be appreciated that other types of emitters can be used in addition to LED emitters, such as laser diodes or a white light source in combination with a prism.

Figures 2-4 show blood chamber 32 and sensor holder assembly 34 in a specific embodiment. Referring to Figure 2, the body 301 of

INSTITUTO MUICANL 'M LA NtoriUMC INDUSTRIAL * * Blood Chamber 32 is made of polycarbonate tinted in blue, medical grade, molded or other suitable material. The viewing window 306 in the camera body 301 is preferably made of a clear medical grade polycarbonate material that is molded with a polished finish to facilitate reliable light transmission, for example, Bayer Makrolon FCR2458-551 15 (no regrinding allowed), which is an approved blood contact, USP XX11, Class V1. The material is expected to be certified for a grade number, batch number, and date of manufacture.

Although only one side of blood chamber 32 is illustrated in Figure 2, both sides of blood chamber 32 include lenses 305 having viewing windows. As can be seen in Figure 2, each of the lenses 305 includes two rings of concentric ridges, and the inner ring surrounds the viewing window 306 of the lens 305. The outer ring is at the periphery of the lens 305, where the lens matches the 301 camera body. The annular surface area of ​​lens 305 between the inner and outer rings defines a recess to receive the cover of the sensor holder assembly. When engaged, the recess and spring camber of the sensor holder assembly hold the sensor holder assembly 34 and blood chamber 32 together, as described in greater detail below. To prevent relative rotation of the clip and the blood chamber, a finger 307 extends radially inward from the crest of the outer ring. This finger 307 engages a notch in the cover, and serves to rotatably secure the attached fastener assembly and blood chamber. The inlet and outlet of the blood chamber 32 are designed to be compatible with standard connection devices in the medical industry, conventionally known as luer lock connectors. Alternatively, one or both of the inlet and outlet may be configured to include an opening that accepts the outer circumference of the corresponding pipe. Additional details regarding the configuration and design of blood chamber 32 can be found in North American Provisional Application No. 61 / 553,078, North American Application No. 13 / 034,788, and North American Application No. 12 / 876,572.

Figure 3 illustrates an external view of sensor holder assembly 34, and Figure 4 provides an example of sensor holder assembly 34 clamped in blood chamber 32. Sensor holder assembly 34 monitors flow of patient's blood through blood chamber 32 (e.g., hematocrit level, hemoglobin, change in blood volume and oxygen saturation, and / or other constituents of blood flowing through blood chamber 32). The Sensor Holder Assembly Case 34

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includes a 344 LED emitter arm and a photodetector arm

346, which are connected via a spring-canted bridge 348. The LED emitter arm 344 contains an emitter sub-assembly with at least two LED emitters, one emitting infrared light radiation in the first wavelength (Λ0 of approximately 1300 nm, and another that emits infrared light radiation at a second wavelength (λ₂) of about 810 nm. The LED emitter also preferably includes a third LED emitter for emitting visible light radiation at a third wavelength (λ₃) of about 660 nm. Other wavelengths can be substituted or added to measure additional blood constituents or the properties of other fluids. The detector arm 346 preferably contains two types of photodetectors: a silicone photodetector to detect the approximate wavelengths of 660 nm and 810 nm, and an indium-gallium-arsenide photodetector, to detect a wavelength of approximately 1300 nm. .

Sensor holder assembly 34 further includes two covers. A cover 340 is on the inner housing part of the emitter arm subassembly 344, and prevents ambient light from entering the blood chamber through the viewing windows. A second cover 342 is on the inner housing part of the detector arm subassembly 346, and also prevents ambient light from entering the chamber.

<img file="MX347286B_D0011.tif" />

blood through the viewing windows. The cover 342 contains an external annular edge or a passage surface 350 and an internal annular edge or passage surface 352. The difference in the heights of the passage surfaces 350, 352, correspond to the height of an annular wall in one part. exterior of blood chamber 32 (see figure 2), and also at the height at which the surface of the window rises above a submerged reservoir on one side of blood chamber 32. Preferably, the shape and surface area of ​​the outer annular passage surface 350 substantially complements the shape and surface area of ​​the mating surfaces of the respective covers in the blood chamber 32, in order to maximize blockage of ambient light. Cover 340 is configured in a similar way to mate with the opposite outer wall of blood chamber 32. Additional details regarding the structure and design of the sensor holder assembly case 34 can be found in North American Provisional Application No. 61 / 553,078, North American Application No. 13 / 034,788, and North American Application No. 12 / 876,572.

Figure 5 illustrates an internal view of the sensor holder assembly 34. In Figure 5, the emitter arm casing 344 and the detector arm 346 are shown transparently through the dotted lines. Emitter arm 344 includes an LED circuit board 148 and a board

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INSTITUTO MEXICANO Λ5ί · | μ ιλ rnoeisDAr INDUSTRIAL of transmitter and processor circuit 150. The detector arm 346 of the sensor holder assembly 34 includes a detector circuit board 152, a receiver and communications board 154, and a power supply circuit board 156. A serial cable (eg, S-232, USB, etc.) 158 is connected to the receiver and communications circuit board 154, and the power supply board 156 found in the detector arm. Receiver and communications board 154 is connected to transmitter and processor board 150, for example, through a pair of seven conduit ribbon cables 160. It will be appreciated that other types of serial cables may also be used, such as a cable having a NEMA 250 rated bayonet lock connector. It will be appreciated that the particular configuration of the boards and connectors illustrated in figure 5 is merely an example.For example, all the boards can be mounted on one arm or the other (except for the emitters and detectors, which must be mounted on the opposite arms), or as in another embodiment described below, wherein the sensor holder assembly 34 includes limited circuitry for processing the analog signals to raw digital data, for transmission via a cable, to an external computer device.

Figure 6 illustrates a schematic diagram of a cross section of the sensor holder assembly 34

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IMBUSnUAl attached to a blood chamber 32. The housing for the sensor holder assembly 34 includes an internal housing structure 162, as well as external housing shells 164, 166 for the emitter arm 144, and the detector arm 146, respectively. Internal housing structure 162 serves as the internal housing for both emitter arm 144 and detector arm 146. The bridge 102 spans between the positions of the internal frame housing that correspond to the emitter arm 144 and the detector arm 146. The bridge 102 includes an internal channel through which a pair of ribbon cables 160 passes. The housing structure Internal 162 also includes a spring that encompasses both arms 144, 146 and bridge 102 (spring not shown). The spring biases the distal ends of emitter arm 144 and detector arm 146 toward each other so that they hold securely in blood chamber 32. The outer shell 164 of emitter arm 144 includes struts 170 that secure the LED circuit board 148 in the proper position on the emitter arm 144. Similarly, the outer shell 166 of the detector arm 146 includes struts 172 that secure the detector circuit board 152 in the proper position.

Transmitter and processor circuit board 150 is contained within a compartment 174 in emitter arm 144 defined by internal housing structure 162

<img file="MX347286B_D0013.tif" />

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DELA «OREDAD INDUmiAI and the emitter arm shell 164. The receiver and communications circuit board 154 and the power supply board 156 are located in a compartment 176 defined by the internal housing structure 162 and the arm shell. detector 166. In order to avoid vibration damage to boards 150, 154, and 156 (for example, due to sonic welding of housing components), it has been found desirable that board 150 in compartment 174 and boards 154 and 156 in compartment 176, are not mounted directly to the outer shell or housing frame. Power supply board 156 is physically mounted on receiver and communications circuit board 154. One end of the receiver and communications circuit board 154 is supported by the flexible ribbon cables 160, and the other end is supported by the release of molded rubber deformation of the serial cable (eg, USB) 158. The board receiver and communications 154 is also connected via jumper 184 to detector board 152. This mounting arrangement allows boards 154 and 156 to float in housing compartment 176 and isolate boards from potentially damaging vibrations. The components on the detector board 152, as well as the LED board 148, are encapsulated within epoxy to secure the components of the boards 152, 148, and protect the components from damage or vibration due to vibration. Transmitter and processor circuit board 150 is supported by flexible ribbon cable 160 and also bridge 180. Similarly, this mounting arrangement allows board 150 to float in housing compartment 174 on emitter arm 144 and isolate board 150 from potentially harmful vibrations.

It will be appreciated that the covers illustrated above in Figures 3 to 6 are most convenient in extreme situations, such as when a patient has very low oxygen levels in the venous blood. Therefore, although Figures 3-6 illustrate covers for blocking ambient light, an alternative embodiment of the sensor holder assembly 34 illustrated in Figures 3-6 may not include the covers for blocking ambient light as shown. described above. Furthermore, it will be appreciated that the embodiment of the sensor holder assembly 34 illustrated in Figures 3-6 is merely exemplary and that one skilled in the art may have the ability to modify the configuration of various components without departing from the principles. of the invention described herein.

Turning now to Figure 7, a general process for initiating and conducting blood monitoring is illustrated. In step 701, a user first turns on the monitoring system, and, in step 703, the system is started, the calibration parameters are loaded, the calibration registers are set.

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Of LA ΠΙΟΠΙΙΜ · Ota industrial control, and the system timers are started. Calibration parameters are initially determined after a sensor holder assembly is manufactured, and can be updated in the field when appropriate.

Factory calibrations are initially completed by measuring absorption filters built within a blood chamber (factory calibration filters). These factory calibration filters are constructed of stable, light-path materials, and are constructed to provide benchmarks in absorption that correlate with actual transmission rates found in blood. Although a simple factory calibration filter can be used, the preferred method is to use at least two factory calibration filters with different transmit light values ​​per wavelength, so that slopes can be set for each wavelength ( gains) and calibration intercepts (offsets). These slopes and intercepts are stored in non-volatile memory (either in the sensor holder assembly 34 or in the external computing device) and are used in measurements to ensure that signals are accurately interpreted in blood values. . It is common to verify that calibrations are accurate by circulating human blood in a closed circuit, and to measure the blood against a known measuring device such as a meter.³³ IMPI

INSTITUTO MEXICANO MLAMñflUMD INDUTHUA1 cell. This is done at different levels of hematocrit and oxygen, to validate the calibration of the sensor holder assembly 34.

After the sensor holder assembly 34 is calibrated, a unique verification filter is assigned that can be attached to the data cable or to an external computer device that interfaces with the sensor holder assembly. It is common practice that at least monthly, the user places the sensor clip on the single matched verification filter and verifies that the sensor clip assembly 34 reads the same values ​​from the filter as when calibrated. If the values ​​are within the original measurement limits plus or minus a prescribed offset, then the sensor holder assembly 34 passes the verification test and is allowed to continue to function. If the measurements on the filter are out of limits, then the device is taken out of service.

After a simple verification failure, the user should clean the surfaces of the sensor holder assembly 34 and ensure that the sensor holder assembly 34 is properly seated in the verification filter. Verification is attempted a second time. If the device fails again, the user is presented with the option to calibrate in the field. With sensor holder assembly 34 in place

<img file="MX347286B_D0014.tif" />

in the verification filter, an algorithm maps the value

IMPI

INTHTUTO MMICAN · KLAFMmaAT INDUSTRIAL current measurement, with the value of when the device was calibrated. New correction values ​​are calculated and implemented in the software. If the sensor holder assembly 34 is too far outside the established limits for reliable field calibration, the device remains disabled and must be replaced. If the device is recalibrated successfully, an additional verification test is performed. Passing the verification test puts the unit back into service.

After the system is ready, and a patient has begun hemodialysis treatment, raw analog data is collected through the sensor holder assembly in step 707. The signals received are in response to illumination of the blood. through the LEDs energized in sequence. This raw analog data includes raw analog current signals received at photodetectors based on oxygen, hematocrit, and water-sensitive LED frequencies, as well as temperature readings. These raw analog current signals are converted to the voltage domain by transimpedance amplifiers, processed by a signal conditioning circuit, and subsequently digitized through an A-to-D converter.

In step 709, sensor holder assembly 34 calculates hematocrits, oxygen saturation, and change

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Μπττυτο mukaho • c the INDUTTMAL name in blood volume associated with the passage of blood through the blood chamber 32, to which the sensor holder assembly 34 adheres based on the raw data and the parameters of calibration, using a ratiometric model, substantially as described in US Patent No. 5,372,136 entitled System and Method for Non-lnvasive Hematocrit Monitoring, filed December 13, 1999, and assigned to the assignee of the present application, which is incorporated in its entirety into the present invention as reference. The intensity of the light received at each of the various wavelengths is reduced by attenuation and dispersion of the fixed intensity of the visible and infrared light emitted from each of the LED emitters. Beer's Law, for each wavelength of light, describes attenuation and scattering as follows:

°^w Eq. (1) where i_n = the intensity of light received at wavelength n after attenuation and scattering; the intensity of transmitted light at incident wavelength n for the measured medium; e = the natural exponential term; ε = the extinction coefficient for the measured medium (p - blood chamber polycarbonate, b - blood); X = the molar concentration of the measured medium (p - blood chamber polycarbonate, b blood); and d = the distance through the measured medium (pt blood chamber polycarbonate transmission, b blood, pr - blood chamber polycarbonate reception).

Since the properties of the polycarbonate blood chamber do not change, the first and third exponential terms in Equation (1) above are constant for each wavelength. Subsequently, mathematically these constant terms are multiplicative with the initial constant term lo-n, which represents the fixed intensity of the transmitted radiation of the respective LED emitter. For simplification purposes, Equation (1) can be rewritten as follows using the extinction coefficients by volume and a modified initial constant Γ₀._η as follows:

no N

Ec- (2) where i_n = the intensity of light received at wavelength n after attenuation and scattering since the detector was still at the reception blood limit; a = the volume extinction coefficient (a_b = c_b X_b) and l'on = the equivalent transmitted light intensity at wavelength n, as if applied to the transmission blood limit encompassing losses through the blood chamber. It should be noted that the term l '₀._n is the incident light intensity at ^J IMPI ^ mrrmjTO mukano otíAnoruoA »

INBUSTlUt the blood with the blood chamber leaks included.

Using the method defined in Equation (2) above, the 810 nm wavelength which is isosbestic for red blood cells and the 1300 nm wavelength which is isosbestic for water can be used to determine the hematocrit of the patient. The ratio of the normalized amplitudes of the intensity measured at these two wavelengths yields the ratio of the compound extinction values ​​α for the red blood cells and the water constituents in the blood chamber, respectively. Subsequently, a mathematical function defines the measured HCT value:

<td></td><td></td><td>&lt;7 M</td><td></td>

<td></td><td>In</td><td>^F 810 ,</td><td></td>

<td>HCT = f</td><td></td><td>I-810) / \</td><td></td>

<td></td><td>In</td><td> /1300</td><td>Eq. (3) /</td>

<td></td><td></td><td> &lt;*0-1300 ) _</td><td></td>

where /₈₁₀ is the light intensity of the photoreceptor at 810 nm, / '1300 is the infrared intensity of the photodetector at 1300 nm, and lo-βίο and I0-1300 are constants representing the incident intensity in the blood that encompasses losses through the blood chamber. The above equation holds true, assuming that the flow of blood through the blood chamber 32 is in a constant state, that is, constant pressure and constant flow range.

The preferred function f [] is a second-order polynomial that has the following form:

HCT =

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MUICANO INSTITUTE mlapnoruiad INOUrnUAL

<img file="MX347286B_D0015.tif" />

<img file="MX347286B_D0016.tif" />

(i Ί

In &lt;^ 0-810 and í i Ί &lt;Λ-1300,

Eq. (4)

A second order polynomial is normally adequate as long as the incident of infrared radiation at the first and second wavelengths is substantially isosbestic.

The oxygen saturation level, or the level of oxygenated hemoglobin, is determined with the ratiometric model that has the following form:

<td></td><td></td><td rowspan="2">(i '660</td><td></td>

<td></td><td>In</td><td></td>

<td>SAT - g</td><td>In</td><td rowspan="2">V0-660 J (&gt; ^ 810 U- «J</td><td></td>

<td></td><td></td><td> —</td>

Eq. (5) where /₆6th is the light intensity of the photoreceptor at 660 nm, / βίο is the intensity of the photodetector at 810 nm and l_OR-66o and lo8io are constants representing the incident intensity in the blood that encompasses losses through the blood chamber. The function g [], is a mathematical function determined based on the experimental data to transfer the level of oxygen saturation, again preferably in a second order polynomial. It may be useful to use a second order polynomial pair depending on the hematocrit value, or a separate 810 nm calibration for oxygen and hematocrit. Similar to the case for the calculation for

<img file="MX347286B_D0017.tif" />

hematocrits, errors in the SAT oxygen saturation value can occur, if there are errors in the measured intensity of light at either the 660 nm or 810 nm wavelengths.

After these calculations are carried out, in step 711, the resulting data is transferred by the sensor holder assembly through a serial port (for example, such as a USB connector) to a device with the capacity to display the data (for example, a computer with a monitor). These steps of collecting raw data, calculating hematocrit, oxygen saturation, and blood volume change, and transferring data through the serial port, continue to take place (i.e., the process returns to node A in step 705) until the system is shut down in step 713. It will be appreciated that these steps can occur simultaneously (for example, although certain raw data is being used in the calculations or processed data is being transferred through the serial port, other raw data is being collected at the same time).

As mentioned above, the collection of the raw data, the calculation of hematocrit, oxygen saturation, and blood volume change, and the transfer of data through a serial port, all are carried out through of the components of the sensor holder assembly 34. By providing this functionality in the

IMPI

INSTITUTO MURAN »DC LA FMFUBAD INDUSTRIAL sensor holder 34, it is conveniently allowed for the analog signal data from the photodetectors to be collected, and converted into digital signals without significant transmission loss, which in turn reduces the amount of noise present in the output data that is finally displayed. In addition, converting data to digital, from within the sensor holder assembly 34, reduces the transmission distance of the analog signals, which reduces the amount of noise introduced by the analog transmission, and allows signal ratios to be achieved. to adequate noise at lower transmit power. Therefore, the system has the ability to drive the LED emitters with lower electrical currents, which decreases heat generation and extends the life of the LEDs, as well as the time needed between calibrations.

Turning now to Figure 8, the general process of Figure 7 will be described in greater detail with respect to the components of a sensor holder assembly 34. Figure 8 illustrates the communication of electrical signals within the context of the sensor assembly. sensor holder 34 (see Figures 5 and 6). There are a plurality of electrical connections 180 between the transmitter and processor circuit board 150 and the LED circuit board 148. The processor and transmitter circuit board 150 includes a microcontroller 182, which among other tasks, controls the

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ΙΝΓΓΠυΤΟ MUICANC OF THE INDUITIUAL MOftEDAB

<img file="MX347286B_D0018.tif" />

input current to the LED emitters on the LED board 148 via the leads 180. As mentioned, the LED circuit board 148 preferably includes an LED that emits red light at about 660 nm, an LED that emits infrared light at about 810 nm. nm, and another LED that emits infrared light at about 1300 nm. Microcontroller 182 preferably includes a built-in AD converter. The microcontroller 182 controls the current output to the LEDs, preferably so that each of the LEDs produces a known calibrated intensity at the respective wavelength. As mentioned above, the microcontroller 182 must be initially calibrated, and recalibrated as necessary to account for differences in the output efficiency of the LEDs for each clamp assembly. Alternatively, in a further embodiment, because the sensor holder assembly is relatively inexpensive to manufacture, the sensor holder assembly is simply replaced once the clamp assembly is out of calibration.

Dotted line 178 illustrates visible and / or infrared light being transmitted from an LED on LED circuit board 148, to one of the photodetectors on detector circuit board 152. Detector board 152 includes at least a Silicon photodetector and at least one indium gallium-arsenide photodetector. Microcontroller 182 implements a routine

<img file="MX347286B_D0019.tif" />

multiplexing so that the LED emission is active and correlates with its respective received signal through the photodiodes for visible and infrared light. An example of multiplexing is time-based switching of each LED, and coupling the detector to successive unique time periods resulting in unique time period measurements for each wavelength. This time-based method is called switching. A plurality of conductors connect detector board 152 to receiver and communications circuit board 154. Conductors 184 include paths to ground, as well as electrical connections to the anode and cathode of the Silicon diode photodetector (s), and an electrical connection. to the anode and cathode of the indium-g alio-a rsenide diode photodetector (s).

Photodetector signals are typically relatively weak (in the μ range) with a poor signal-to-noise ratio. The receiver and communications board 154 includes transimpedance amplifiers 186 that convert analog current signals (µΑ) from silicone and indium-gallium-arsenide photodetectors to analog voltage signals (mV). Analog voltage signals from transimpedance amplifier 186 are transmitted to digital potentiometers 188. Leads 194 transmit timing signals from microcontroller 182 to control timing of potentiometers 188, with the

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<img file="MX347286B_D0020.tif" />

fWHTUTO MEXICANO DELA PROFIXDAD industrial object to ensure that a correct commutation occurs based on time. Time-switched voltage signals from potentiometers 188 are transmitted to a summation junction. The time-switched voltage signal made up of the summation junction is subsequently processed through signal filtering hardware 190 to loosen the noise from the analog voltage signal. The clean analog signal is subsequently separated by microcontroller 182 via line 192 to the built-in AD converter, where each signal is measured separately. These de-switched signals represent the intensity of visible and infrared light at the respective wavelength 660 nm, 810 nm, or 1300 nm as appropriate, depending on the time spent in the de-switching process.

Microcontroller 182 is a program with the ratiometric pattern, calibrated (substantially as described in the aforementioned US Patent No. 5,372,136) to calculate patient hematocrits. It is also preferably programmed with a ratiometric model, calibrated to calculate the patient's oxygen saturation level. The HCT and SAT values ​​are based on the signals detected from the silicon and indiumgalium-a rsenide detectors that are filtered, de-switched and calculated through the microcontroller 182. The ratiometric model to calculate the HCT is of the form of Equation (3 ) referred to above, and preferably is a polynomial of second

IMPI iwhtuto Mexicano mea nom »AD industrial.

<img file="MX347286B_D0021.tif" />

order that has a form as described above in Equation (4). The ratiometric model for determining the oxygen saturation level (SAT) is in the form of Equation (5) above, and preferably it is also in the form of a second order polynomial.

The calculated values ​​for HCT and SAT are transferred as digital signals through microcontroller 182 via conductor 196, and transmitted to a serial communications chip 198 on the receiver and communications board 154. The serial communications chip converts the digital signals from microcontroller 182, into data signals that are transmitted over lines 200 to serial cable 158. It is preferred to transmit the data signals via a USB cable using a conventional USB protocol.

The data transmitted over the serial cable (e.g., USB) 158, preferably includes system status information, as well as real-time HCT and SAT information, and also preferably hemoglobin and change in volume information. blood that can be calculated from the HCT information. Other data computed by microcontroller 182 can also be transmitted over serial cable 158 in a similar manner. Desirably, a USB cable transmits the data to another piece of equipment, such as a personal computer on ⁰ IMPI ^ ΐΜΓΠτυτυ Mexican

I HEARD THE FMMUMD

INDUSTRIAL network or standalone, which can accept cable receptacle

USB and data as known in the art. The following is an example format for an output data stream with a corresponding table, Table 1:

&lt;STX&gt; D c hh.h oo.o ssssssss xxxx &lt;CR&gt; &lt;LF&gt;

Table I: Example Output Data Stream

<td>Character / Field</td><td>Description</td>

<td>&lt;STX&gt;</td><td>0x02, Start of text control character</td>

<td>D</td><td>ASCII D</td>

<td>C</td><td>ASCII integer representation of the counter</td>

<td>hh.h</td><td>ASCII decimal representation of Hematocrit</td>

<td> 00.0</td><td>ASCII decimal representation of Oxygen Saturation</td>

<td>Ssssssss</td><td>ASCII hex representation of 32-bit status bits</td>

<td>Xxxx</td><td>Hex ASCII representation of the 16-bit CRC. The CRC generation includes the data that begins with the first character after leading the &lt;STX&gt; character up to and including the space character that precedes the CRC value. The CRC calculation does not include the characters &lt;STX&gt;, the CRC, or &lt;CR&gt; &lt;LF&gt;.</td>

<td>&lt;CR&gt;</td><td>OxOD, Carriage Return Character</td>

<td>&lt;LF&gt;</td><td>OxOA, Line Feed Character</td>

Although not illustrated in Table I, it will be appreciated that an error detection protocol, such as a checksum, may be included in the output data stream.

Instructions for the sensor holder assembly 34 from connected equipment (for example, a computer) can be transmitted through the USB cable 158, through the USB communications chip 198 on the receiver board, and

Μτπυτο MEXICAN DELA MUWWMD mousnuiu.

communications 154, and through lead 202 to also control microcontroller 182. Table II below provides a set of example commands and corresponding descriptions that can be used:

IMPI tx JTTTUT · MfcXKAN

M la moni ** INDUSTRIAL

<img file="MX347286B_D0022.tif" />

Table II: Example User Command Set

<td>Command</td><td>Description</td>

<td>to</td><td>Check accuracy</td>

<td>F</td><td>Carry out field calibration</td>

<td> 0</td><td>Set transfer mode label. The transfer mode label allows the operator to custom design the transfer data in normal mode. Regardless of the label settings, Hct, Sat, and Status will always carry over. &lt;or NN&gt; where the range NN "OO" - "FF". The bits are defined as follows: Bit 0 = Includes unit ID Bit 1 = 0 = Counter extension @ 10, 1 = Continuous counter Bit 2 = Includes raw Hct value Bit 3 = Includes LED voltages Bit 4 = Includes Reference Temperature and Voltages Bit 5 = Includes 800% T (Hct value) Bit 6 = Includes% T values ​​(Bit 5 invalid) Bit 7 = Disable input “echo”</td>

<td>r</td><td>Reboot the system</td>

<td>rv</td><td>Generate CLM “rvt” style transfer</td>

<td>s</td><td>Set sample range, &lt;s n&gt; where: n = “1” (One sample per second) by Omission n = "2" (Two samples per second) n = "A" (Ten samples per second) η = "B" (One sample every two seconds)</td>

<td>t</td><td>Enable / disable data transfer &lt;t 1&gt; enable, &lt;t 0&gt; disable, &lt;t&gt; toggle</td>

<td>or</td><td>Get unit id</td>

<td>X</td><td>Disconnect LEDs</td>

<td>Y</td><td>Connect LEDs</td>

<td>z</td><td>Set the LED sleep mode. Set LEDs to Sleep Mode Cancellation</td>

<img file="MX347286B_D0023.tif" />

Although not illustrated in Table II, it will be appreciated that an error detection protocol such as a checksum can be included with the user commands.

The USB cable 158 provides 5V USB power to the power supply board 156. The power supply board 156 conditions the power from the USB port, and isolates the electrical components in the sensor holder assembly 34 from direct connection. to USB power, which may not be gentle enough for reliable operation of the sensor holder assembly. The 156 power supply board quietly and accurately regenerates the 5V and 3.3V power to facilitate the reliable operation of the LED emitter and detector pairs, as well as the other electronic components in the power clamp assembly. sensor 34. Power supply board 156 uses switching regulators to convert between 5V and 3.3V powered signals as needed. Switching regulators have been found to be very efficient, and do not generate a significant heat load.

Figure 9 provides a functional block diagram of the sensor holder assembly 34 described above with respect to Figure 8. Microcontroller 182 generates timing signals 903, 905 for both the transmitting and receiving sections of the sensor holder assembly. sensor 34. In turn, the transmitter tunes each wavelength οαπτυτο muucang DELA nOMUMD INDWSTtlAL ~ * - = of light, to illuminate the blood under test, and the resulting amplitude of each signal is measured through a corresponding detector diode. Subsequently the measured amplitudes are used to calculate the blood parameters. This signaling method is called time-domain multiplexing. Although time domain multiplexing in an exemplary embodiment is explained in greater detail in the present invention, it will be appreciated that other multiplexing methods are possible. It will be further appreciated that the microcontroller 182 includes a tangible, non-temporary computer-readable medium (such as flash memory RAM, EEPROM, etc.) and that the operations performed by the microcontroller are in accordance with a processor that executes computer-executable instructions stored on the computer-readable medium.

In this example, the LED emitter is first manipulated with an oxygen sensitive wavelength 941. In the receiver part, the Silicon 911 photodetector is used during this time interval. A gain of the InGaAs channel digitally controlled potentiometer resistor 188 is set to zero, and the appropriate gain is adjusted with a silicone channel digitally controlled potentiometer resistor. The signal is then filtered to eliminate noise and feed a detector circuit that generates a Direct Current (DC) voltage level high enough to

IMPI ΐΝΓΠτυτο Mexican DE LA nmou) INDUSTRIAL

<img file="MX347286B_D0024.tif" />

measured by Analog-to-Digital Converter (ADC) 931 on microcontroller 182 (measure filter circuit and detector circuit illustrated as a single block 921). The resolution of the signal can be controlled by software feedback to the digital potentiometer resistor, so that if too few bits are activated in the CAD, the signal can be increased in level for the next measurement. Because the receiver part is synchronized with the transmitter signal through the microcontroller 182 by synchronization signals 903, 905, measurements are made only when the transmitters are active. This conveniently reduces the processing load on the microcontroller 182.

After a first measurement is completed, the oxygen sensitive wavelength LED emitter 941 turns off for a period of time called the "guard band." This time allows the receiving circuit to settle back to the no-signal state and prevents the residual signal from overlapping in a new measurement, due to delays or sounds from the capacitor. After the guard band time, the next LED emitter is turned on, with a wavelength sensitive to hemoglobin 943. The 911 silicone detector is again used as described above to carry out the measurement.

When this measure related to

<img file="MX347286B_D0025.tif" />

hemoglobin, the LED emitter 943 turns off, and another guard band time elapses. Subsequently, the LED emitter, which is sensitive to the water concentration 945, is turned on. The LED emitter 945 generates a wavelength that corresponds to the InGaAs photodetector 913. During this measurement, i the gain of the silicone potentiometer 188 is set to zero, and the gain of the InGaAs potentiometer 188 is adjusted to the required value to facilitate a DC measurement proportional to the amplitude of the channel.

As described above, the ratio of the oxygen measurements to the hemoglobin measurements, allows the calculation of the oxygen saturation of the blood as a percentage, and the ratio of the hemoglobin measurements to the water concentration measurements, allows the calculation of the percentage of red blood cells per unit blood volume (for example "Hematocrits"). These calculations are carried out via microcontroller 182, transmitted via a serial communications chip (eg, a level converter commercially available from Future Technology Devices International, Ltd., an "FTDI level converter") 198, and a transfer to an external computer device via a serial communications cable, such as USB cable 158. It will be appreciated that the external computing device may be a conventional personal computer with suitable software, or other types of hardware.

IMPI »

MSXlCAN INSTITUTE

Dt FAOflSDAD

INDUCTUAL J device incorporating USB hosting capabilities such as a PDA (personal digital assistant) or similar type of device with the ability to run software for processing a data stream transferred from the sensor holder assembly 34.

The operation of the microcontroller 182, with respect to the timing of the operation of the LED emitters and photodetectors, is described in greater detail with respect to FIG. 10. The "Wavelength λ-1" corresponds to the LED emitter that generates a wavelength sensitive to oxygen, the "Wavelength A-2" corresponds to the LED emitter that generates a wavelength sensitive to hemoglobin, and the "Longitude wavelength Λ-3 ”corresponds to the LED emitter that generates a wavelength sensitive to water concentration. As previously described with respect to FIG. 9, a first LED 941 emitter corresponding to the "Wavelength λ-1" is turned on, and the Silicon Channel is activated simultaneously by appropriate adjustment of the gains of digital potentiometers 188 (see Trace A and Trace B). Subsequently, the first LED emitter is turned off, and the Silicon channel is deactivated, and after a “protection band”, a second LED emitter is turned on corresponding to the “Wavelength λ-2, and at the same time the Silicone channel is activated simultaneously. Similarly, after the second LED emitter is turned off, the signal channel is deactivated.

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MUICANO INSTITUTE

M THE INDUSTRIAL NOMSBAD

<img file="MX347286B_D0026.tif" />

Silicon, and after another “protection band”, a third LED emitter is turned on corresponding to the “Wavelength λ

3 ”, while the InGaAs channel is activated. Figure 10 further illustrates in trace C, a data burst control timing. Due to the sensitivity of analog signal conditioning circuits, it is desirable to transmit digital data through the transfer port during the guard band, so that the transmission of digital data does not interfere with the acquisition and conditioning of analog signals. without processing. Figure 10 further illustrates that the LED current required to operate each LED emitter may be different (as seen in Trace B). This process of time-domain multiplexing of the LED emitters and the receiving channels is repeated throughout the course of data acquisition.

In a further embodiment, as illustrated in the functional block diagram of Figure 11, the calculation of blood properties and the generation of control signals rather takes place on an external device, such as a personal computer. standalone, or networked, and the sensor holder assembly 34 is responsible for the acquisition of raw digital data (i.e., raw analog data generated by photodetectors that has been conditioned and converted to digital format). The sensor holder assembly 34 of this mode included the emitters

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MEKJCAN INSTITUTE

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<img file="MX347286B_D0027.tif" />

LEDs 941, 943, 945, photodetectors 911, 913, Silicon and InGaAs channels, signal conditioning circuit 970 (including amplifiers 186, digital potentiometers 88, and filter / detection circuit block 921 as described above with respect to FIG. 9), an analog-to-digital converter to 931, and a digital signaling cable 980 connected to an external computing device. Sensor clip assembly 34 receives control signals from the receiver, and transfers data through connectors 960, and receives control signals from the emitter through connectors 961. Sensor clip assembly 34 also receives power from the 980 digital signaling cable. It will be appreciated that the sensor holder assembly 34 of this embodiment also reduces the transmission distance of the analog signals, which reduces the amount of noise introduced by the analog transmission and allows adequate signal-to-noise ratios to be achieved, in a lower energy level, as described above.

Returning to a further embodiment of the sensor holder assembly 34 illustrated in Figures 8 and 9, the sensor holder assembly 34 is connected via USB cable 158 to a computer programmed with software to receive data from the sensor holder assembly. 34 and display them on a screen. Because the raw data is collected, it is converted to digital signals and

<img file="MX347286B_D0028.tif" />

calculated in the sensor holder assembly 34, the computer does not undergo any calibration requirements, and does not need to include ratiometric calculation capabilities. Figure 12 provides an example demo software interface that allows the user to view the data received from the sensor holder assembly 34, as well as to issue commands to the sensor holder assembly 34 (in accordance with the computer-executable instructions being used. carried out by a software application that is being run by the computer). It will be appreciated that the interface of the demo software of figure 12 is merely an example and that the configuration and the types of information and / or options presented to the user can be varied. For example, business software applications designed for a business user may include less information as a business user may not need to use the detailed status information or view the received data stream.

The "COM Port" section 1001 of the interface allows the user to select a COM number that corresponds to the sensor holder assembly 34 with which the user wishes to interact. A simple computer that has multiple USB ports can accommodate more than one of the sensor clip assemblies 34, and therefore, multiple sensor clip assemblies can be connected to the computer at the same time. It will be appreciated that in a modality

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MJJUCAN INSTITUTE

M THE INDUSTRIAL RMSKUIAD

<img file="MX347286B_D0029.tif" />

Additionally, the software interface can allow the required information from multiple sensor clip assemblies to be viewed simultaneously, as well as allows simultaneous control of multiple sensor clip assemblies.

In a further embodiment, the computer to which the sensor holder assembly 34 is connected can be wirelessly connected to a computer running the software application to control one or more sensor holder assemblies remotely via of a wireless connection.

The "Log File" section 1003 of the interface allows the user to store data received from the sensor holder assembly 34 in a log file at a user-designed (or automatically generated) location. The user can toggle this activation or deactivation of the logging function by checking the box after the word “Log”.

The "Input Data" section 1005 of the interface displays the input data of the sensor holder assemblies 34 in an example format similar to the format described in Table I above. The "Analyzed Data" section 1007 of the interface, displays a unit ID and filter ID that correspond to the sensor holder assembly 34 from which the data is received, as well as the "Count", "Met" information. , “Sat, and“ Status ”, which corresponds to a count value, a

IMPI

ΜΤΠΤυΤΟ MHICANO

K THE nOfeOAD rwnumiAi

<img file="MX347286B_D0030.tif" />

Hematocrit value, an oxygen saturation value, and status information, respectively. The “Count” value is an approximate time counter. The user can check the “Count Flag” box to cause the count value to increment in one second intervals indefinitely. If the “Count Flag” box is not checked, the count value will have an extension after it reaches a value of 9. The "Status Bits" section 1009 of the interface shows whether certain products fit or clear based on the "Status" information received from the sensor holder assembly 34.

The 1011 “Control Functions” section of the interface provides few commands that the user can issue to the sensor holder assembly 34. The “Verify” button provides the user with an option to verify or recalibrate the sensor holder assembly. 3. 4. If the user chooses to verify that the device is still operating within a suitable range, the sensor holder assembly 34 must be attached to the verification filter that corresponds only to the sensor holder assembly 34 in order for the verification to be accurate. . As described above, with respect to Figure 7, if the verification function fails twice, then the system is out of service and eligible for field recalibration. Before the system can be recalibrated, the screen will display

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a quick question to the user to confirm the ID of the verification filter to which the sensor holder assembly was attached. If the sensor holder assembly is clamped to the wrong verification filter, recalibration cannot be performed.

The "Turn LEDs Off" button turns the LED emitters off (and changes to a "Turn LEDs On" button after the user has chosen to turn the LEDs off). Manual shutdown of all LEDs when the sensor holder assembly 34 is not in use, prolongs the service life of the sensor holder assembly 34. The "Reset" button resets sensor holder assembly 34 (ie to step 701 of the process illustrated in Figure 7) without resetting the port connection (ie, a reset does not re-enumerate sensor holder assembly 34 in the USB port or otherwise affects the USB connection).

The “Patient Run” 1013 section of the interface provides the user with the “Start Run” option, which causes the application to start recording the values ​​of the percentage of change in blood volume (% Change BV), hematocrit values ​​( Hct), and oxygen saturation (Sat) once every minute in a delimited text file, which can be manipulated, for example, through a spreadsheet or database application (other than the log file shown in the “Log File 1003 section of the interface). The

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The file name is displayed in the window after the “Start Run” or “End Run” button. Figure 12 shows a patient run that is currently in progress, and therefore, the "Start Run" button had previously been pressed, and an "End Run" button is currently being displayed to the user. The graphs in the "Patient Run" section 1013 of the screen are a graphical representation of the data stored in the text file, and allow the user to visually monitor the% BV, Hct, and Sat values ​​over time.

In the “Exit” section 1015 of the interface, the user can exit the software application by clicking on the “Exit” button.

Figures 13A through F illustrate an example user interface of a commercial user software application of a sensor holder assembly 34 pertaining to verification and recalibration. Figure 13A shows the user interface presented by the user after the user has chosen to verify the accuracy of a sensor holder assembly 34 and the verification has failed (that is, the readings for the sensor holder assembly 34 are missing. within a predetermined tolerance range). As shown in Figure 13A, the user is notified that the accuracy check has failed, and is advised to ensure that the sensor holder assembly is securely attached.

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appropriate to the verification filter, and verification is clean. Then “OK” and try to verify the accuracy of sensor 34, and it fails again, the interface shown in figure 13B is presented, which notifies the user that the verification has failed, and provides the user with the option of attempting a calibration in the field. . If the user selects “Yes” in the interface shown in figure 13B, the user is taken to the screen shown in figure 13C, which notifies the user that they will need to enter the identification code that corresponds to the verification filter (which is a serial number that can be obtained from the verification filter itself). After the user presses "OK", the user is prompted to enter the identification code as shown in Figure 13D. The software then compares the entered identification code with an identification code that corresponds to the sensor holder assembly 34 obtained from the sensor holder assembly 34 or previously stored in the external computing device, and if a match is found, the user you are notified that the entered identification code has been accepted, as shown in Figure 13E. After the user presses "OK" on the screen shown in Figure 13E, the sensor holder assembly 34 is recalibrated in the field, and the software once again tries to

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verify accuracy of sensor holder assembly 34.

If this verification fails after recalibration in the field, the user will be notified that the sensor holder assembly 34 (called a “Crit-Line sensor holder” in this example), needs to be replaced, as shown in Fig. Figure 13F. The user can attempt additional field recalibrations.

It will be appreciated that, with respect to the embodiment of the sensor holder assembly illustrated in Figure 11, the 10 software applications described above with respect to Figures 12 and 13A through 13F can be modified to receive raw digital data from the sensor holder assembly 34, perform ratiometric calculations based on received raw digital data, display similar results 15 to a user, and be verified and recalibrated as described above.

Although the modalities described above have focused on data collection regarding the values ​​of percent change in blood volume, hematocrit values, and oxygen saturation, it will be appreciated that other types of LED emitters can be used. paired with the same or other types of photodetector diodes, to measure other types of parameters.

All references, including publications, 25 patent applications and patents, mentioned herein are

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incorporated into the present invention by reference, to the same extent as if each were individually and specifically indicated as incorporated by reference, and are set forth in their entirety in the present invention.

The use of the terms "a" and "one, an" and "the, the" and similar references within the context of describing the present invention (especially within the context of the claims that follow) will be construed to cover both singular and plural, unless otherwise stated or clearly contraindicated in context. The terms "comprising", "having", "including" and "containing" will be construed as open-ended terms (ie meaning "including but not limited to") unless otherwise indicated. . Mention of ranges of values ​​in the present invention are intended merely to serve as a handy method of making individual reference to each separate value that falls within the range, unless otherwise indicated in the present invention, and each separate value is incorporated into the specification as if it were mentioned individually. All of the methods described herein may be carried out in any suitable order unless otherwise indicated in the present invention, or clearly contraindicated in context. The use of any and all examples, or example language (eg "as") provided herein, is merely intended to better illuminate the present invention, and does not pose a limitation on the scope thereof, unless otherwise stated. claim otherwise. Language in the specification should not be construed as indicating any item not claimed as essential to the practice of the present invention.

Preferred embodiments of the present invention are described therein, including the best mode known to the inventors for carrying out the present invention. Variations of such preferred embodiments may be appreciated by those skilled in the art upon reading the foregoing description. The inventors expect those skilled in the art to employ such variations as appropriate, and the inventors intend the present invention to be practiced in a manner other than that specifically described herein. Accordingly, the present invention includes all modifications and equivalents of the subject matter mentioned in the appended claims, as permitted by applicable law. Furthermore, any combination of the elements described above in all possible variations thereof is encompassed by the present invention, unless otherwise stated or clearly contraindicated in the context of this document.