Abstract:
Methods and apparatuses including determining a calibration parameter associated with a detected analyte value, calibrating the analyte value based on the calibration parameter, and dynamically updating the calibration parameter are disclosed. Also provided are systems, kits, and computer program products.

Description:
RELATED APPLICATIONS 
       [0001]    The present application is a continuation of pending U.S. patent application Ser. No. 11/537,991 filed Oct. 2, 2006, entitled “Method and System for Dynamically Updating Calibration Parameters for an Analyte Sensor”, the disclosure of which is incorporated herein by reference for all purposes. 
     
    
     BACKGROUND 
       [0002]    Analyte, e.g., glucose monitoring systems including continuous and discrete monitoring systems generally include a small, lightweight battery powered and microprocessor controlled system which is configured to detect signals proportional to the corresponding measured glucose levels using an electrometer, and RF signals to transmit the collected data. One aspect of certain analyte monitoring systems include a transcutaneous or subcutaneous analyte sensor configuration which is, for example, partially mounted on the skin of a subject whose analyte level is to be monitored. The sensor cell may use a two or three-electrode (work, reference and counter electrodes) configuration driven by a controlled potential (potentiostat) analog circuit connected through a contact system. 
         [0003]    The analyte sensor may be configured so that a portion thereof is placed under the skin of the patient so as to detect the analyte levels of the patient, and another portion of segment of the analyte sensor that is in communication with the transmitter unit. The transmitter unit is configured to transmit the analyte levels detected by the sensor over a wireless communication link such as an RF (radio frequency) communication link to a receiver/monitor unit. The receiver/monitor unit performs data analysis, among others on the received analyte levels to generate information pertaining to the monitored analyte levels. 
         [0004]    To obtain accurate data from the analyte sensor, calibration is necessary. Typically, blood glucose measurements are periodically obtained using, for example, a blood glucose meter, and the measured blood glucose values are used to calibrate the sensors. Indeed, the patient must calibrate each new analyte sensor using for example, capillary blood glucose measurements. Due to a lag factor between the monitored data and the measured blood glucose values, an error is typically introduced in the monitored data. 
         [0005]    In view of the foregoing, it would be desirable to have a method and system for calibrating analyte sensors of an analyte monitoring system to minimize the lag error and compensation of such lag errors in analyte monitoring systems. 
       SUMMARY OF THE INVENTION 
       [0006]    In one embodiment, a method including determining a calibration parameter associated with a detected analyte value, calibrating the analyte value based on the calibration parameter, and dynamically updating the calibration parameter is disclosed. 
         [0007]    These and other objects, features and advantages of the present invention will become more fully apparent from the following detailed description of the embodiments, the appended claims and the accompanying drawings. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0008]      FIG. 1  illustrates a block diagram of a data monitoring and management system for practicing one or more embodiments of the present invention; 
           [0009]      FIG. 2  is a block diagram of the transmitter unit of the data monitoring and management system shown in  FIG. 1  in accordance with one embodiment of the present invention; 
           [0010]      FIG. 3  is a block diagram of the receiver/monitor unit of the data monitoring and management system shown in  FIG. 1  in accordance with one embodiment of the present invention; 
           [0011]      FIG. 4  is a flowchart illustrating an overall dynamically updating calibration in accordance with one embodiment of the present invention; 
           [0012]      FIG. 5  is a flowchart illustrating the lag correction and calibration routine of the overall dynamically updating calibration shown in  FIG. 4  in accordance with one embodiment of the present invention; 
           [0013]      FIG. 6  is a flowchart illustrating the lag correction and dynamically updating calibration routine of the overall dynamically updating calibration shown in  FIG. 4  in accordance with one embodiment of the present invention; 
           [0014]      FIG. 7  illustrates an example of the lag corrected and calibrated sensor data in accordance with one embodiment of the present invention; and 
           [0015]      FIG. 8  illustrates a further example of the lag corrected and calibrated sensor data in accordance with one embodiment of the present invention. 
       
    
    
     DETAILED DESCRIPTION 
       [0016]    As described in further detail below, in accordance with the various embodiments of the present invention, there is provided a method and system for calibration of analyte sensors to reduce errors in the sensor measurements. In particular, within the scope of the present invention, there are provided method and system for calibrating subcutaneous or transcutaneously positioned analyte sensors to compensate for lag errors associated with the estimated sensor sensitivity. 
         [0017]      FIG. 1  illustrates a data monitoring and management system such as, for example, analyte (e.g., glucose) monitoring system  100  in accordance with one embodiment of the present invention. The subject invention is further described primarily with respect to a glucose monitoring system for convenience and such description is in no way intended to limit the scope of the invention. It is to be understood that the analyte monitoring system may be configured to monitor a variety of analytes, e.g., lactate, and the like. 
         [0018]    Analytes that may be monitored include, for example, acetyl choline, amylase, bilirubin, cholesterol, chorionic gonadotropin, creatine kinase (e.g., CK-MB), creatine, DNA, fructosamine, glucose, glutamine, growth hormones, hormones, ketones, lactate, peroxide, prostate-specific antigen, prothrombin, RNA, thyroid stimulating hormone, and troponin. The concentration of drugs, such as, for example, antibiotics (e.g., gentamicin, vancomycin, and the like), digitoxin, digoxin, drugs of abuse, theophylline, and warfarin, may also be monitored. 
         [0019]    The analyte monitoring system  100  includes a sensor  101 , a transmitter unit  102  coupled to the sensor  101 , and a primary receiver unit  104  which is configured to communicate with the transmitter unit  102  via a communication link  103 . The primary receiver unit  104  may be further configured to transmit data to a data processing terminal  105  for evaluating the data received by the primary receiver unit  104 . Moreover, the data processing terminal in one embodiment may be configured to receive data directly from the transmitter unit  102  via a communication link  106  which may optionally be configured for bi-directional communication. 
         [0020]    Also shown in  FIG. 1  is a secondary receiver unit  106  which is operatively coupled to the communication link and configured to receive data transmitted from the transmitter unit  102 . Moreover, as shown in the Figure, the secondary receiver unit  106  is configured to communicate with the primary receiver unit  104  as well as the data processing terminal  105 . Indeed, the secondary receiver unit  106  may be configured for bi-directional wireless communication with each of the primary receiver unit  104  and the data processing terminal  105 . As discussed in further detail below, in one embodiment of the present invention, the secondary receiver unit  106  may be configured to include a limited number of functions and features as compared with the primary receiver unit  104 . As such, the secondary receiver unit  106  may be configured substantially in a smaller compact housing or embodied in a device such as a wrist watch, for example. Alternatively, the secondary receiver unit  106  may be configured with the same or substantially similar functionality as the primary receiver unit  104 , and may be configured to be used in conjunction with a docking cradle unit for placement by bedside, for night time monitoring, and/or bi-directional communication device. 
         [0021]    Only one sensor  101 , transmitter unit  102 , communication link  103 , and data processing terminal  105  are shown in the embodiment of the analyte monitoring system  100  illustrated in  FIG. 1 . However, it will be appreciated by one of ordinary skill in the art that the analyte monitoring system  100  may include one or more sensor  101 , transmitter unit  102 , communication link  103 , and data processing terminal  105 . Moreover, within the scope of the present invention, the analyte monitoring system  100  may be a continuous monitoring system, or semi-continuous, or a discrete monitoring system. In a multi-component environment, each device is configured to be uniquely identified by each of the other devices in the system so that communication conflict is readily resolved between the various components within the analyte monitoring system  100 . 
         [0022]    In one embodiment of the present invention, the sensor  101  is physically positioned in or on the body of a user whose analyte level is being monitored. The sensor  101  may be configured to continuously sample the analyte level of the user and convert the sampled analyte level into a corresponding data signal for transmission by the transmitter unit  102 . In one embodiment, the transmitter unit  102  is mounted on the sensor  101  so that both devices are positioned on the user&#39;s body. The transmitter unit  102  performs data processing such as filtering and encoding on data signals, each of which corresponds to a sampled analyte level of the user, for transmission to the primary receiver unit  104  via the communication link  103 . 
         [0023]    In one embodiment, the analyte monitoring system  100  is configured as a one-way RF communication path from the transmitter unit  102  to the primary receiver unit  104 . In such embodiment, the transmitter unit  102  transmits the sampled data signals received from the sensor  101  without acknowledgement from the primary receiver unit  104  that the transmitted sampled data signals have been received. For example, the transmitter unit  102  may be configured to transmit the encoded sampled data signals at a fixed rate (e.g., at one minute intervals) after the completion of the initial power on procedure. Likewise, the primary receiver unit  104  may be configured to detect such transmitted encoded sampled data signals at predetermined time intervals. Alternatively, the analyte monitoring system  100  may be configured with a bi-directional RF (or otherwise) communication between the transmitter unit  102  and the primary receiver unit  104 . 
         [0024]    Additionally, in one aspect, the primary receiver unit  104  may include two sections. The first section is an analog interface section that is configured to communicate with the transmitter unit  102  via the communication link  103 . In one embodiment, the analog interface section may include an RF receiver and an antenna for receiving and amplifying the data signals from the transmitter unit  102 , which are thereafter, demodulated with a local oscillator and filtered through a band-pass filter. The second section of the primary receiver unit  104  is a data processing section which is configured to process the data signals received from the transmitter unit  102  such as by performing data decoding, error detection and correction, data clock generation, and data bit recovery. 
         [0025]    In operation, upon completing the power-on procedure, the primary receiver unit  104  is configured to detect the presence of the transmitter unit  102  within its range based on, for example, the strength of the detected data signals received from the transmitter unit  102  or a predetermined transmitter identification information. Upon successful synchronization with the corresponding transmitter unit  102 , the primary receiver unit  104  is configured to begin receiving from the transmitter unit  102  data signals corresponding to the user&#39;s detected analyte level. More specifically, the primary receiver unit  104  in one embodiment is configured to perform synchronized time hopping with the corresponding synchronized transmitter unit  102  via the communication link  103  to obtain the user&#39;s detected analyte level. 
         [0026]    Referring again to  FIG. 1 , the data processing terminal  105  may include a personal computer, a portable computer such as a laptop or a handheld device (e.g., personal digital assistants (PDAs)), and the like, each of which may be configured for data communication with the receiver via a wired or a wireless connection. Additionally, the data processing terminal  105  may further be connected to a data network (not shown) for storing, retrieving and updating data corresponding to the detected analyte level of the user. 
         [0027]    Within the scope of the present invention, the data processing terminal  105  may include an infusion device such as an insulin infusion pump or the like, which may be configured to administer insulin to patients, and which may be configured to communicate with the receiver unit  104  for receiving, among others, the measured analyte level. Alternatively, the receiver unit  104  may be configured to integrate an infusion device therein so that the receiver unit  104  is configured to administer insulin therapy to patients, for example, for administering and modifying basal profiles, as well as for determining appropriate boluses for administration based on, among others, the detected analyte levels received from the transmitter unit  102 . 
         [0028]    Additionally, the transmitter unit  102 , the primary receiver unit  104  and the data processing terminal  105  may each be configured for bi-directional wireless communication such that each of the transmitter unit  102 , the primary receiver unit  104  and the data processing terminal  105  may be configured to communicate (that is, transmit data to and receive data from) with each other via the wireless communication link  103 . More specifically, the data processing terminal  105  may in one embodiment be configured to receive data directly from the transmitter unit  102  via the communication link  106 , where the communication link  106 , as described above, may be configured for bi-directional communication. 
         [0029]    In this embodiment, the data processing terminal  105  which may include an insulin pump, may be configured to receive the analyte signals from the transmitter unit  102 , and thus, incorporate the functions of the receiver  103  including data processing for managing the patient&#39;s insulin therapy and analyte monitoring. In one embodiment, the communication link  103  may include one or more of an RF communication protocol, an infrared communication protocol, a Bluetooth enabled communication protocol, an 802.11x wireless communication protocol, or an equivalent wireless communication protocol which would allow secure, wireless communication of several units (for example, per HIPPA requirements) while avoiding potential data collision and interference. 
         [0030]      FIG. 2  is a block diagram of the transmitter of the data monitoring and detection system shown in  FIG. 1  in accordance with one embodiment of the present invention. Referring to the Figure, the transmitter unit  102  in one embodiment includes an analog interface  201  configured to communicate with the sensor  101  ( FIG. 1 ), a user input  202 , and a temperature detection section  203 , each of which is operatively coupled to a transmitter processor  204  such as a central processing unit (CPU). As can be seen from  FIG. 2 , there are provided four contacts, three of which are electrodes—work electrode (W)  210 , guard contact (G)  211 , reference electrode (R)  212 , and counter electrode (C)  213 , each operatively coupled to the analog interface  201  of the transmitter unit  102  for connection to the sensor unit  201  ( FIG. 1 ). In one embodiment, each of the work electrode (W)  210 , guard contact (G)  211 , reference electrode (R)  212 , and counter electrode (C)  213  may be made using a conductive material that is either printed or etched, for example, such as carbon which may be printed, or metal foil (e.g., gold) which may be etched. 
         [0031]    Further shown in  FIG. 2  are a transmitter serial communication section  205  and an RF transmitter  206 , each of which is also operatively coupled to the transmitter processor  204 . Moreover, a power supply  207  such as a battery is also provided in the transmitter unit  102  to provide the necessary power for the transmitter unit  102 . Additionally, as can be seen from the Figure, clock  208  is provided to, among others, supply real time information to the transmitter processor  204 . 
         [0032]    In one embodiment, a unidirectional input path is established from the sensor  101  ( FIG. 1 ) and/or manufacturing and testing equipment to the analog interface  201  of the transmitter unit  102 , while a unidirectional output is established from the output of the RF transmitter  206  of the transmitter unit  102  for transmission to the primary receiver unit  104 . In this manner, a data path is shown in  FIG. 2  between the aforementioned unidirectional input and output via a dedicated link  209  from the analog interface  201  to serial communication section  205 , thereafter to the processor  204 , and then to the RF transmitter  206 . As such, in one embodiment, via the data path described above, the transmitter unit  102  is configured to transmit to the primary receiver unit  104  ( FIG. 1 ), via the communication link  103  ( FIG. 1 ), processed and encoded data signals received from the sensor  101  ( FIG. 1 ). Additionally, the unidirectional communication data path between the analog interface  201  and the RF transmitter  206  discussed above allows for the configuration of the transmitter unit  102  for operation upon completion of the manufacturing process as well as for direct communication for diagnostic and testing purposes. 
         [0033]    As discussed above, the transmitter processor  204  is configured to transmit control signals to the various sections of the transmitter unit  102  during the operation of the transmitter unit  102 . In one embodiment, the transmitter processor  204  also includes a memory (not shown) for storing data such as the identification information for the transmitter unit  102 , as well as the data signals received from the sensor  101 . The stored information may be retrieved and processed for transmission to the primary receiver unit  104  under the control of the transmitter processor  204 . Furthermore, the power supply  207  may include a commercially available battery. 
         [0034]    The transmitter unit  102  is also configured such that the power supply section  207  is capable of providing power to the transmitter for a minimum of about three months of continuous operation after having been stored for about eighteen months in a low-power (non-operating) mode. In one embodiment, this may be achieved by the transmitter processor  204  operating in low power modes in the non-operating state, for example, drawing no more than approximately 1 μA of current. Indeed, in one embodiment, the final step during the manufacturing process of the transmitter unit  102  may place the transmitter unit  102  in the lower power, non-operating state (i.e., post-manufacture sleep mode). In this manner, the shelf life of the transmitter unit  102  may be significantly improved. Moreover, as shown in  FIG. 2 , while the power supply unit  207  is shown as coupled to the processor  204 , and as such, the processor  204  is configured to provide control of the power supply unit  207 , it should be noted that within the scope of the present invention, the power supply unit  207  is configured to provide the necessary power to each of the components of the transmitter unit  102  shown in  FIG. 2 . 
         [0035]    Referring back to  FIG. 2 , the power supply section  207  of the transmitter unit  102  in one embodiment may include a rechargeable battery unit that may be recharged by a separate power supply recharging unit (for example, provided in the receiver unit  104 ) so that the transmitter unit  102  may be powered for a longer period of usage time. Moreover, in one embodiment, the transmitter unit  102  may be configured without a battery in the power supply section  207 , in which case the transmitter unit  102  may be configured to receive power from an external power supply source (for example, a battery) as discussed in further detail below. 
         [0036]    Referring yet again to  FIG. 2 , the temperature detection section  203  of the transmitter unit  102  is configured to monitor the temperature of the skin near the sensor insertion site. The temperature reading is used to adjust the analyte readings obtained from the analog interface  201 . The RF transmitter  206  of the transmitter unit  102  may be configured for operation in the frequency band of 315 MHz to 322 MHz, for example, in the United States. Further, in one embodiment, the RF transmitter  206  is configured to modulate the carrier frequency by performing Frequency Shift Keying and Manchester encoding. In one embodiment, the data transmission rate is 19,200 symbols per second, with a minimum transmission range for communication with the primary receiver unit  104 . 
         [0037]    Referring yet again to  FIG. 2 , also shown is a leak detection circuit  214  coupled to the guard electrode (G)  211  and the processor  204  in the transmitter unit  102  of the data monitoring and management system  100 . The leak detection circuit  214  in accordance with one embodiment of the present invention may be configured to detect leakage current in the sensor  101  to determine whether the measured sensor data are corrupt or whether the measured data from the sensor  101  is accurate. 
         [0038]    Additional detailed description of the continuous analyte monitoring system, its various components including the functional descriptions of the transmitter are provided in U.S. Pat. No. 6,175,752 issued Jan. 16, 2001 entitled “Analyte Monitoring Device and Methods of Use”, and in application Ser. No. 10/745,878 filed Dec. 26, 2003 entitled “Continuous Glucose Monitoring System and Methods of Use”, each assigned to the Assignee of the present application. 
         [0039]      FIG. 3  is a block diagram of the receiver/monitor unit of the data monitoring and management system shown in  FIG. 1  in accordance with one embodiment of the present invention. Referring to  FIG. 3 , the primary receiver unit  104  includes a blood glucose test strip interface  301 , an RF receiver  302 , an input  303 , a temperature detection section  304 , and a clock  305 , each of which is operatively coupled to a receiver processor  307 . As can be further seen from the Figure, the primary receiver unit  104  also includes a power supply  306  operatively coupled to a power conversion and monitoring section  308 . Further, the power conversion and monitoring section  308  is also coupled to the receiver processor  307 . Moreover, also shown are a receiver serial communication section  309 , and an output  310 , each operatively coupled to the receiver processor  307 . 
         [0040]    In one embodiment, the test strip interface  301  includes a glucose level testing portion to receive a manual insertion of a glucose test strip, and thereby determine and display the glucose level of the test strip on the output  310  of the primary receiver unit  104 . This manual testing of glucose can be used to calibrate sensor  101 . The RF receiver  302  is configured to communicate, via the communication link  103  ( FIG. 1 ) with the RF transmitter  206  of the transmitter unit  102 , to receive encoded data signals from the transmitter unit  102  for, among others, signal mixing, demodulation, and other data processing. The input  303  of the primary receiver unit  104  is configured to allow the user to enter information into the primary receiver unit  104  as needed. In one aspect, the input  303  may include one or more keys of a keypad, a touch-sensitive screen, or a voice-activated input command unit. The temperature detection section  304  is configured to provide temperature information of the primary receiver unit  104  to the receiver processor  307 , while the clock  305  provides, among others, real time information to the receiver processor  307 . 
         [0041]    Each of the various components of the primary receiver unit  104  shown in  FIG. 3  is powered by the power supply  306  which, in one embodiment, includes a battery. Furthermore, the power conversion and monitoring section  308  is configured to monitor the power usage by the various components in the primary receiver unit  104  for effective power management and to alert the user, for example, in the event of power usage which renders the primary receiver unit  104  in sub-optimal operating conditions. An example of such sub-optimal operating condition may include, for example, operating the vibration output mode (as discussed below) for a period of time thus substantially draining the power supply  306  while the processor  307  (thus, the primary receiver unit  104 ) is turned on. Moreover, the power conversion and monitoring section  308  may additionally be configured to include a reverse polarity protection circuit such as a field effect transistor (FET) configured as a battery activated switch. 
         [0042]    The serial communication section  309  in the primary receiver unit  104  is configured to provide a bi-directional communication path from the testing and/or manufacturing equipment for, among others, initialization, testing, and configuration of the primary receiver unit  104 . Serial communication section  104  can also be used to upload data to a computer, such as time-stamped blood glucose data. The communication link with an external device (not shown) can be made, for example, by cable, infrared (IR) or RF link. The output  310  of the primary receiver unit  104  is configured to provide, among others, a graphical user interface (GUI) such as a liquid crystal display (LCD) for displaying information. Additionally, the output  310  may also include an integrated speaker for outputting audible signals as well as to provide vibration output as commonly found in handheld electronic devices, such as mobile telephones presently available. In a further embodiment, the primary receiver unit  104  also includes an electro-luminescent lamp configured to provide backlighting to the output  310  for output visual display in dark ambient surroundings. 
         [0043]    Referring back to  FIG. 3 , the primary receiver unit  104  in one embodiment may also include a storage section such as a programmable, non-volatile memory device as part of the processor  307 , or provided separately in the primary receiver unit  104 , operatively coupled to the processor  307 . The processor  307  is further configured to perform Manchester decoding as well as error detection and correction upon the encoded data signals received from the transmitter unit  102  via the communication link  103 . 
         [0044]      FIG. 4  is a flowchart illustrating an overall dynamically updating calibration in accordance with one embodiment of the present invention. Referring to  FIG. 4 , a counter such as a calibration counter is triggered to perform calibration of the monitored data such as the analyte data received from the transmitter unit  102  ( FIG. 1 ). In one embodiment, the calibration counter may include a timer or a clock which may be configured to prompt the user or the patient to initiate the acquisition of reference data at a predetermined time intervals. When the calibration counter is initially triggered, the time counter T is initialized to zero (0). Thereafter, a calibration parameter is determined based on, for example, the acquired reference data and the monitored sensor data at time T=0. Moreover, in one embodiment, the monitored sensor data may be updated based on the calibration parameter. In one embodiment, the calibration parameter may include a sensor sensitivity value associated with the analyte sensor  101  ( FIG. 1 ) configured to monitor the analyte levels of the patient. 
         [0045]    As described in further detail below, for example, in conjunction with  FIG. 5 , in particular embodiments, during the initial calibration stage at T=0, a reference glucose value is determined, for example, such as a capillary blood glucose value using a blood glucose meter such as FREESTYLE® meter or PRECISION XTRA™ meter available from Abbott Diabetes Care Inc., Alameda, Calif. In addition, the monitored sensor data at or near the calibration time (T=0) is retrieved which may include the monitored sensor data at time T=T−1, at time T=T+1, or any other suitable time period (for example, from the processing and storage unit  307  ( FIG. 3 ) of the receiver unit  104  ( FIG. 1 ). 
         [0046]    More specifically, in one embodiment, the monitored sensor data at the calibration time (T=0) may include one or more monitored sensor data in addition to the monitored sensor data point at the calibration time (T=0). That is, in one embodiment, the monitored sensor data at the calibration time (T=0) may include all monitored sensor data available for retrieval from the receiver unit  104  ( FIG. 1 ) at the calibration time (T=0). For example, to reduce the contribution of noise in the measured sensor data, an average of the two most recent sensor data may be associated with the monitored sensor data at the calibration time (T=0). 
         [0047]    Broadly, within the scope of the present disclosure, the monitored sensor data at a predetermined time may include, in particular embodiments, an estimate of the sensor data at the predetermined time as determined by the one or more filters which may be configured to use the monitored sensor data up to and including the data point at the predetermined time (for example, up to the data point at calibration time (T=0)). In one embodiment, one or more filters such as a finite impulse response (FIR) filter may be used to determine the best estimate at a predetermined time using a finite window of monitored sensor data up to the current or most recent monitored sensor data point. 
         [0048]    Referring back to  FIG. 4 , after determining the calibration parameter and updating the monitored data at the calibration time (T=0), the counter is incremented by one (1), and dynamic, real-time update of the calibration parameter is performed. In one embodiment, the counter may be configured to increment by one with each reception of sensor data from the transmitter unit  102  ( FIG. 1 ). After dynamically updating the calibration parameter at the subsequent incremented time (T=1), it is determined whether the counter has reached a predetermined count (for example, set at seven (7)). If it is determined that the counter has not reached the predetermined count, then the routine in one embodiment returns to step  430  where the counter is incremented by one (1) and the dynamically updating calibration parameter and monitored sensor data is performed for monitored data at the second subsequent incremented time (T=2). 
         [0049]    On the other hand, if it is determined that the counter has reached the predetermined count, then in one embodiment, subsequent monitored sensor data may be updated based on the dynamically updated calibration parameter and/or updated monitored sensor data. Thereafter, in particular embodiments, it is determined whether further or subsequent lag correction will likely not yield more accurate monitored data value (or with less errors). Therefore, in one embodiment, the routine terminates and awaits for the subsequent calibration time, for example, to repeat the processes described above in conjunction with  FIG. 4 . 
         [0050]    In this manner, within the scope of the present disclosure, there are provided methods and system for dynamically, and in particular embodiments, in real-time, obtaining reference data at a first predetermined time, receiving measured data prior to and including (or near) the first predetermined time, calculating a first calibration parameter (or parameters) using the data, calibrating the measured data based on the calibration parameter, receiving measured data at a second predetermined time, updating the calibration parameter based on all of the previous data and the newly received measured data, calibrating the newly received measured data based on the updated calibration parameter, and repeating a number of time the process of receiving new measurement data, updating the calibration parameter, calibrating the newly received measurement data, and calibrating any newly received measurement data with the fully updated calibration parameter. 
         [0051]    A method in a further embodiment may include performing lag compensation on the measured data that is used to update the calibration parameter. Lag compensation may optionally be performed on the measured data that is calibrated. A method in a further embodiment includes filtering the measured data that is used to update the calibration parameter. 
         [0052]      FIG. 5  is a flowchart illustrating the lag correction and calibration routine of the overall dynamically updating calibration shown in  FIG. 4  in accordance with one embodiment of the present invention. Referring to  FIG. 5 , the determination of calibration parameter and updating the monitored analyte level at the calibration time (T=0) is described in further detail. More specifically, in one embodiment, a capillary blood glucose value is determined at the calibration time (T=0), and the monitored analyte value at the calibration time is retrieved from the receiver unit  104  of the monitoring system  100  ( FIG. 1 ). 
         [0053]    Thereafter, a rate of change of the monitored data at the calibration time (T=0) is determined. In one embodiment, the rate of change of the monitored data at the calibration time (T=0) may be determined using one or more filters including, but not limited to infinite impulse response (IIR) filter, finite impulse response (FIR) filter, backward and/or forward smoothing techniques (e.g., Kalman filtering technique), or any other equivalent one or more causal filters that balance signal noise reduction with lag correction. 
         [0054]    Upon determining the rate of change of the monitored data at the calibration time (T=0), the monitored data at the calibration time (T=0) is updated. In one embodiment, the updated monitored sensor data may include lag corrected monitored data at the calibration time (T=0). Optionally, the lag correction for the monitored data at the calibration time (T=0) may be skipped and not performed. In one embodiment, the lag corrected monitored data at the calibration time (T=0) may be determined by applying the determined rate of change of the monitored data at the calibration time (T=0) to a predetermined constant value. In one embodiment, the predetermined constant value may include, a predetermined time constant. 
         [0055]    For example, in one embodiment, the predetermined time constant may include a fixed time constant in the range of approximately four to fifteen minutes, and which may be associated with the one or more of the patient physiological profile, one or more attributes associated with the monitoring system  100  (including, for example but not limited to, the characteristics of the analyte sensor  101 ). In a further aspect, the predetermined time constant may vary based on one or more factors including, for example, but not limited to the timing and amount of food intake by the patient, exogenous insulin intake, physical activities by the patient such as exercise, or any other factors that may affect the time constant, and which may be empirically determined. 
         [0056]    Referring again to  FIG. 5 , the calibration parameter (for example, the sensitivity of the analyte sensor  101   FIG. 1 ), may be determined for example, in one embodiment, by determining the ratio of the monitored data (optionally lag corrected) at the calibration time (T=0) and the reference data obtained using, for example, the blood glucose meter as described above. In one embodiment, the calibration parameter may be determined by dividing the monitored data at the calibration time (T=0) by the reference data such as the capillary blood glucose value at the calibration time (T=0). 
         [0057]    Thereafter, in one embodiment, the calibrated and updated monitored sensor data at the calibration time (T=0) is determined based upon the monitored data (optionally lag corrected) and the calibration parameter as determined above. For example, in one embodiment, the calibrated and updated monitored sensor data at the calibration time (T=0) may be determined by dividing the lag corrected monitored data at calibration time (T=0) by the determined calibration parameter. 
         [0058]      FIG. 6  is a flowchart illustrating the lag correction and dynamically updating calibration routine of the overall dynamically updating calibration shown in  FIG. 4  in accordance with one embodiment of the present invention. Referring to  FIGS. 4 and 6 , with the counter incremented by one (see step  430  of  FIG. 4 ), the analyte value at the subsequent incremented time (T=1) is retrieved from, for example, the processing and storage unit  307  ( FIG. 3 ) of the receiver unit  104 . In particular, in one embodiment, the rate of change of the monitored data at the calibration time (T=0) is updated based on the monitored data value at the subsequent incremented time (T=1). In other words, with the monitored data values at calibration time (T=0) and prior data and at the subsequent incremented time (T=1), the rate of change of the monitored data at the calibration time (T=0) may be estimated with an improved accuracy. Again, in one embodiment, the rate of change may be determined based on one or more not limited to infinite impulse response (IIR) filter, finite impulse response (FIR) filter, backward and/or forward smoothing techniques (e.g., Kalman filtering technique), or any other equivalent filtering or smoothing techniques. 
         [0059]    With the updated rate of change at the calibration time (T=0) determined, monitored data (optionally lag corrected) at calibration time (T=0) is updated. That is, in one embodiment, the lag corrected sensor data at the calibration time (T=0) is updated based on the prior lag corrected and calibrated data at calibration time (T=0), and in conjunction with the predetermined constant (for example, the predetermined time constant discussed above), and the updated rate of change of the monitored data at the calibration time (T=0). For example, in one embodiment, the lag corrected monitored data at the calibration time (T=0) is updated or determined by taking the sum of the lag corrected and calibration sensor value at calibration time (T=0) as determined above, with the updated rate of change of monitored data at calibration time (T=0) multiplied by the predetermined constant. In other words, in one embodiment, the updated rate of change of the monitored data at calibration time (T=0) may be multiplied by the predetermined constant, and thereafter, the resulting value is added to the lag corrected and calibrated monitored data at the calibration time (T=0) previously determined (see for example, step  420 ). 
         [0060]    Referring again to  FIG. 6 , after determining the updated lag corrected monitored data at calibration time (T=0) based on monitored data at the subsequent incremented time (T=1) as described above, in one embodiment, the calibration parameter (for example, the sensitivity of the sensor  101  ( FIG. 1 ) is updated based on the updated lag corrected monitored data at calibration time (T=0) described above. In particular, in one embodiment, the calibration parameter may be updated by determining the ratio of the updated lag corrected monitored data at calibration time (T=0) and the reference value (for example, the capillary blood glucose value) determined at calibration time (T=0). 
         [0061]    After updating the calibration parameter as described above, in one embodiment, the lag corrected and calibrated monitored data at the subsequent incremented time (T=1) is determined based on the updated calibration parameter value. For example, in one embodiment, the monitored sensor data at the subsequent incremented time (T=1) in one embodiment may be divided by the updated sensitivity to determine the dynamically lag corrected and calibrated monitored sensor data at the subsequent incremented time (T=1). 
         [0062]    In another embodiment, the dynamically lag corrected and calibrated monitored sensor data at the subsequent incremented time (T=1) may be determined based on the updated calibration parameter and the dynamically lag corrected monitored sensor data at the subsequent incremented time (T=1). In this case, the dynamically updated sensor data at the subsequent incremented time (T=1) in one embodiment may be determined by calculating the rate of change of the monitored data at the subsequent incremented time (T=1) using similar filtering techniques as described above, and applying the predetermined constant (for example, the predetermined time constant discussed above), the result of which is then added to the detected or monitored data at the subsequent incremented time (T=1). In other words, in one embodiment, the calculated rate of change of the monitored data at the subsequent incremented time (T=1) is multiplied by the predetermined time constant, and the resulting value is added to the monitored data value at the subsequent incremented time (T=1). This sum in one embodiment represents the dynamically updated monitored sensor data at the subsequent incremented time (T=1). 
         [0063]    In this manner, in one embodiment, lag correction of analyte sensor data may be pseudo-retrospectively (or substantially in real time) updated using the monitored analyte data stream substantially continuously detected by the sensor  101  ( FIG. 1 ) with the dynamic updating of the calibration parameter. Thus, in one aspect, lag error or error due to lag compensation may be overcome by, for example, updating the sensor sensitivity retrospectively with each value of the detected or monitored analyte levels. Accordingly, in one embodiment, calibration inaccuracies due to change (for example, rapid acceleration) of analyte levels after performing discrete calibration may be mitigated by updating the calibration routine taking into consideration the near immediate post calibration analyte sensor data to obtain a more reliable and accurate value associated with the rate of change of the monitored analyte levels. In one embodiment, the overall system accuracy of the monitored and detected analyte values may be improved. 
         [0064]      FIG. 7  illustrates an example of the lag corrected and calibrated sensor data in accordance with one embodiment of the present invention. Referring to  FIG. 7 , a comparison illustrating the improvement in calibration in the dynamically updated (for example, pseudo-retrospectively performed) lag correction approach in accordance with one embodiment is shown. Referring to  FIG. 7 , the reference data points (associated with the capillary blood glucose values) are shown as data points associated with legend (A), the no lag corrected monitored sensor data points are associated with legend (B), the lag corrected monitored sensor data points are associated with legend (C), and the dynamically updated monitored sensor data points are associated with legend (D). 
         [0065]    Referring to  FIG. 7 , more specifically, when calibrating during a high rate of change (for example, between the 3 rd  and 4 th  hour in the Figure), and with uncorrected lag effects, an error in the sensitivity estimate is introduced. For the “No Lag Correction” trace (B), when the high rate of change subsides, it can be seen that the estimated glucose value is substantially overestimated compared to the reference values. When real time lag correction is introduced, it can be seen that the “Real Time Lag Correction” trace (C) is much closer to the reference values, but this is still a substantial overestimation, primarily when the glucose rate of change is negative (calibration occurred when the rate of change was positive). With the dynamic or pseudo-retrospective lag correction in accordance with one embodiment, it can be seen that the data values (shown with trace associated with legend (D)) match the reference values more accurately. 
         [0066]      FIG. 8  illustrates a further example of the lag corrected and calibrated sensor data in accordance with one embodiment of the present invention. Referring to  FIG. 8 , it can be seen that calibration occurs when the glucose rate-of-change is close to zero. Moreover, the real time lag correction signal is shown with a large error when the monitored glucose level is fluctuating, contrasted with the trace or curve associated with the pseudo-retrospective lag correction which, as can be seen from  FIG. 8  substantially tracks the reference glucose values (e.g., measured from the capillary blood). Furthermore, it can be seen that in this example, the trace associated with no lag correction is substantially identical to the trace or curve associated with the pseudo-retrospective lag correction. This may result when the monitored analyte level is not changing during calibration, and thus there may be no lag error to correct, and which is factored in the approaches described in accordance with the various embodiments described herein. 
         [0067]    Referring yet again to  FIG. 8 , it can be also seen that in certain cases, the real time lag correction may result in further distortion or more pronounced error factors as compared with the case where no lag correction is performed. Accordingly, in one embodiment, it can be seen from  FIG. 8  that the pseudo-retrospective lag correction in accordance with the dynamically updating the calibration parameter and the monitored sensor data provides further accuracy and compensation of possible additional errors in the monitored sensor data. This can be seen by comparing the portions of the traces shown in  FIG. 8  during the 11 th  and the 12 th  hours, where a rapid change in the monitored glucose values as a function of time adversely impacts the accuracy of the monitored data with real time lag correction (without the pseudo-retrospective lag correction including dynamically updated calibration parameter. 
         [0068]    Referring to the Figures above, in particular embodiments, the pseudo-retrospective lag correction and calibration and updating of monitored sensor data may be performed by one or more processing units of the one or more receiver unit ( 104 ,  105 ) the transmitter unit  102  or the data processing terminal/infusion section  105 . In addition, the one or more of the transmitter unit  102 , the primary receiver unit  104 , secondary receiver unit  105 , or the data processing terminal/infusion section  105  may also incorporate a blood glucose meter functionality, such that, the housing of the respective one or more of the transmitter unit  102 , the primary receiver unit  104 , secondary receiver unit  105 , or the data processing terminal/infusion section  105  may include a test strip port configured to receive a blood sample for determining one or more blood glucose levels of the patient. 
         [0069]    In a further embodiment, the one or more of the transmitter unit  102 , the primary receiver unit  104 , secondary receiver unit  105 , or the data processing terminal/infusion section  105  may be configured to receive the blood glucose value wirelessly over a communication link from, for example, a glucose meter. In still a further embodiment, the user or patient manipulating or using the analyte monitoring system  100  ( FIG. 1 ) may manually input the blood glucose value using, for example, a user interface (for example, a keyboard, keypad, and the like) incorporated in the one or more of the transmitter unit  102 , the primary receiver unit  104 , secondary receiver unit  105 , or the data processing terminal/infusion section  105 . 
         [0070]    A method in accordance with one embodiment of the present invention includes obtaining a reference data point at a first predetermined time, receiving a first data at the first predetermined time, calibrating the first data based on the reference data point, receiving a second data at a second predetermined time, updating the calibrated first data based on the second data, and calibrating the second data. 
         [0071]    The reference data point may include a blood glucose value. 
         [0072]    The first predetermined time may include a calibration time associated with the calibration of one or more of the first data or the second data. 
         [0073]    The first data and the second data may include a respective one of a monitored analyte value. 
         [0074]    In one embodiment, calibrating the first data may include determining a first rate of change of the first data at the first predetermined time, and performing a first lag compensation of the first data based on the first rate of change to generate a first lag compensated first data. In a further embodiment, calibrating the first data may include determining a first calibration parameter associated with the first data based on the reference data point and the first lag compensated first data, and generating a calibrated first data based on the first calibration parameter and the first lag compensated first data. 
         [0075]    Updating the calibrated first data in one embodiment may include determining a second rate of change of the first data at the first predetermined time based on the second data, and performing a second lag compensation of the first data based on the second rate of change of the first data to generate a second lag compensated first data. 
         [0076]    Also, calibrating the second data may include determining a second calibration parameter associated with the first data based on the reference data point and the second lag compensated first data, and generating a calibrated second data based on the second calibration parameter and the second lag compensated first data. 
         [0077]    A method in accordance with another embodiment may include determining a calibration parameter associated with a detected analyte value, calibrating the analyte value based on the calibration parameter, and dynamically updating the calibration parameter. 
         [0078]    The method in another aspect may include calibrating a second detected analyte value based on the dynamically updated calibration parameter. 
         [0079]    Further, dynamically updating the calibration parameter may also include determining a rate of change of the detected analyte value, and generating a lag compensated analyte value based on the rate of change. 
         [0080]    In addition, calibrating the analyte value may further include determining a sensitivity associated with the detected analyte value, and applying the sensitivity to the lag compensated analyte value. 
         [0081]    Moreover, in still another embodiment, dynamically updating the calibration parameter may include updating the rate of change of the detected analyte value, and updating the lag compensated analyte value, where updating the rate of change may include determining the rate of change of the detected analyte value between a first predetermined time and a second predetermined time. 
         [0082]    In still another embodiment, calibrating the analyte value may include detecting a calibration data, determining a sensitivity based on the calibration data and the lag compensated analyte value, and generating a lag compensated and calibrated analyte value. 
         [0083]    An apparatus in accordance with another embodiment may include one or more processing units, and a memory for storing instructions which, when executed by the one or more processors, causes the one or more processing units to obtain a reference data point at a first predetermined time, receive a first data at the first predetermined time, calibrate the first data based on the reference data point; receive a second data at a second predetermined time; update the calibrated first data based on the second data; and calibrate the second data. 
         [0084]    The memory in another aspect may be configured for storing instructions which, when executed by the one or more processing units, causes the one or more processing units to determine a first rate of change of the first data at the first predetermined time, and to perform a first lag compensation of the first data based on the first rate of change to generate a first lag compensated first data. 
         [0085]    Moreover, the memory in yet another embodiment may be further configured for storing instructions which, when executed by the one or more processing units, causes the one or more processing units to determine a first calibration parameter associated with the first data based on the reference data point and the first lag compensated first data and to generate a calibrated first data based on the first calibration parameter and the first lag compensated first data. 
         [0086]    Additionally, the memory may still be further configured for storing instructions which, when executed by the one or more processing units, causes the one or more processing units to determine a second rate of change of the first data at the first predetermined time based on the second data, and to perform a second lag compensation of the first data based on the second rate of change of the first data to generate a second lag compensated first data. 
         [0087]    In yet still another aspect, the memory may be further configured for storing instructions which, when executed by the one or more processing units, causes the one or more processing units to determine a second calibration parameter associated with the first data based on the reference data point and the second lag compensated first data, and to generate a calibrated second data based on the second calibration parameter and the second lag compensated first data. 
         [0088]    A method in accordance with still another embodiment of the present invention includes, dynamically, and in particular embodiments, in real-time, obtaining reference data at a first predetermined time, receiving measured data prior to and including (or near) the first predetermined time, calculating a first calibration parameter (or parameters) using the data, calibrating the measured data based on the calibration parameter, receiving measured data at a second predetermined time, updating the calibration parameter based on all of the previous data and the newly received measured data, calibrating the newly received measured data based on the updated calibration parameter, and repeating a number of time the process of receiving new measurement data, updating the calibration parameter, calibrating the newly received measurement data, and calibrating any newly received measurement data with the fully updated calibration parameter. 
         [0089]    A method in a further embodiment includes performing lag compensation on the measured data that is used to update the calibration parameter. Lag compensation may optionally be performed on the measured data that is calibrated. A method in a further embodiment includes filtering the measured data that is used to update the calibration parameter. 
         [0090]    An apparatus in accordance with yet still another embodiment includes one or more processing units, and a memory for storing instructions which, when executed by the one or more processors, causes the one or more processing units to dynamically, and in particular embodiments, in real-time, obtain reference data at a first predetermined time, retrieve measured data prior to and including (or near) the first predetermined time, calculate a first calibration parameter (or parameters) using the data, calibrate the measured data based on the calibration parameter, retrieve measured data at a second predetermined time, update the calibration parameter based on all of the previous data and the newly received measured data, calibrate the newly received measured data based on the updated calibration parameter, and repeat a number of time the process of receiving new measurement data, updating the calibration parameter, calibrating the newly received measurement data, and calibrating any newly received measurement data with the fully updated calibration parameter. 
         [0091]    Various other modifications and alterations in the structure and method of operation of this invention will be apparent to those skilled in the art without departing from the scope and spirit of the invention. Although the invention has been described in connection with specific preferred embodiments, it should be understood that the invention as claimed should not be unduly limited to such specific embodiments. It is intended that the following claims define the scope of the present invention and that structures and methods within the scope of these claims and their equivalents be covered thereby.