Abstract:
A generic implantable puck that can be used with a number of biosensor configurations. This generic implantable potentiostat telemetry unit (the puck) can also be part of a system to detect glucose concentrations. An electrochemical system partially implantable into a body for detecting glucose concentrations therein is presented. The system comprises an electrochemical sensor, a transmitting puck including an electric circuit connected to the electrochemical sensor for transmitting a signal indicative of the glucose concentrations in the body. There is at least one receiver for receiving the signal from the transmitting puck and a computer system coupled tlo the at least one receiver for processing the signal for patient diagnosis and treatment.

Description:
RELATED APPLICATIONS 
     This application claims the benefit of provisional application No. 60/109,289 filed on Nov. 20, 1998 which is hereby incorporated by reference in its entirety. 
    
    
     TECHNICAL FIELD 
     This invention relates to an electrochemical system partly implantable into a body for detecting glucose concentrations therein and in a similar fashion, other elements, compounds or analytes. 
     BACKGROUND OF THE INVENTION 
     There is a need for an implantable generic device that can be used with different types of electrochemical sensors to facilitate real time monitoring during sensor development. Such a device would be an integrated potentiostat telemetry transmitting unit allowing researchers to test various biosensor configurations for multiple possible uses. In an effort to regulate their glucose levels, diabetic patients monitor their glycemia by repeatedly obtaining a sample of capillary blood by finger-pricking. Since these tests are frequent, painful and time consuming, diabetic patients resist performing an adequate number of these daily glucose measurements. This low compliance, plus the intrinsically discontinuous nature of the technique, leads to the extensive pathology seen in diabetic patients. Thus, a great deal of research is being directed toward the development of new glucose sensors capable of replacing finger-pricking. Such glucose sensors are ideally implantable in the patient, though pain free, as well as small, light-weight and capable of reliable and continuous operation over extended periods of time. In addition it is desirable that such sensors be a part of a system capable of continuous and real time processing of data from the sensors for diagnosis and patient treatment. It is also desirable that the system be easily adaptable to use with various amperometric glucose sensors without the need for redesigning the system for each new sensor. Such a system should be flexible, reliable, stable and easy to use in a telemetried system. 
     Previous telemetried systems require the development of designs taylored to a specific use and set of requirements. Typical telemetried systems utilize voltage-to-frequency conversion to increase frequency stability during frequency modulation of a carrier signal. This method expends objectionable amounts of power, limiting battery lifetime. The transmitted radio frequency carrier and modulation thereof are continuous battery consuming processes. However, this requires the additional step of demodulation and additional signal shaping circuits in order to recover the data. This requires additional power consumption and increased package size. In addition, data accuracy can be tainted by drift in the transmitter and the receiver components. Typical telemetried systems also required dual battery configurations to provide power, thus adding to size. 
     It is desirable in a telemetried system to convert glucose sensor data to digital values in vivo, in order to avoid conversion and modulation errors. Once in digital format, a radio transmitter can utilize a serial data transmission protocol to a receiver thence directly to a computer for processing. An on-off-keyed(OOK) asynchronous serial binary character data transmission method expends battery power only for the brief duration of each digital “one” bit. It expends zero power for each digital “zero” bit. In addition to the glucose sensor data, an individual sensor identification code, and error preventive codes are included in each transmission, termed a “packet.” These data packets uniquely identify one of any number of sensors and provide a means to verify fidelity of the received data. Stored programs can allow direct conversion to glucose concentrations for immediate readout. 
     Monitoring glucose concentrations in diabetic patients is seen in U.S. Pat. No. 4,633,878 which relates to feedback controlled or “closed-loop” insulin pumps known also as “artificial pancreases”. These devices provide a continuous glucose determination in the diabetic patient. Data is transmitted from a glucose sensor to a microprocessor unit, which controls a pump for insulin, or glucose, infusion in order to maintain blood glucose levels within physiological range. In U.S. Pat. No. 4,703,756 an electrochemical system includes a sensor module suitable for implantation in the body to monitor glucose and oxygen levels therein. In U.S. Pat. No. 5,914,026 an implantable sensor comprising a biocompatable electroconductive case which houses a measuring electrode, a reference electrode, an auxiliary electrode, and an electronic circuit for measuring the response of the measuring electrode where the measuring electrode, reference electrode and auxiliary electrode are not in direct electrical contact with one another is provided. 
     SUMMARY OF THE INVENTION 
     This invention describes a generic implantable puck that can be used with a number of biosensor configurations. This generic implantable potentiostat telemetry unit (the puck) can also be part of a system to detect glucose concentrations. An electrochemical system partially implantable into a body for detecting glucose concentrations therein is presented. The system comprises an electrochemical sensor, a transmitting puck including an electric circuit connected to the electrochemical sensor for transmitting a signal indicative of the glucose concentrations in the body. There is at least one receiver for receiving the signal from the transmitting puck and a computer system coupled to the at least one receiver for processing the signal for patient diagnosis and treatment. 
    
    
     EXPLANATION OF THE DRAWINGS 
     Referring now to the drawings wherein like elements and features are numbered alike in the several figures: 
     FIG. 1 is a schematic representation of the electrochemical system of the present invention as it is generally comprised of an electrochemical sensor, a transmitting puck, at least one receiver and a computer system; 
     FIG. 2 is a schematic representation of the electric circuit of the transmitting puck; 
     FIG. 3 is a first schematic representation of the potentiostat circuit of the transmitting puck; 
     FIG. 4 is a schematic representation of the electric filter circuit of the electric circuit of the transmitting puck; 
     FIG. 5 is a second schematic representation of the potentiostat circuit of the transmitting puck. 
    
    
     DESCRIPTION OF THE PREFERRED EMBODIMENTS 
     A description of the preferred embodiment of the present invention will now be had, by way of exemplification and not limitation, with reference to FIGS. 1,  2 ,  3 ,  4  and  5  of the drawing. FIG. 1 is a schematic representation of the electrochemical system  100  of the present invention as it is generally comprised of an electrochemical sensor  200 , including at least one electrode  202 ,  204 ,  206  connected to a transmitting puck  300 . The electrochemical sensor  200  and the transmitting puck  300  are implantable into a body. The transmitting puck  300  is operative to generate a sensor current, I s , through the electrochemical sensor  200  which is proportional to the glucose concentrations in the body. The transmitting puck  300  thence transmits a serial digital signal, V T , which is based upon the sensor current, I s , and is indicative of the glucose concentrations. The electrochemical system  100  further includes at least one receiver  800  for receiving the signal, V T . The at least one receiver  800  may comprise a portable receiver  800  worn by a patient implanted with the electrochemical sensor  200  and the transmitting puck  300 . Such a portable receiver  800  would contain an onboard microprocessor having the capability of providing a continuous or, if desired, periodic readout of the patients glucose concentration, as well as the ability to retain such information in memory and to warn the patient when glucose concentrations are too high or too low. The at least one receiver  800  may also comprise a larger office version connected to a computer system  1000  for processing the serial digital signal, V T , for patient diagnosis and treatment. 
     Reference will now be had to FIG.  2 . Therein depicted is a schematic representation of the transmitting puck  300  including an electric circuit connected to the electrochemical sensor  200 . The electrochemical sensor  200  includes at least one electrode,  202 ,  204 ,  206 . The first electrode  202  of the at least one electrode is commonly referred to as the auxiliary electrode and provides a driving voltage to the electrochemical sensor  200 . The second electrode  204  is commonly referred to as the reference electrode and allows for compensation of circuit and solution losses. The third electrode  206  is commonly referred to as the working electrode wherein the electrochemical reaction occurs. 
     The electric circuit of the transmitting puck  300  includes a power supply  680  for energizing the elements of the electric circuit. A potentiostat circuit  400  is connected to at the least one electrode  202 ,  204 ,  206  of the electrochemical sensor  200 . The potentiostat circuit  400  is further connected to a first digital-to-analog converter  610 , a second digital-to-analog converter  620 , to a microprocessor  600  and to at least one filter circuit  500 . The first digital-to-analog converter  610  provides an excitation voltage, V i , to the electrochemical sensor  200 . The nature of the excitation voltage, V i , is controlled by the microprocessor  600  through the first digital to analog converter  610  and may, for example, be a constant voltage or a ramped voltage or a sinusoidal voltage or a sawtooth voltage signal. Such cyclic voltammetry allows for the characterization and testing of the electrochemical sensor  200 . The second digital-to-analog converter  620  provides an adjustable reference voltage, V g , to the potentiostat circuit  400  in order to allow for bipolar functioning of the electrochemical sensor  200 . The microprocessor  600  is directly connected to the potentiostat circuit  400  to provide gain adjustment of the potentiostat circuit  400  and also to the at least one filter circuit  500  to provide adjustments of filter characteristics. 
     Continuing in FIG. 2, the potentiostat circuit  400  is operative to generate the sensor current, I s , through the electrochemical sensor  200  and to thence convert I s  into an output voltage, V o , proportional to glucose concentrations. The output voltage, V o , is then passed through the at least one filter circuit  500  for filtering of unwanted signals. A filtered signal, V f , is then converted into digital form by an analog-to-digital converter  640  and thence conveyed to the microprocessor  600 , whereupon a serial data signal, V T , is conveyed to the transmitter  700 . 
     Reference will now be had to FIG.  3 . Therein depicted is a schematic representation of the potentiostat circuit  400  of the transmitting puck  300 . The potentiostat circuit  400  comprises a first operational amplifier  402  having a first output terminal  404  connected to a first electrode  202  of the at least one electrode  202 ,  204 ,  206 . The first operational amplifier  402  also includes a first input terminal  406  connected to a single pole-double throw first switch  414 , and a second input terminal  408 . The first operational amplifier  402  includes a first feedback circuit  410  connected firstly to a selected one electrode of the at least one electrode  202 ,  204 ,  206  and secondly to the second input terminal  408  and a single pole-single throw second switch  416 . The first and second switches  414 ,  416  are thrown simultaneously and controlled by the microprocessor  600  by way of signal path  660 . The first feedback circuit  410  comprises a direct connection between the selected one electrode and the second input terminal  408  and a first resistor  412 , R 1 , between the second input terminal  408  and the second switch  416 . The direct connection between the second input terminal  408  and the selected one electrode may be of one of three configurations as designated by the reference numerals  410   a ,  410   b  and  410   c . In a first configuration  410   a , the first feedback circuit  410  is connected to the auxiliary electrode  202 , thus providing a driving voltage at the auxiliary electrode  202 . In a second configuration  410   b , the first feedback circuit  410  is connected to the reference electrode  204 , thus providing compensation for circuit and solution losses. In a third configuration  410   c , the first feedback circuit  410  is connected to the working electrode  206 . The potentiostat circuit  400  further comprises a second operational amplifier  418  having a third input terminal  420  connected to a third electrode  206  of the at least one electrode  202 ,  204 ,  206 , a fourth input terminal  422  connected to the second digital-to-analog converter  620  of the first at least one signal converter, a second output terminal  424  and a second feedback circuit  426  connected to the second output terminal  424 , the third input terminal  420  and the microprocessor  600 . The second feedback circuit  426  comprises a second resistor, R 2 , which may be a digital resistor controlled by the microprocessor  600 . 
     Continuing in FIG. 3, the potentiostat circuit  400  is connected to the first digital-to-analog converter  610  and a second digital-to-analog converter  620  which are biased by a first reference voltage, V r ,  630 . The first digital-to-analog converter  610  is connected to the microprocessor  600  and operative thereby to accept as input therefrom a digital signal. The first digital-to-analog converter  610  thereby provides as output an analog excitation voltage, V i , at node  612  which may be, for example, a constant voltage or a ramped voltage or a sawtooth voltage or a sinusoidal voltage. The second digital-to-analog converter  620  is connected to the microprocessor  600  and operative thereby to accept as input therefrom a digital signal. The second digital-to-analog converter  620  thereby provides as output a second reference voltage, V g , at the fourth input terminal  422  thus allowing for the bipolar functioning of the electrochemical sensor  200 . 
     The function of the potentiostat circuit  400  may be accomplished in one of several modes, i.e., by the aforementioned selection of the configuration of the first feedback circuit  410  coupled with the simultaneous switching of the first switch  414  and the second switch  416  to a first position, “A” (as shown in FIG.  3 ), or a second position, “B.” As an example, if the first switch  414  and the second switch  416  are in position “A” and the first feedback circuit  410  is connected to the auxiliary electrode  202 , then the potentiostat circuit  400  functions as a two-wire potentiostat. If the first switch  414  and the second switch  416  are in position “A” and the first feedback circuit  410  is connected to the reference electrode  204 , then the potentiostat circuit  400  functions as a three-wire potentiostat. If the first switch  414  and the second switch  416  are in position “B” and the first feedback circuit  410  is connected to the working electrode  206 , then the potentiostat circuit  400  functions as a two-wire galvanostat. It will be appreciated that when functioning as such a two-wire galvanostat the third input terminal  420  is disconnected from the working electrode  206 . 
     Reference will now be had to FIG.  4 . Therein depicted is a generalized schematic representation of the filter circuit  500 . The filter circuit  500  is comprised of a third operational amplifier  502  having a third output terminal  504 , a fifth input terminal  506  and a sixth input terminal  508 . The third operational amplifier  502  further includes a third feedback circuit  510  connected to the third output terminal  504  and the fifth input terminal  506 . The third operational amplifier  502  includes a fourth feedback circuit  510   a . Therein, the sixth input terminal  508  is connected to a third reference voltage  520  by way of a first capacitor  516 . A third resistor  512  and a fourth resistor  514  are connected to the sixth input terminal  508 . The third output terminal  504  is connected to a node point  522  between the third resistor  512  and fourth resistor  514  by way of a second capacitor  518 . Such a filter circuit  500  is a second order filter and its filtering capabilities are established by a judicious selection of the values of the third resistor  512 , fourth resistor  514 , first capacitor  516  and second capacitor  518 . In addition the operative nature of the filter circuit  500  may be enhanced by placing the filter circuit  500  either in series or parallel with the same or like filters. Such filters may also be controlled by the microprocessor  600 . The filter circuit  500  is thus operative to accept as input thereto, the output voltage, V o , of the potentiostat circuit  400  and provide as output therefrom an appropriately filtered signal, V f . The filtered signal, V f , is indicative of the glucose concentrations and is conveyed to a first anaolg-to-digital converter  640  where it is converted into a digital form and thence conveyed to the microprocessor  600  whereupon a serial digital signal, V T , is conveyed to the transmitter  700 . The transmitter  700  then in turn conveys V T  to the aforesaid at least one receiver  800 . 
     Reference will now be had to FIG.  5 . Therein depicted is a schematic representation of an alternate to the potentiostat circuit  400  of FIG. 3 connected to a two electrode electrochemical sensor  200 . The positive terminal of a battery  604  is connected to a third switch  602  and the negative terminal thereof is connected to electrical ground  606 . The power supply  600   f  is thereby operative to energize the first operational amplifier  402  and the second operational amplifier  418  with the supply voltage, +V cc  when the thirdswitch  602  is in the closed position (as shown). A voltage converter  608  supplies −V cc  to the second operational amplifier  418 . It is contemplated that +/−V cc  is approximately +/−3.7 volts. When the thirdswitch  602  is in the open position, the first operational amplifier  402  and second operational amplifier  418 , are deenergized. The first input terminal  408  of the first operational amplifier  402  is an inverting terminal and the second input terminal  406  is a non-inverting terminal. The first feedback circuit  410  is a direct connection between the first output terminal  404  and the first input terminal  408 . A potentiometer  438  comprises a voltage divider  436  connected to a fourth reference voltage  442 , held at a potential of +V rl  volts, and a fifth reference voltage  440 , held at electrical ground. The voltage divider  436  is also connected to the non-inverting terminal  406 . Thus, the first operational amplifier  402  is operative to maintain the first output terminal  404 , and thus the first electrode  202  of the electrochemical sensor  200 , at the substantially constant excitation voltage, V i . In particular, by adjusting the voltage divider  436 , the excitation voltage, V i , may be varied from 0 volts to V rl  volts. Thus, the first operational amplifier  402  acts, for example, in a fashion that is commonly referred to as a voltage follower. It is contemplated that V rl  is approximately +1.2 volts and the potentiometer  436  is adjusted so as to make excitation voltage, V i , approximately +0.7 volts to provide glucose concentration related data. 
     Continuing in FIG. 5, the third input terminal  420  of the second operational amplifier  418  is an inverting terminal and the fourth input terminal  422  is a non-inverting terminal connected to electrical ground  444 . A third switch  446  is a two position switch that connects the second electrode  206  of the electrochemical sensor  200  to the third input terminal  420  and turns the electrochemical sensor  200  On or Off. The voltage at the second electrode  206 , V w , varies with the glucose concentration thus resulting in a voltage drop, ΔV=V i −V w , across the first electrode  202  and the second electrode  206 . The voltage drop, ΔV coupled with the impedance of the glucose, Z g , generate the aforesaid sensor current, I s . The second feedback circuit  426  comprises a capacitor  426   a  in parallel with a resistor  426   b . The resistor  426   b  acts to set the amplifier gain and in conjunction with the capacitor  426   a , acts as a low pass filter in order to dampen high frequency noise. An offset current compensation circuit  428  comprises a variable resistor  428   a  connected to a fourth switch  432  and the sixth reference voltage  430  held at a potential of Vr2 volts. The fourth switch  432  is a two position switch that engages or disengages the offset current compensation circuit  428 . With the fourth switch  432  in the closed position (as shown) and by adjusting the variable resistor  428   a , an offset bias current, I B , is established at third input terminal  420 . Continuing in FIG. 5, a fifth switch  434  is a two position switch that turns an optocoupler  900  On or Off. The second operational amplifier  418  is thereby operative to convert the sensor current, I s +I B , into an output voltage, V o , at the second output terminal  424  and thus acts, for example, in a fashion that is referred to as a transimpedence amplifier. 
     Continuing in FIG. 5, the second operational amplifier  418  is connected to the optocoupler  900  by way of the fifth switch  434 . The optocoupler  900  comprises a first optical device  902 , such as a light emitting diode. The first optical device  902  is optically coupled to a second optical device  904  such as a photocell, a photosensitive resistor or a phototransistor. The cathode of the first optical device  902  is connected to the fifth switch  434  and the anode is connected to electrical ground  906 . As such, when the output voltage, V o , at the second output terminal  424  or the fifth switch  434  is negative, the first optical device  902  emits an optical signal  908  to which the second optical device  904  is responsive. The operative nature of the first optical device  902  is such that the optical signal  908  emitted therefrom is consistent with the output voltage, V o , at the second output terminal  424  when the third switch  434  is closed (as shown). The optocoupler  900  is connected to the microprocessor  600  via the second optical device  904 . However, the nature of the coupling of the first optical device  902  and the second optical device  904  via the optical signal  908  is such as to provide electrical isolation of the microprocessor  600  from the potentiostat circuit  400 . As a result of the aforesaid responsivity of the second optical device  904  to the optical signal  908 , a changing resistance, ΔR, is developed across the second optical device  904 . The output, ΔR, of the second optical device  904  is conveyed to the microprocessor  600  for conversion to a digital serial data signal, V T , which is then conveyed to the transmitter  700 . The transmitter  700  is operative to transmit a digital serial data signal V T , indicative of the changing resistance, ΔR, in the optocoupler  900  to the at least one receiver  800 . V T  is then conveyed to the computer system  1000  for processing thereof by appropriate controlling software, e.g., screen readout and data logging to a storage disk. It is contemplated that the aforesaid transmittal of the serial data signal, V T , is by a radio frequency electromagnetic wave at a carrier frequency of about 303.85 Mhz. In particular, V T  is in the nature of digital counts whereby 1 digital count=10 ΔR ohms. The serial data signal, V T , includes, for example, the transmitter serial number, the resistance value in the number of digital counts and a timing scheme governing data transmission rates, data logging rates and received data error prevention information. V T  is conveyed from the at least one receiver  800  to the computer system  1000  whereat actual glucose concentration values are displayed on a computer screen for immediate readout provided by real time conversion of digital counts based upon earlier calibration, curve fitting and tables. The computer system  1000  is operative to initialize the status of the transmitting puck  300 , deactivate the transmitting puck  300 , error check V T , process V T  for display to a screen, log V T  to a disk file and commands the transmitting puck  300  to set transmission intervals over a range from 5 seconds to 10 minutes. 
     Thus it will be appreciated that the electrochemical system provides real time continuous and reliable data related to the glucose concentrations in a body. The microprocessor  600  controls the status of the potentiostat circuit  400  by controlling the first and second switches  414 ,  416 , controls the bias voltage, V g , the excitation voltage, V i , establishes alarm levels and directs the transmission of V T . The transmitter  700 , including a near field receiver, accepts as input from the microprocessor  600  the serial data value, V T , in a serial data protocol and by digital signal processing converts V T  into a binary stream to be conveyed to the at least one receiver  800 . The at least one receiver  800  accepts as input the binary stream and recovers therefrom the serial data signal, V T , for conveyance to either the computer system  1000  for processing thereof or immediate display to a patient. The at least one receiver  800  includes a near field transmitter operative to initialize the transmitting puck  300  and place the transmitting puck  300  in standby mode. 
     While preferred embodiments have been shown and described, various modifications and substitutions may be made thereto without departing from the true spirit and scope of the invention. Accordingly, it is understood that the present invention has been described by way of illustrations and not limitation.