Abstract:
A system and method are disclosed for utilizing sensors with existing devices. An interface module is used in combination with a newer sensor, such as a fluorescence oxygen sensor, and an older legacy device. The older legacy device supplies a polarizing voltage, and anticipates a measured current of between 0 and 100 nA. The newer sensor requires no polarizing voltage and delivers an output of 0-10 volts in one embodiment, and 4-20 mA in another embodiment. The interface module receives the output from the sensor, and converts it into a useable signal to the legacy device. In another embodiment, the interface module comprises a number of outputs, such that both legacy devices and newer devices can be in communication with the sensor simultaneously. The interface module can be used in conjunction with a reactor chamber or other pharmaceutical process.

Description:
[0001]    This application claims priority of U.S. Provisional Patent Application No. 61/169,415, filed Apr. 15, 2009, the disclosure of which is incorporated herein by reference in its entirety. 
     
    
     BACKGROUND OF THE INVENTION 
       [0002]    Many industries, such as the pharmaceutical industry, employ sensing devices to monitor the progress or outcome of a particular event. Often, these sensing devices are used to provide input to a controller, which then varies its output, based on this input. The output of the controller is typically used to influence, affect or control the particular event. 
         [0003]    For example, in a bioreaction, it may be important to monitor and control a number of characteristics of the reaction, including but not limited to temperature, pH, oxygen concentration, or other parameters. Because of this, devices have been developed to sensor these characteristics. There exists a plethora of pH sensors, dissolved oxygen sensors and temperature sensors. 
         [0004]    However, while sensing the characteristic is important, it is equally important to be able to monitor and track these characteristics over time. Additionally, it is important to use these characteristics to determine future actions. For example,  FIG. 1  shows a simple example of a closed loop control system which can be used with a bioreactor. In this figure, a temperature sensor  10  may be used to monitor the temperature of a particular reaction occurring within a reaction chamber  20 . Based on the output of the temperature sensor  10 , a controller  30 , in communication with that sensor  10 , may vary the output of a heating element  40 . In this way, if the temperature within the reaction chamber must be within a prescribed temperature range, the controller  30  can use the sensor  10  and the heating element  40 , in conjunction with a software control loop, to insure that these conditions are met. 
         [0005]    Additionally, the sensor  10  may be in communication with other devices. For example, the output of a pH sensor may be in communication with controller, a logging device and/or data storage device. The attached device samples the output of the specific sensor over time. This sampling step may be performed periodically, such as at fixed time intervals. In other embodiments, this sampling step is performed at sporadic intervals, or based on other external events. 
         [0006]    In the case of a data logger, the value sampled is simply stored, usually with an associated timestamp, so that a graph of that characteristic over a period of time can be generated. In the case of the controller, the value is sampled so that corrective action can be performed. For example, as described above, in the case of a temperature sensor, the controller may be in communication with a heating element, such that if the temperature reading is below a predetermined threshold, the controller actuates the heating element. Similar actions can be taken in response to pH or dissolved oxygen readings. 
         [0007]    One of the most common dissolved oxygen sensor is known as a polarographic sensor. A representative sensor is shown in  FIG. 2 . The sensor  100  includes a membrane  120  through which oxygen can pass. It also includes a cathode  130  and an anode  160 . In some embodiments, the cathode  130  is made from a conductive material, such as platinum. In some embodiments, the anode  160  is made from a conductive material, such as gold or silver. These two conductive components are separated by an insulator  140 , such as glass. An external device provides a voltage potential, such as between 600 and 800 mV, between the cathode  130  and the anode  160 . 
         [0008]    In operation, oxygen molecules diffuse through the membrane  120 . These molecules are reduced at the surface of the cathode  130 , such as according to the following equation: 
         [0000]      O 2 +2H 2 O+4 e   − →4OH −   
         [0000]    At the anode, an oxidation reaction is occurring, thereby producing electrons. These electrons move toward the cathode  130 , thereby generating a current proportional to the oxygen concentration. This current can then be measured by a device, such as a controller or a logging device. 
         [0009]    Because of the popularity of polarographic sensors, many devices, such as controllers, including those made by Applikon, were designed to interface directly to them. In other words, these devices, provided a polarizing voltage of 600-800 mV, and were designed to measure the resulting current flow, which is in the range of 0-100 nA. These devices also were used to control operations, such as bioreactions, and have been used for a significant amount of time. Thus, there exists a large installed base of these controllers and other devices, configured to interoperate with polarographic sensors. 
         [0010]    More recently, alternative sensors have been developed. Unlike traditional polarographic sensors, these alternative sensors typically use a different indicator of oxygen content. One such indicator is fluorescence. In one embodiment, the sensor has an emitter, which emits light, typically at a specific wavelength, such as 475 nm. The light is directed toward a sensing element. The sensing element has a thin layer of hydrophobic material. A compound capable to fluorescing, such as ruthenium, is trapped within the hydrophobic material, effectively shielded from the water. The light excites the ruthenium, which then emits energy at a specific wavelength, such as 600 nm. 
         [0011]    Oxygen is able to effectively quench the fluorescence of ruthenium. Collision of an oxygen molecule with a fluorophore in its excited state leads to a non-radiative transfer of energy. Thus, the more collisions that occur, the less fluorescence is created. The frequency of collisions is directly related to the concentration of oxygen molecules. Therefore, the measured fluorescence is a direct measure of the concentration of oxygen molecules. 
         [0012]    These sensors are typically more accurate than traditional polarographic sensors. Furthermore, since they do not include any precious metals, such as platinum and silver, they are typically much less expensive. These qualities make these newer sensors the preferred choice in many applications. For example, disposable systems are more likely to utilize fluorescence oxygen sensors, due to the lower cost (especially when taking into account that the sensor will be discarded with the bag). 
         [0013]    However, today, it is not possible to use these new sensors with existing systems. Unlike polarographic sensors, this optical-based sensors do not require a polarizing voltage input. Furthermore, rather than producing a very small current, the output of an optical-based oxygen sensor is typically between 0 and 10 volts. In another embodiment, the output is typically between 4 and 20 mA. These outputs are completely incompatible with the input characteristics of existing devices, such as Applikon controllers. Therefore, the adoption of these new optical-based sensors has been slowed. 
         [0014]    Therefore, it would be beneficial if there were a system and method whereby these new, inexpensive, accurate oxygen sensors can be employed with existing devices, such as data loggers and controllers. Furthermore, it would be advantageous if these sensors were compatible with both older legacy controllers, and newer devices, such that two devices, such as a data logger and a controller, can be used simultaneously. 
       SUMMARY OF THE INVENTION 
       [0015]    The problems of the prior art are alleviated by the system and method disclosed herein. An interface module is used in combination with a newer sensor, such as a fluorescence oxygen sensor, and an older legacy device. The older legacy device supplies a polarizing voltage, and anticipates a measured current of between 0 and 100 nA. The newer sensor requires no polarizing voltage and delivers an output of 0-10 volts in one embodiment, and 4-20 mA in another embodiment. The interface module receives the output from the sensor, and converts it into a useable signal to the legacy device. In another embodiment, the interface module comprises a number of outputs, such that both legacy devices and newer devices can be in communication with the sensor simultaneously. 
     
    
     
       BRIEF DESCRIPTION OF DRAWINGS 
         [0016]      FIG. 1  illustrates a simple control system; 
           [0017]      FIG. 2  is a representative cross section of a polarographic oxygen sensor of the prior art; 
           [0018]      FIG. 3  is a schematic drawing of first embodiment; 
           [0019]      FIG. 4  is a schematic drawing of a second embodiment; 
           [0020]      FIG. 5  is a schematic drawing of a third embodiment; 
           [0021]      FIG. 6  is a schematic drawing of a representative circuit used in the present invention. 
       
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
       [0022]    Pharmaceutical and biological processes often involve the transformation of materials into a final product, wherein the materials undergo various reactions. Often, it is imperative to monitor these reactions, and control them, using parameters such as temperature, pH, oxygen concentration, and others. To do so, sensors are incorporated into the reaction chambers, so that the sensor can obtain and transmit information related to a particular characteristic of the reaction. These reaction chambers can be of any type, including vats and disposable plastic bags. 
         [0023]      FIG. 3  shows a first embodiment of the present invention. As described above, sensors, such as fluorescence oxygen sensors, produce an output that represents a measure of the characteristic that they are sensing. For example, for a fluorescence oxygen sensor, this output may be, in some embodiments, between 0 and 10 volts. In other embodiments, this output is between 4 and 20 mA. However, the specific output range and type is not important; other output ranges are within the scope of the invention. 
         [0024]    Sensor  200  is such a sensor, having an exemplary output of 0 to 10V. This sensor  200  is to be connected to device  210 . As described above, older legacy devices have certain expectations or specifications for the attached sensor. In some embodiments, the device  210  provides a polarization voltage of between 600 and 800 mV between its two leads  211 , 212 . The output of the sensor is expected as a current between the two leads. In some embodiments, this current is between 0 and 100 nA. 
         [0025]    Due to the difference in specifications between the sensor  200  and device  210 , these two components cannot be connected directly together. Therefore, an interface module  220  is placed between the two components. This interface module  220  has an input port  222 , adapted to receive signals conforming to a first specification from the sensor  200 , and has an output port  221 , adapted to generate outputs conforming to a second specification to the device  210 . In one embodiment, the first specification is 0-10 volts. In a second embodiment, the first specification is 4-20 mA. The second specification, in one embodiment, is 0-100 nA between lead  211  and  212 , with a polarizing voltage of 600 to 800 mV. 
         [0026]    The system shown in  FIG. 3  can be used with a fluorescence oxygen sensor, and a legacy controller, such as from Applikon. This system enables a variety of new configurations. In one embodiment, a disposable pharmaceutical system can be used. Such a system may include disposable storage bags, reaction bags and filtering devices. To reduce total product cost, it is advantageous to use fluorescence oxygen sensors, as these are less expensive than traditional polarographic sensors. However, disposable systems, much like traditional systems, need to be monitored and controlled. The inability of an existing legacy controller to operate with a fluorescence sensor thwarts the adoption of this configuration. However, the disclosed system, and specifically the inclusion of the interface module  220 , enables such a disposable configuration. 
         [0027]    In another embodiment, a traditional bioreactor can be fitted with fluorescence oxygen sensors. These sensors require less maintenance, less calibration and are more accurate than polarographic sensors. Therefore, they may be more desirable in reactions requiring precision control. The introduction of the interface module  220  allows a legacy controller  210  to be used with this bioreactor. 
         [0028]      FIG. 4  shows a second embodiment of the present invention. This embodiment includes the sensor  200  and device  210 . However, in this embodiment, a second device  230  is introduced. 
         [0029]    In some embodiments, this second device  230  is adapted to receive signals conforming to the second specification. In other words, it can interface directly to the sensor  200 . In this embodiment, the interface module  240  contains an input port  241 , adapted to receive signals from the sensor  200 . The interface module also includes the circuitry required to convert these signals from the first specification to the second specification for the first device  210 . This modified output is available on port  242 . The interface module  240  also includes a second output port  243  to which the second device  230  can attach. This second output port  243  simply passes the signals received at input port  241  from the sensor  200  to the second device  230 . In some embodiments, the interface module may buffer this signal to reduce noise or load. One exemplary configuration may include a data logger functioning as the second device  230 . This data logger may be able to accept a signal having an output between 0 and 10 V. In such a scenario, it is attached to the second port  243  on the interface module  221 . 
         [0030]    In other embodiments, this second device  230  is also a legacy device, and can only receive signals conforming to the first specification. In this embodiment, the interface module  221  contains duplicate circuitry to produce two identical outputs on output ports  242 ,  243  for the two devices  210 ,  230 . One exemplary configuration may include a legacy data logger, which can only accept inputs from 0-100 nA. 
         [0031]    In yet other embodiments, this second device  230  requires inputs conforming to a third specification. In this scenario, the interface module  240  may include circuit to convert input signals received on input port  241  to output signals of a third specification on output port  243 . 
         [0032]    In a third embodiment, shown in  FIG. 5 , the interface module  260  has a plurality of output ports, where one or more output ports  261   a,b  conform to the first specification, and one or more output ports  262   a,b  conform to the second specification.  FIG. 4  shows two legacy controllers  210   a,b  and two other devices that conform to the second specification  270   a,b . However, the number of each type of device is not limited, and all configurations of devices are within the scope of the invention. 
         [0033]      FIG. 6  shows a schematic of a representative circuit used to convert signals from a first specification to a second specification. In this embodiment, signals received by the interface module are in the range of 0-10 V, and the outputs must be between 0-100 nA (with a 600-800 mV polarizing voltage). 
         [0034]    Referring to the upper portion of the Figure, the power supplies for the circuit are created, using traditional components and circuitry. The power for the interface module can be supplied either by a battery  600  or a remote power supply (not shown). The selection of the power source is performed using traditional methods, such as jumper  601 . In some embodiments, the remote power source is at a voltage greater than required. In such a scenario, a voltage regulator  602  may be used to convert the incoming voltage to a lower level. The interim voltage  603  is used to create the power rails. In some embodiments, a linear regulator  604  is used to create a smooth output voltage  605 . In some embodiments, a switching regulator  606  is used to create a negative rail voltage  607 . Other methods of creating the necessary voltages for the interface module are well known and are within the scope of the disclosure. 
         [0035]    A connector  610  is used to connect the output of the sensor to the interface module. In some embodiments, the output of the sensor is a voltage, in the range from 0-10 volts. In such an embodiment, a resistor divider  611  may used to reduce the voltage such that it is less than the voltage rail  605 . In some embodiments, an op amp  612  is used to buffer the incoming signal so as to minimize the current load thereon. In other embodiments, the output of the sensor may be a current in the range from 4-20 mA, although other ranges are also possible and within the scope of the invention. In such an embodiment, a resistor, or resistor divider network, may be used to convert this current output to a voltage. 
         [0036]    In certain embodiments, a programmable microprocessor, having an analog to digital (A/D) converter, and a pulse width modulated (PWM) output is used. In other embodiments, other forms of D/A conversion can be employed. The microprocessor may also have a storage element for storing code, tables or software to be executed. The microprocessor may also have RAM, which can be rewritten to serve as temporary storage. In the embodiment shown in  FIG. 6 , the buffered input signal  613  is connected to the internal A/D converter of programmable microprocessor  615 . The microprocessor  615  converts this analog voltage to a digital value, representative of the received analog voltage. Once this is completed, the microprocessor then determines a suitable output voltage. This determination can be based on an algorithm, which uses the incoming digital value in an equation to generate the output voltage. Such a method is useful when the output voltage has a linear or nearly linear relationship to the input voltage. In other scenarios, it may be advantageous to use a translation table to determine the appropriate output voltage. In other words, the incoming digital value is used to index a table, which provides the suggested output voltage. 
         [0037]    Alternatively, in lieu of a microprocessor, especially in scenarios where the desired output voltage is proportional or linearly related to the input voltage, a circuit comprising passive and active components, such as resistors, capacitors, and opamps, can be employed. 
         [0038]    Returning to  FIG. 6 , the output voltage produced by the microprocessor may be a PWM signal. In such a case, it may be necessary to convert this signal back to an analog value. In some embodiments, a low pass filter  617  may be used to convert a PWM signal to an analog voltage  618 . An opamp  619  is then used to buffer this analog voltage  618 . In other embodiments, the microprocessor may include a D/A converter and directly output an analog value. 
         [0039]    As described above, in some embodiments, the output specification is 0-100 nA, with a 600-800 mV polarizing voltage. Therefore, the final stage of the circuit must convert an analog voltage, which is indicative of the desired current, into a current in the proper range. In this embodiment, the current is determined by measuring the voltage across resistor  634 , which will be between 0 mV (no current) and the full polarizing voltage of 600-800 mV (maximum current). Opamp  632  simply buffers the voltage across resistor  634 , and a resistor divider  633  may be used to reduce the voltage (if necessary) before it feeds into the negative input of opamp  630 . In some embodiments, a circuit having a gain greater than one is used to amplify the voltage measured across resistor  634  such that the entire voltage range of the opamp  630  can be exploited. Such an embodiment may also increase the precision of the output. 
         [0040]    The positive input of opamp  630  is fed by resistor divider  620 . The output of opamp  630  is used to drive the gate of a FET transistor  631 . This FET  631  has a variable resistance across its other two terminals, where that resistance is determined by the voltage applied to the gate of FET  631 . The greater the voltage applied to the FET, the lower the resistance across its other two terminals. Thus, if the desired voltage, as applied to the positive terminal of opamp  630  is greater than the measured voltage, as applied to the negative terminal of opamp  630 , the output of opamp  630  will increase, thereby lowering the resistance of FET  631 . By reducing the resistance across FET  631 , the current flow through resistor  634  increases. 
         [0041]    As suggested above, other embodiments are also possible, including ones that do not include a microprocessor. 
         [0042]    Furthermore, other variations of the circuit of Figure are possible. For example, if two output ports are desired, where both conform to the second specification, components  630 - 634  can be replicated to create a second output port. If an output port conforming to the first specification is desired, an opamp, configured as a buffer may be added near the input  610 . Furthermore, if an output conforming to a third specification is desired, the applicable parts of the circuit shown in  FIG. 6  can be duplicated. In certain embodiments, it may be necessary to replicate the microprocessor  615 . However, the code executed by the microprocessor, or the lookup tables contained within may be modified. 
         [0043]    While the above description illustrates a pharmaceutical system, the invention is not so limited. Other systems, such as those reactions using enzymes, nutraceuticals and pure chemical systems, can also utilize the present invention. 
         [0044]    The terms and expressions which have been employed herein are used as terms of description and not of limitation, and there is no intention in the use of such terms and expressions of excluding any equivalents of the features shown and described (or portions thereof). It is also recognized that various modifications are possible within the scope of the claims. Other modifications, variations, and alternatives are also possible. Accordingly, the foregoing description is by way of example only and is not intended as limiting.