Patent Abstract:
The present invention provides systems and methods for measuring an analyte in a medium without exposing the medium to contamination. The systems and methods employ a novel combination of a small sensor device embedded in a Luer cap and capable of wirelessly transmitting data to a reading device.

Full Description:
This application claims the benefit of U.S. Provisional Patent Application No. 61/098,479 filed on Sep. 19, 2008, the entire disclosure of which is incorporated herein by reference. 
    
    
     BACKGROUND 
     1. Field of the Invention 
     The present invention relates generally to devices, systems, and methods for measuring the presence of an analyte in a medium and, more specifically, to an optical sensing apparatus and housing permitting continuous exposure to the desired medium. 
     2. Description of the Related Art 
     Sensors for Medicine and Science, Inc. (SMSI) has developed a number of very small wireless sensors for monitoring various analytes (e.g., glucose, CO 2 , O 2 , etc.) present in a body or other medium. In certain embodiments, these very small sensors are adapted to be implanted into a human or animal to measure the presence, absence, or quantity of an analyte in the blood, wherein the sensor itself detects and measures an analyte within its immediate surroundings. The wireless sensors are described more fully in, for example, U.S. Pat. Nos. 5,517,313, 6,330,464, 6,400,974, 7,135,342, and 6,940,590, which are incorporated herein by reference in their entirety. 
     In certain embodiments, these very small implantable sensors are powered by induction from a primary coil contained within an external reader that is configured, for example, as a wristwatch, pager or other devices, and a secondary coil printed on the circuit substrate within the sensor itself. In certain embodiments, the sensor receives power, and transmits its data, via this primary and secondary coil electromagnetic link. See, for example, U.S. Pat. No. 6,400,974, which is incorporated herein by reference in its entirety. 
     Although one design application is human or animal implant monitoring, there is a need for new and improved wireless sensors and methods for using wireless sensors in a range of other applications to provide continuous measurement of an analyte in a medium. 
     SUMMARY 
     The present invention encompasses a sensing apparatus, systems and methods for permitting continuous exposure of an optical sensor to a desired medium for the purpose of measuring the presence of an analyte in the medium. 
     According to an embodiment of the present invention, a sensing apparatus is provided. The sensing apparatus includes a housing that has an external sleeve and a mating member housed within the external sleeve. An optical-based sensor capable of measuring the presence or intensity of an analyte in an analyte containing medium is disposed within the mating member of the housing. The sensor includes a body, internal circuitry, and an internal coil housed within its body. In some embodiments, the internal coil is configured to wirelessly receive electrical power from an external power supply. The sensing apparatus can also include drive circuitry configured to communicate power to and data from the sensor. According to some embodiments, the drive circuitry can be configured to communicate data to the sensor as well. The mating member is configured to mate with a device that is in contact with the medium containing the analyte to be measured such that the optical based sensor is capable of contacting the analyte containing medium. 
     According to another aspect of the present invention, a sensor system is provided. The sensor system includes a plurality of optical-based sensor for measuring the presence of an analyte in an analyte containing medium. Each of the sensors can be disposed in a housing having an external sleeve and a mating member housed within the external sleeve. The sensors can include a body, internal circuitry, and an internal coil housing within the body. The internal coil can be configured to receive electrical power from an external power supply and to transmit data. 
     The system, according to some embodiments of the present invention, may include at least one reading device. The reading device can be coupled to a primary coil, which is configured to transmit power to and receive data from the internal coil of the optical-based sensors. According to various embodiments of the present invention, the reading device may also be configured to transmit data to the optical-based sensors. 
     The system, according to some embodiments of the present invention, may also include a processing device configured to interface with the reading device in order to receive data from at least one of the sensors. Additionally, the processing device may send data to one of the sensors via the reading device according to various embodiments of the present invention. The mating member of the housing can be configured to mate with a device that is in contact with the medium containing the analyte to be measured such that the optical-based sensors are brought into contact with the analyte containing medium. 
     According to another aspect of the present invention, a method of measuring the presence and concentration of an analyte in a medium is provided. The method includes providing a sensing apparatus comprising a housing having an external sleeve and a mating member disposed within the external sleeve. The sensing apparatus can further comprise an optical-based sensor disposed within the mating member of the housing. The optical-based sensor can include a body, internal circuitry, and an internal coil housing within the body. The internal coil can be configured to receive electrical power from an external power supply. The method can further include mating the sensing apparatus with a device that is configured to be in fluid communication with the medium containing the analyte to be measured and exciting the internal coil by electromagnetic induction using a reading device. The method can also include the steps of receiving at the reading device data from the optical-based sensor relating to the presence of an analyte in a medium and transmitting the data to a processing device. The method may can also include the step of sending data to the sensor, according to some embodiments of the invention. 
     According to another aspect of the present invention, a sensing apparatus is provided which includes a housing having a cavity disposed in an outside surface of the housing. An optical-based sensor capable of measuring the presence of an analyte in an analyte containing medium can be disposed within the housing. The sensor can include a body, internal circuitry, and an internal coil housed within its body. The internal coil can be configured to receive electrical power from an external power supply. Drive circuitry can be configured to communicate power to and receive data from the sensor. The drive circuitry may also be configured to transmit data to the sensor according to some embodiments of the invention. The housing can be configured to connect with a device in contact with the medium containing the analyte to be measured such that the optical-based sensor is capable of contacting the analyte containing medium. 
     According to some embodiments of the invention, the sensor may further comprise a light source for introducing light into a fluorescent indicator that interacts with the medium. A photodetector can also be included within the sensor in order to detect light emitted by the fluorescent indicator in response to the introduced light. The photodetector can output a signal proportional to the detected light. The light emitted by the fluorescent indicator can vary in accordance with the presence and concentration of an analyte in the medium. 
     According to some embodiments of the invention, the drive circuitry may be further configured to communicate data from the sensor to an external processing device. This data can include the signal output from the photodetector according to some embodiments. Additionally, the drive circuitry may be configured to communicate data from the processing device to the sensor. According to various embodiments, the communication between the processing device and the drive circuitry may be wireless or the result of a physical connection (e.g., USB, serial cable, coaxial cable, transmission line, etc.) between the processing device and the drive circuitry. 
     According to some embodiments of the present invention, the primary coil can be printed on a PCB substrate and mounted within coupling distance of the internal coil. Additionally, according to some embodiments, the housing may be a luer fitting such as, for instance, a luer lock. The luer fitting can have a six percent taper according to some embodiments of the present invention, however, according to other embodiments the taper is different from six percent. The luer fitting can be configured to mate with devices in fluid or gaseous communication with a medium containing the analyte to be measured. 
     According to some embodiments of the present invention the analyte is glucose. According to various other embodiments, however, the analyte may be CO 2 , O 2 , NaCl, or biomarkers. According to various other embodiments, the sensor may also detect color, refraction index, pH, affinity recognite elements (such as antibodies), ion exchange, and covalent bonding. Additionally, the sensor can be configured to measure more than one analyte. 
     According to some embodiments of the present invention, the mating member is configured to mate with a syringe, or line carrying a fluid or gas. The mating member may also be configured to mate with containers, catheters, or tanks. 
     Further applications and advantages of various aspects and embodiments of the present invention are discussed below with reference to the drawing figures. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  illustrates a sensor assembly according an embodiment of the present invention. 
         FIG. 2  illustrates a functional diagram of an optical-based sensor according to embodiments of the present invention. 
         FIG. 3  illustrates a functional representation of a sensor system according to embodiments of the present invention. 
         FIG. 4  illustrates a flow chart for measuring the presence of an analyte in a medium according to embodiments of the present invention. 
         FIG. 5  illustrates a flow chart for measuring the presence of an analyte in a medium according to embodiments of the present invention. 
         FIG. 6  illustrates a functional representation of a sensor system according to embodiments of the present invention. 
         FIGS. 7(   a )-( c ) illustrate a housing according to embodiments of the present invention. 
         FIG. 8  illustrates a sensor system according to embodiments of the present invention. 
         FIG. 9  illustrates a sensor system according to embodiments of the present invention. 
     
    
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS 
     While the present invention may be embodied in many different forms, a number of illustrative embodiments are described herein with the understanding that the present disclosure is to be considered as providing examples of the principles of the invention and such examples are not intended to limit the invention to preferred embodiments described herein and/or illustrated herein. 
       FIG. 1  illustrates an exploded view of a sensing apparatus  100  according to embodiments of the present invention. The apparatus  100  can include a sensor assembly  102  that itself includes a housing  114  having an external sleeve  104  and a mating member  106  disposed within the external sleeve  104 . In one embodiment, an optical sensor  108  can be disposed within the mating member  106  of the housing. A primary coil  116  can be mounted on a PCB substrate  112 . Drive circuitry  110  can be coupled to the primary coil  112  in order to drive the circuit. Communications cable  118  can connect the drive circuitry to an external processing device. Housing cap  120  may be integrated with housing  114  or separate, as shown in  FIG. 1 . The primary coil  116  and drive circuitry  110  are preferably enclosed within the housing  114  and housing cap  120 . According to some embodiments of the present invention, the sensor can be embedded into the inside of the housing a frictional fit. However, according to other embodiments, the sensor could be embedded within the housing an adhesive such as, for example, a silicone adhesive. 
     According to embodiments of the present invention, communications cable  118  can be replaced with an RF antenna or other means of wireless communication. According to other embodiments, the housing may be a standardized leak-free fitting such as, for example, a luer lock. 
       FIG. 2  illustrates an optical-based sensor  108  according to embodiments of the present invention. In one embodiment, the sensor includes an encasement  202  forming a sensor body. According to some embodiments of the invention, the encasement  202  can function as an optical waveguide. Internal circuitry  204  is mounted on a substrate  228  and can include one or more photodiodes  214   a  and  214   b , a light emitting diode (LED)  208 , an encoder  218 , and a wireless interface. According to some embodiments, photodetectors  214   a  and  214   b  are photodiodes. Filters  216   a  and  216   b  can be placed over photodiodes  214   a  and  214   b.    
     In some embodiments, primary coil  224 , which can be connected to the drive circuitry though connection  226 , can be disposed within coupling distance of internal coil  206  in sensor  108 . This enables the primary coil to transfer power to the internal coil  206  thorough electromagnetic induction. Once powered, the sensor can be configured to excite fluorescent indicator molecules  210  with excitation radiation  222  emitted by LED  208 . Indicator molecules  210  react to the presence of an analyte  212  (e.g., glucose) in the medium surrounding the sensor  108  and, when excited by radiation  222 , emit response radiation  220   a  and  220   b  (such as, for example, fluorescent radiation), which can be detected by the photodetectors  214   a  and  214   b . The amount of response radiation  220   a  and  220   b  emitted varies as a function of the concentration of the analyte present in the medium. Filters  216   a  and  216   b  can be configured to block substantially all light in the spectrum of the excitation radiation  222  while allowing substantially all of the light in the spectrum of the response radiation  220   a  and  220   b  to pass. 
     The photodetectors  214   a  and  214   b  can produce an analog signal which, according to some embodiments, can be encoded as an amplitude modulated (AM) or frequency modulated (FM) signal by encoder  218 . According to some embodiments of the invention, the encoder may also digitally encode the analog output from the photodetectors. The signal output by the encoder  218  can then be transferred to the internal coil  206 , which, in turn, transfers the signal to the primary coil  224  through electromagnetic induction. According to some embodiments of the present invention, the primary coil  224  can be incorporated into a wristwatch. At any rate, the primary coil is oriented coaxially to the internal coil  224  in order to establish electromagnetic coupling according to embodiments of the present invention. According to other embodiments of the present invention, primary coil  224  can be placed immediately adjacent to the backside of housing  114 , but within coupling distance of internal coil  206 . In certain embodiments, the sensor receives power, and transmits its data, via the primary and secondary coil electromagnetic link as described in U.S. Pat. No. 6,400,974, which is incorporated herein by reference in its entirety. 
     Additional examples of the structure and operation of sensors  108  is are described in U.S. Pat. Nos. 5,517,313, 6,330,464, 6,400,974, 7,135,342, and 6,940,590, which are incorporated herein by reference in their entirety. For instance, U.S. Pat. Nos. 5,517,313, 6,330,464, 6,400,974, 7,135,342, and 6,940,590 describe the operation of a sensor capable of detecting the presence of an analyte using indicator molecules. Similarly, U.S. Pat. Nos. 6,330,464 and 6,400,974 describe the operation of the wireless powering and communications facility of a sensor. 
     While the sensor  108  illustrated in  FIG. 2  depicts two photodetectors, any number of photodetectors could be used to allow the sensor to detect a number of different analytes. By increasing the number of photodetectors and altering the chemistry of the indicator molecules (for instance, by including multiple indicator molecules each of which responds to a different analyte), multiple analytes could be detected by a single sensor. According to some embodiments, each photodetector could have a different filter to accommodate a different wavelength of light emitted by different fluorescent indicator molecule  210 , each of which can be configured to fluoresce at a different wavelength. 
     In accordance with other aspects, sensors for gaseous applications can also be configured. For example, an oxygen indicator such as ruthenium biphenylphenanthroline or others could be configured into the sensor and the sensor assembly  102  would become an oxygen sensor—either for dissolved oxygen in a fluid line or in a gaseous line. Indeed, according to various embodiments of the present invention, the sensor assembly  102  could be configured to measure any blood or bodily fluid borne biomarker. Additionally, the sensor, according to some embodiments, could be designed to measure the color, refraction index, salinity, pH, affinity regonite elements such as antibodies, ion exchange, or covalent bonding 
       FIG. 3  illustrates a functional representation of a sensor system according to embodiments of the present invention. The mounted sensor  302  can be mounted within a sterile or luer cap barrier  318 . A wireless interface  304  (which can include a transmitter, a demodulator, and the primary coil) can be placed within coupling distance of the internal coil  206  of sensor  302  and used to wirelessly excite the sensor  302  and receive sensor data from the sensor  302 . In one embodiment of the present invention, the wireless interface  304  can be mounted on the back of sterile or luer cap barrier  318  and provide power to and communication with the sensor through the primary coil. The sensor can be energized by a power amplifier (contained, for example, in drive circuitry) and the primary coil  116 . The wireless interface may contain a demodulator (e.g., AM or FM demodulator) that re-encodes the frequencies from the sensor into a digital pulse stream. The wireless interface  304  can then transmit a signal to a processing device  308 . According to some embodiments of the present invention, the wireless interface transmits the signal  312  to the processing device  308  though an intermediary device  306  such as, for example, a USB dongle. The USB dongle can be programmed to send signals that drive the power amplifier, perform signal processing on receiving signals, and then interface with the processing device  308  through serial, USB communication, or wireless communication. In some embodiments, the intermediary device  306  communicates information  314  to the wireless interface  304  for the purposes of, e.g., transmitter timing. 
     In other embodiments, the intermediary device  306  could also be a wireless communications device, network communications device, or any other suitable means for conveying the signal to the processing device. Additionally, according to other embodiments of the invention, the sensor system does not utilize intermediary device  306 , but wireless interface  304  transmits the signal directly to the processing device  308  via a direct connection. 
     Wireless interface  304  may form part of a reading device, according to embodiments of the invention. Each reading device can be associated with a single sensor. However, one advantage of the present application is that many sensors can be installed at multiple points within a processing line such as a soft drink or beverage plant for quality monitoring. According to the present invention, a single reading device can be multiplexed into a host computer in order to read many sensors at preset intervals for master control or monitoring system. Additionally, for applications requiring infrequent sampling intervals, the reading device may be a hand-held device capable of being carried around periodically, according to some embodiments of the present invention. 
     While  FIG. 1  illustrates the drive circuitry  110  and the primary coil  116  housed within the circuit housing  114 , in some embodiment, the primary coil and the drive circuitry could be disposed in a separate reading device external to the circuit housing. Such an arrangement is illustrated in  FIG. 6 . 
       FIG. 6  is a functional representation of a sensor system according to embodiments of the present invention. As shown, the sensor assembly  102  is disposed against the side of a medium-containing device  600  such that the optical sensor  108  is in contact with medium  602 . Sensor assembly housing  114  abuts the side  600  such that a substantially leak-proof or airtight seal is formed. 
     In operation, reading device  604  can be placed in close proximity (e.g., within coupling distance) to sensor assembly  102 . Reading device  604  is in wireless communication with optical sensor  108  and can be capable of relaying information to processing device  612  via communications channel  610 . According to some embodiments of the present invention, communications channel  610  is a wireless communications interface. In other embodiments, communications channel  610  could also be any sort of communications channel such as a coaxial cable, serial connection, USB cable, direct connection, or any other suitable means of transmitting data from one place to another. 
     According to some embodiments of the present invention, housing  114  comprises a luer fitting.  FIGS. 7(   a )-( c ) depict a luer fitting according to embodiments of the present invention from different angles. Luer fittings (commonly known as “luer,” “luer taper,” or “luer lock”) are used in a variety of applications. For instance, luer fittings are used in syringes, catheters, blood bags, pumps, fermentation sampling syringes, chromatography fittings, and many other fluid (e.g., liquid or gas) handling circuits and apparatus. Luer fittings of standard dimensioning are used throughout medical, food, and industrial applications as simple and universally compatible means of small line liquid or gas connection. Use of luer fittings as the housing, in certain embodiments of the present invention, allows the sensor assembly to be easily installed to operate within medical and industrial fluid circuits utilizing a universal standard. 
     According to some embodiments, a luer fitting  702  may comprise an external sleeve  706  and a tapered cone  704 . According to some embodiments, the cone can have a standard taper of approximately 6%. In other embodiments, the cone can have a taper of other angles. The luer fitting  702  may also include a luer cap  702   b , which can join with the main body of the luer  702   a . According to embodiments of the present invention, the luer cap may include a via  710  that allows a hardwired connection between primary coil  716 , which has been mounted inside of cap  702   b , and the drive circuitry. Alternatively, both the primary coil  716  and the drive circuitry may be located outside of the cap  702   b . In other embodiments, there is no via in the luer cap and the system utilizes a wireless connection as disclosed herein. 
       FIG. 7(   c ) illustrates one embodiment of the luer fitting  702  in a cut-away perspective. As can be seen, cone  704  and external sleeve  706  form a tapered cavity  708 . According to some embodiments of the present invention, the tapered cavity  708  can be smooth. However, as shown in  FIG. 7(   c ), tapered cavity  708  may also include locking threads  712 , which can form a more secure fitting in some cases. Sensor  108  can be mounted partially within cavity  714 . 
     The sensor assembly can be used to take measurements of an analyte in a number of different ways.  FIG. 4  illustrates a flow chart representing one such representative method. According to method  400 , once the sensor  108  is inserted into its housing  114  at step  404 , the housing can be mated with a device at step  406 . The device preferably contains or is in communication with an analyte-containing medium and the housing  114  is preferably mated with the device such that the sensor  108  is brought into contact with the analyte containing medium. The sensor can be excited with reading device  604  at step  408 . The sensor  108  then takes its measurements of the analyte and sends the information to the reading device, which is received at step  410 . The reading device can then transmit the data to the processing device  612  at step  412 . According to some embodiments, the process  400  can terminate at step  412 . According to other embodiments, however, the reading device  604  is configured to take multiple measurements using the sensor  108  over time at predetermined time intervals. In such an embodiment, the reading device  604  can then wait a predetermined time interval at step  414  before looping back to step  408  to excite the sensor  108  again. 
       FIG. 5  depicts a method of reading multiple sensors using the same reading device  604  according to an embodiment of the present invention. According to the method  500 , a first sensor is excited at step  504 . When data is received by the reading device  604  at step  506 , it is transmitted to the processing device  612  at step  508 . At this point, a determination can be made regarding whether another sensor needs to be read at step  510 . If another sensor does not have to be read, then the process ends at step  514 . If another sensor does have to be read, then the reading device  604  can wait a predetermined time interval at step  512  prior to exciting the next sensor at step  514 . After that, the process is repeated at step  506 . 
     As mentioned previously, there are a number of different applications of the sensor assembly, sensor systems and methods of the present invention. For example, in medicine, syringes, catheters, blood bags, and pumps all contain mediums that need to be monitored for analytes of interest. Additionally, other applications, such as fermentation sampling syringes, chromatography fittings, and many other fluid handling circuits and apparatus all require analyte monitoring. Many of these applications use the standard luer fittings. 
     For example, a syringe&#39;s barrel connects to a needle by means of a luer fitting that is molded into the syringe plunger (frequently male) and into the needle (frequently female). There are commonly available fittings of all kinds made to this luer standard including “Y” and “T” connectors (both male and female), valves, manifolds, columns, reservoirs, etc. Furthermore, luer fittings are used for both fluid and gas circuits. By creating a sensor so tiny as to fit within a luer taper, any medical, laboratory, or industrial application using luer standard fittings can easily install a sensor into their fluid or gas circuit by simply utilizing an inexpensive luer “T” or any luer female fitting interface. 
       FIG. 8  illustrates one use of the sensor assembly  102  according to embodiments of the present invention. In  FIG. 8 , device  812  is a syringe comprising a barrel  806 , an open end  808 , a “T” joint  802 , and a tip  804  having a needle  814 . Open end  808  and tip  804  are designed to join with joint  802 . Similarly, the mating portion  106  of the housing  114  is configured to mate with the bottom portion  810  of joint  802 . According to embodiments of the present invention, the housing  114  is mated with tube portion  802  such that when a fluid flows from barrel  806  to tip  804 , the fluid (or analyte containing medium) comes into contact with sensor  108 . According to some embodiments of the present invention, the open end  808  and tip portion  804  are luer fittings 
       FIG. 9  illustrates a partial cut-away of the sensor assembly  102  inserted into the bottom portion  810  of joint  802  according to embodiments of the present invention. As can be seen, the sensor assembly  102  is configured such that sensor  108  is disposed within analyte-containing medium  902 . 
     While  FIGS. 8 and 9  depict device  812  as a syringe, this is meant to be a non-limiting example merely to illustrate the principles behind the functioning of the present invention. Indeed, a person of ordinary skill in the art would understand that the device that mates with sensor apparatus  102  could be anything capable of holding an analyte-containing medium. For instance, according to some embodiments of the present invention, the device is a fluid line, conduit, tube, or catheter. According to other embodiments, the device could be a vessel or container. 
     Beyond the ability to monitor analytes (e.g., glucose) from in-stream and in real time, there are a host of practical advantages in a sensor configuration using a luer connection. Although the sensor assembly with the luer cap can be configured to operate wired or wirelessly, the wireless embodiment has the great advantage of maintaining a monolithic barrier within a sterile fluid (or gas) line. Via the same passive telemetry and remote power system developed for the implantable system, the sensor embedded in the luer cap requires no penetrations across the barrier for power or signal to pass. See, for example, U.S. Pat. No. 6,400,974, which is incorporated herein by reference in its entirety. 
     In an application requiring continuous monitoring (such as in an intensive care unit), the sensor assembly  102  can always remain in communication with a reading device via an external antenna. This antenna can be dedicated to one sensor according to embodiments of the present invention. 
     Depending on the application, the sensor of the present invention may or may not be disposable after use. For example, in an ICU environment for a patient over days or weeks, the sensor (but not the reader, according to some embodiments) could be disposed to prevent any possible cross contamination. However, for many non-medical applications (e.g., food or beverage manufacturing), it may be appropriate to clean and reuse the sensors  108  many times. 
     One of ordinary skill in the art would understand that sensors that use transduction mechanisms other than fluorescence are possible. For instance, according to some embodiments of the present invention, sensors detect the presence of an analyte by using an appropriate sensor to detect colorimetric, refractive index, turbidity, backscatter, or absorbance. 
     According to other aspects of the present invention, the sensing apparatus can be configured as a stand-alone sensor platform. In this embodiment, the apparatus could be configured to stand alone and have remote, radio frequency, or uplinking telemetry capability to allow distance monitoring. This embodiment is useful for applications such as pipeline, hydroponics, water purification, and pollution monitoring (amongst others). By use of the sensor assembly of the present invention, which uses a standard luer in certain embodiments, the sensor cap can easily be removed and replaced or changed within a line without disrupting fluid flow or system pressure for industrial applications. 
     Thus, a number of preferred embodiments have been fully described above with reference to the drawing figures. Although the invention has been described based upon these preferred embodiments, it would be apparent to those of skill in the art that certain modifications, variations, and alternative constructions could be made to the described embodiments within the spirit and scope of the invention.

Technology Classification (CPC): 6