Abstract:
A biochemical sensor based on ball integrated circuit technology which is designed to be biocompatible for implantation within a human or animal body. A sensor media is mounted to the ball integrated circuit, the sensor media operable for sensing biochemical molecules. An onboard communication link transmits data sensed by the sensor media from the ball integrated circuit.

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application claims priority under 35 U.S.C. 119(e) to U.S. Provisional Patent Application Ser. No. 60/137,071 entitled “GLUCOSE SENSOR” filed Jun. 2, 1999, and is related to the following pending applications: U.S. patent application Ser. No. 09/448,781 entitled “SPHERICALLY-SHAPED BIOMEDICAL IC,” filed Nov. 24, 1999; U.S. patent application Ser. No. 09/448,642 entitled “MINIATURE SPHERICAL-SHAPED SEMICONDUCTOR WITH TRANSDUCER,” filed Nov. 24, 1999; and U.S. patent application Ser. No. 09/521,922 entitled “IMPLANTABLE DRUG DELIVERY SYSTEM,” filed Mar. 9, 2000, each of which is hereby incorporated by reference. 
    
    
     TECHNICAL FIELD OF THE INVENTION 
     This invention is related to the field of biochemical sensors using integrated circuits. The sensors are specifically designed to be biocompatible for implantation in the human or an animal body, but may also be used in laboratory or industrial settings. The sensor communicates to either or both of a pump actuator, and to an externally located RF transmitter/receiver. 
     BACKGROUND OF THE INVENTION 
     Diabetes mellitus is a disease in which glucose levels in the patient&#39;s blood become out of balance and largely unregulated and is the leading cause of morbidity in the United States. Studies have shown that when glucose levels are tightly maintained, induced secondary pathological states such as peripheral vasculopathy, which leads to such conditions as diabetic retinopathy, neuropathy, nephropathy and amputation of extremities, are largely avoided. The level of glucose control required to inhibit these associated pathological states is typically beyond the ability of diabetic patients to regulate in their own homes. Diabetic patients are required to prick a finger multiple times a day, draw a small sample of blood, place it in a glucose sensor, and then administer themselves an appropriate injection of insulin. Patient compliance is clearly an issue. If a patient does not accurately dose their insulin levels to correspond with glucose levels, then this level of insulin therapy is insufficient to stop the progress of the above mentioned pathological conditions. 
     A major step forward in the fight against diabetes would be the ability to automatically monitor blood glucose levels using one or more embedded sensors which eliminate the need for frequent finger pricks. After the glucose levels were automatically sensed, the sensor should be smart enough to determine if the levels were outside a preset range. The sensor would then either send a message to the patient that their glucose levels were out of range, or in the preferred case, activate an implanted insulin pump to automatically maintain glucose levels within physiological levels. 
     The disclosed sensing architecture describes a device, and outlines the fabrication process of the device to make a wireless glucose sensor. Such a sensor is ideal for implantation within the human body for the control of diabetes mellitus. However, it could also be used in biotech processing plants where glucose levels are required to be maintained within a certain range, or in the veterinary market for the treatment of animals that have diabetes. Because this sensor is based on semiconductor technology, the preferred embodiment is to automatically actuate a pump to meter an appropriate dosage of insulin or to add additional glucose if levels rose above or fell below a programmable range. The disclosed sensor architecture specifically deals only with the sensor. The connection of how this sensor may interact with a pump is described in a previously submitted U.S. patent application Ser. No. 09/521,922 by Ishikawa et al., entitled “Implantable Drug Delivery Systems,” filed Mar. 9, 2000, and which is hereby incorporated by reference. The sampling frequency of the glucose sensor is programmable, and is determined by the radio frequency (RF) transmitter/receiver, which is external to the sensor. In the case of implantation in the human body, the external transmitter/receiver is worn by the patient, and is ideally similar in size and appearance to a beeper or other socially acceptable device. In the case that there is no pump available, or if the pump requires maintenance, this external transmitter/receiver can be programmed to sound an audible alarm or series of various alarms. The patient would then be able to manually administer an appropriate dosage. This constant feedback to the patient would allow a much tighter control of blood glucose levels, and could potentially result in a substantial decrease in mortality and morbidity currently associated with diabetes. 
     The disclosed sensor system is valid for a variety of biological molecules. In particular, any biological molecule that undergoes enzymatic oxidation with the concomitant production of an acid and/or hydrogen peroxide can be detected by one or more of the disclosed embodiments as described herein. Detailed discussion focuses on glucose, for example, but it should be kept in mind that glucose is only one specific example of the multitude of applications. 
     SUMMARY OF THE INVENTION 
     The present invention disclosed and claimed herein, in one aspect thereof, comprises a biochemical sensor fabricated on a ball integrated circuit. A sensor media is mounted to the ball integrated circuit, the sensor media operable for sensing biochemical molecules. An onboard communication link transmits data sensed by the sensor media from the ball integrated circuit. 
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS 
     For a more complete understanding of the present invention and the advantages thereof, reference is now made to the following description taken in conjunction with the accompanying Drawings in which: 
     FIG. 1 illustrates a ball semiconductor sensor; 
     FIG. 2 illustrates a pH sensitive hydrogel covalently attached to the surface of a ball semiconductor sensor; 
     FIG. 3 illustrates the enzyme glucose oxidase attached to the hydrogel; 
     FIG. 4 illustrates the ball semiconductor with the attached hydrogel in the presence of glucose; 
     FIG. 5 illustrates the ball semiconductor with the attached hydrogel in the absence of glucose; 
     FIG. 6 illustrates a ball semiconductor sensor that has at least two osmotic pressure sensors located on the same ball sensor; 
     FIG. 7 illustrates two ball sensors in a cluster with electrodes placed at precise locations near the bumps that connect the two ball sensors; 
     FIG. 8 illustrates a graph indicating the volume of the hydrogel as a function of the change in pH; 
     FIG. 9 illustrates a corresponding graph showing the anticipated sensed pressure as a function of pH changes, which will be proportional to graphing pressure changes as a function of glucose concentration if glucose oxidase is attached to the hydrogel; 
     FIG. 10 illustrates a ball semiconductor sensor having a well for electrochemical detection of glucose using a pH sensitive hydrogel coupled with an electrically conductive polymer; 
     FIG. 11 illustrates a block diagram of a ball sensor with an integral transducer in combination with a radio frequency communication system in accordance with the present invention; 
     FIG. 12 illustrates a schematic block diagram of the receiver/transmitter and a detection/power system; 
     FIGS. 13A and 13B illustrate alternative embodiments for the receiver/transmitter and the storage capacitors associated therewith; 
     FIG. 14 illustrates a perspective view of one of the ball sensor semiconductor spheres having antenna leads disposed thereon; 
     FIG. 15 illustrates a cross-sectional diagram of the portion of the surface of the ball sensor spherical IC of FIG. 14; 
     FIG. 16 illustrates a side view of an alternative embodiment utilizing additional circuitry or structure attached to the ball IC for providing a local power source; 
     FIG. 17 illustrates a schematic block diagram of the ball IC using a battery as the local power supply system; 
     FIG. 18 illustrates a side elevation of a cluster of semiconductor balls that may be employed in a sensor function, according to a disclosed embodiment; 
     FIG. 19 illustrates a cross section taken along the line  19 — 19  of FIG. 18 to expose the four contacts between two balls; 
     FIG. 20 illustrates a cluster or aggregation of balls; and 
     FIG. 21 illustrates an embodiment where a ball IC is constructed with a pump that is connected on one end through plumbing to reservoir, and on a second end through plumbing to the surface of the ball IC. 
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     Referring now to FIG. 1, there is illustrated a ball semiconductor sensor  100  which is provided by a ball semiconductor, as described in a commonly-assigned U.S. Pat. No. 5,955,776 by Ishikawa entitled “Spherical Shaped Semiconductor Integrated Circuit,” which issued Sep. 21, 1999, and is hereby incorporated by reference. The broad medical capabilities of ball semiconductors are described more fully in a previously-filed U.S. patent application Ser. No. 09/448,781 by Ishikawa et al., entitled “Spherically-Shaped Biomedical IC,” filed Nov. 24, 1999, and which is hereby incorporated by reference. Briefly, the ball semiconductor  100  is approximately 1 mm or less in diameter, and is capable of receiving power from a distant source through radio frequency (RF) transmission, and sending data to an external receiver also via RF communication. They can also be physically connected to each other and to other devices. The RF signal generated by the ball semiconductor sensor  100  to carry the data stream outside the body is sufficiently strong to penetrate at least one centimeter of tissue. The ball semiconductor sensor  100  has onboard circuits comprising an RF antenna coil  118 , an RF rectifier-smoother  121 , an RF amplifier  122  and control logic  124 . 
     Referring now to FIG. 2, there is illustrated a first embodiment having a hydrogel  200  which is covalently attached to the surface of the ball sensor  100 . This hydrogel  200  is pH sensitive, and undergoes very large changes in volume with small changes in local pH. 
     Referring now to FIG. 3, there is illustrated an enzyme glucose oxidase  310  attached to the hydrogel  200 . The biologically active enzyme glucose oxidase  310  is covalently attached to the hydrogel  200 . Glucose molecules  320  are shown disposed proximate to the hydrogel  200 . This enzyme catalyzes the reaction                           
     Therefore, the change in acid concentration (measurable as a pH change) is directly proportional to the glucose concentration, as indicated in Equation (1). This allows the hydrogel  200  then to serve as a very sensitive glucose sensor. With the appropriate degree of cross-linking, the gel  200  can actually exert a contractile force on the ball  100  on the order of 10 4  dynes/cm 2 . This contractile force is large enough to be measured as a pressure exerted on the surface of the ball semiconductor  100  providing the sensor. This embodiment can therefore detect small changes in the local pH caused by the oxidation of glucose by the enzyme glucose oxidase  310 . To prevent shifts in pH due to other reasons from giving a false reading, an aggregate of two or more ball sensors  100  will always be used clinically, where one of the ball sensors  100  contains the glucose oxidase  310  enzyme and the other does not. Therefore, by examining the difference between the two ball sensors  100 , the effects due to the presence of glucose can be isolated. 
     Referring now to FIG. 4, there is illustrated the ball semiconductor sensor  100  with the attached hydrogel  200  in the presence of glucose molecules  320 . An osmotic pressure sensor  400  fabricated at or near the surface of the ball  100 , and proximate to the hydrogel  200 , has an osmotic chamber  402  and an electrode  404 , the purposes of which will be described in greater detail hereinbelow. 
     Refining now to FIG. 5, there is illustrated the ball semiconductor sensor  100  with the attached hydrogel  200  in the absence of glucose molecules  320 . The attached hydrogel  200  is shown in a collapsed state in the presence of a changed polarity on the surface of the ball  100 . The capability of changing the surface polarity of the ball  100  offers a control function over whether the ball sensor  100  can be used to either sense the presence of glucose molecules  320  when in a “blossomed” state (as indicated in FIG.  4 ), or can be prevented from sensing glucose molecules  320  when in a collapsed state. To accommodate this control feature, the ball sensor  100  has a polyelectrolyte hydrogel covalently attached to its surface. The polyelectrolyte is designed to collapse down tightly to the surface of the ball semiconductor  100  when the ball surface has an electrical charge of the opposite polarity as the polyelectrolyte. Conversely, when the charge on the ball  100  reverses polarity, the polyelectrolyte is repelled by the surface charge causing the hydrogel to quickly swell (or “blossom”) into the aqueous environment, and thereby promoting sensing of the designated chemical(s) in the surrounding environment. In this way, the sensing function is turned on and off with each change in the surface charge. 
     Referring now to FIG. 6, there is illustrated a ball semiconductor sensor  100  that has at least two osmotic capacitive pressure sensors  600  and  602  having respective osmotic chambers  604  and  606 . Osmotic chamber  604  has a first inner electrode  608  formed at its base, and a first outer electrode  610  formed on the surface of the ball  100 . Osmotic chamber  606  has a second inner electrode  612  formed at its base, and a second outer electrode  614  formed on the surface of the ball  100 . A first thin polymer semipermeable membrane  616  which is permeable to small molecules including both water, salts, and glucose, covers the entire surface of the ball  100 . This first polymer film  616  is permeable to small molecules including water, glucose and salts. A second semipermeable polymer film membrane  618  is applied over the osmotic pressure well  606 . The second membrane  618  overlies the first membrane  616 , and underlies the second outer electrode  614 . This second polymer film  618  is permeable to water and salts, but not to glucose. Therefore, well  606  contains water and salts, but no glucose, and well  604  contains water, salts, glucose, and other small molecules. 
     The two outer electrodes  610  and  614  are disposed on the outer periphery of the ball sensor  100 , with the first outer electrode  610  connected to the first membrane  616 , and the second membrane  618  interstitial to the first semipermeable membrane  616  and the second outer electrode  614 . The first outer electrodes  610  is applied to the top of the first polymer film  616  over the osmotic pressure well  604 , and the second outer electrode  614  is applied to the top of the second polymer film  618  over the osmotic pressure well  606 . The inner electrode  608  of the pressure sensor  600  connects to an input of a differential amplifier  620 . Similarly, the second inner electrode  612  connects another input of the differential amplifier  620 . As the contents of the osmotic pressure wells  604  and  606  change, the corresponding osmotic pressure and conductivity changes effect a change in the capacitance between the two sets of electrode pairs ( 608 / 610  and  612 / 614 ). By sending the output of these two capacitors  600  and  602  into the differential amplifier  620 , the output voltage will be proportional to the concentration of glucose being measured. 
     Referring now to FIG. 7, there is illustrated two ball sensors  100  and  101  disposed in a cluster. Ball sensor  100  includes a cathode  702 , an anode  704  and one or more interconnect bumps  706 . Similarly, ball sensor  101  includes a cathode  708 , an anode  710  and one or more interconnect bumps  712 . The bumps  706  and  712  electrically interconnect each of the balls sensors  100  and  101  when configured into a cluster. Notably, the ball  100  (or ball  101 ) may have several sets of interconnect bumps  706  strategically placed in various quadrants of the sphere of the ball  100  to facilitate interconnection to adjoining balls. Ball  100  has a hydrogel  714  and enzyme glucose oxidase  716  combination (similar to hydrogel  200  and glucose oxidase  310 ) disposed in selected areas thereon, and ball  101  also has a hydrogel  718  and enzyme glucose oxidase  720  combination (similar to hydrogel  200  and glucose oxidase  310 ) disposed in selected areas thereon. As mentioned hereinabove, where a cluster of balls  100  are used, one of the balls  100  (or  101 ) may not incorporate the oxidase  310  in order to provide a reference against that parameter which is being measured, in this case, glucose. 
     Referring now to FIGS. 8 and 9, there are illustrated graphs indicating the volume of the hydrogel  200  as a function of the change in pH (in FIG.  8 ), and a graph showing the anticipated sensed pressure as a function of pH changes (in FIG.  9 ), which will be proportional to graphing pressure changes as a function of glucose concentration if glucose oxidase  310  is attached to the hydrogel  200 . Because of the rapid rate of change of volume with respect to pH, this embodiment provides near step function output signals  800  and  900 , as shown in FIGS. 8 and 9. Therefore, this sensor  100  is ideal to drive an insulin pump, giving sharp on/off signals to the pump mechanism. 
     Referring now to FIG. 10, there is illustrated a ball semiconductor sensor  100  having a well (or chamber, similar to chambers  604  and  606 )  1000  for electrochemical detection of glucose using a pH sensitive hydrogel coupled with an electrically conductive polymer. A polymer composite  1002  placed in the well  1000  consists of the pH-sensitive hydrogel  200 , an electrically conductive polymer, and the enzyme glucose oxidase  310 . The pH-sensitive hydrogel  200  is cross-linked with the electrically conductive polymer composite  1002  (e.g., polyaniline) that also swells in water. The enzyme glucose oxidase  310  is covalently attached to this polymer composite  1002 , which is then attached to the surface of an inner electrode  1004  (similar to inner electrodes  608  and  612 ) at the bottom of the well  1000  at the surface of the semiconductor substrate  1006 . A semipermeable membrane  1008  (similar to the first membrane  616 ) is attached across the top of the well  1000 , forming the tightly sealed electrochemical chamber  1000 . 
     An outer electrode  1010  (similar outer electrodes  610  and  614 ) and the inner electrode  1004  together form a parallel plate capacitor. The outer electrode  1010  is attached to the semipermeable membrane  1008 , forming the parallel plate capacitor, which is connected to an LRC circuit (not shown in FIG.  10 ). The LRC circuit preferably detects changes in glucose levels by shifts in the natural frequency of the circuit. As glucose diffuses into the chamber  1000 , it will react with the glucose oxidase  310 , change the pH within the chamber  1000 , and hence change the volume of the hydrogel composite  1002 . As the volume of the hydrogel composite  1002  changes, the electrically conducting polymer is brought nearer to the top outer electrode  1010 . This changes the effective capacitive distance, which is detected as a change in the frequency of the LRC circuit. Therefore, changes in the glucose level are directly measured as frequency changes in the electronic circuitry of the semiconductor. 
     In another embodiment, the relative change in osmotic pressure is utilized as a sensitive measure of glucose concentration, as demonstrated in U.S. Pat. No. 5,337,747 by Neftel, entitled “Implantable Device For Estimating Glucose Levels,” and issued Aug. 16, 1994. It has been shown that the major changes in the contents of the interstitial fluid involve a limited number of substances, one of which is glucose. Furthermore, it has been shown that interstitial glucose levels closely follow blood glucose levels. Therefore, the relative osmotic pressure through a semipermeable membrane that allows glucose to pass with respect to a semipermeable membrane that excludes glucose will provide an accurate measure of the interstitial glucose level. Using two membranes will control for changes in interfering substances, changes in patient hydration states and other confounding situations. 
     In another embodiment, a platinum sensor is attached to the surface of the ball. This electrode amperometrically senses the concentration of hydrogen peroxide generated as per Equation (1) above. Once hydrogen peroxide is generated, it is electrochemically detected according the formula of Equation (2):                           
     at +600 mV vs Ag/AgCl. Therefore, the current generated is proportional to the amount of hydrogen peroxide generated, which is proportional to the glucose concentration. The problem with this approach is the presence of interfering substances such as ascorbic acid, dopamine, acetaminophen and uric acid. To help with selectivity, a 3-mercaptopropyltrimethoxysilane coating is applied to the platinum. The enzyme glucose oxidase is then immobilized on the mercaptosilane. This is then coated with a semipermeable membrane such as polyurethane. A silver electrode is treated in a similar manner but without enzyme immobilization to serve as a reference. 
     Referring now to FIG. 11, there is illustrated the basic circuit functions of the ball sensor  100 . The spherical semiconductor ball  100  is provided having a substrate upon which the transponder circuitry is disposed, and includes an antenna/coil  1111 , which serves the dual purpose of receiving signal energy from a remote central processing unit  1120  and transmitting signal energy thereto. The signal energy may be received by the antenna/coil  1111  by inductive coupling if the central processing unit  1120  is sufficiently close to the ball  100 . Alternatively, electromagnetic waves can be used to transmit power from the central processing unit  1120  to the ball  100 , whereby the magnetic field component of the electromagnetic wave induces a current in the coil  1111 , in accordance with known techniques. The power signal received by the antenna/coil  1111  is rectified and smoothed by an RF rectifier smoother circuit  1112 . The output of the rectifier circuit  1112  is connected to a DC power storage device  1113 , such as a capacitor. Such capacitor might also perform a waveform smoothing function. A voltage regulator  1114  is used to make the DC voltage stable regardless of the distance between the central processing unit  1120  and the ball  100 . 
     An RF oscillator  1117  generates an RF carrier signal at a predetermined frequency in the RF band. An RF modulator  1118  modulates onto the carrier frequency signal one or more of the sensor data corresponding sensor(s)  1109  via an analog-to-digital (A/D) converter  1110 , and information from a memory  1115  which has stored therein an ID code as a digital word. Notably, the memory  1115  may have the capacity to store more information, such as the date, time, patient name and address, physician name, etc., to facilitate the recording of pertinent patient/doctor information. The resulting modulated signal is amplified by an RF amplifier  1119 , and then transmitted to the outside through the antenna/coil  1111 . Further details of the preferred coil are described in the aforementioned commonly assigned U.S. patent application Ser. No. 09/448,642 by Ishikawa et al., entitled “Miniature Spherical-Shaped Semiconductor With Transducer” and filed Nov. 24, 1999. 
     The external central processing unit  1120  includes an antenna/coil  1121  that serves the dual purpose of generating the electromagnetic wave for transmitting power to the ball  100 , and receiving the RF data signal transmitted by the ball  100 . It is preferred that the frequency of the electromagnetic wave that is output by the antenna/coil  1121  is different from the carrier frequency generated by the RF oscillator  1117 . An RF amplifier  1122  is used to couple the electromagnetic wave for power transmission to the antenna/coil  1121 . An RF oscillator  1123  determines the frequency of the electromagnetic wave that is emitted by the central processing unit  1120 . The data received by the antenna/coil  1121  is detected by an RF detector  1124  and then amplified by an RF amplifier  1125 . Preferably, the converter  1126  converts the signal from the RF amplifier  1125  to a digital signal, which in turn is input to control logic  1127 . The control logic  1127  may be a smaller central processing unit which interfaces with another main processor of the main central processing unit  1120 . The control logic  1127  extracts the data from the signal received by the central processing unit  1120  from the ball  100  and displays that information on a suitable display  1128 , such as a CRT screen. 
     The technique for transmitting data from the ball  100  to the main central processing unit  1120  using the carrier frequency generated by the RF oscillator  1117  can be in the form using any suitable protocol. The modulation can be AM, FM, PM, or any other suitable modulation technique. 
     Referring now to FIG. 12, there is illustrated a schematic block diagram of the ball sensor  100  and the remote system for the powering/detection operation. The illustrated embodiment of FIG. 12 is that associated with a “passive” system, which term refers to the fact that there is no battery associated therewith. In order to operate the system, there is provided an inductive coupling element  1204  in the form of an inductor, which is operable to pick up an alternating wave or impulse via inductive coupling and extract the energy therein for storage in the inductive element  1204 . This will create a voltage across the inductive element  1204  between a terminal  1206  and a terminal  1208 . A diode  1210  is connected between the node  1208  and a node  1212 , with the anode of diode  1210  connected to node  1208  and the cathode of diode  1210  connected to a node  1212 . Typically, the diode  1210  will be fabricated as a Schottky diode, but can be a simple PN semiconductor diode. For the purposes of this embodiment, the PN diode will be described, although it should be understood that a Schottky diode could easily be fabricated to replace this diode  1210 . The reason for utilizing a Schottky diode is that the Schottky diode has a lower voltage drop in the forward conducting direction. 
     The diode  1210  is operable to rectify the voltage across the inductive element  1204  onto the node  1212 , which has a capacitor  1214  disposed between node  1212  and node  1206 . Node  1212  is also connected through a diode  1216  having the anode thereof connected to node  1212  and the cathode thereof connected to a node  1218  to charge up a capacitor  1220  disposed between node  1218  and  1206 . The capacitor  1220  is the power supply capacitor for providing power to the ball sensor  100 . 
     A CPU  1238  and a clock circuit  1240  are provided for providing processing and timing functions to the system. A memory  1239  (similar to memory  1115 ) is provided in communication with the CPU  1238  for storage of an ID unique to the ball sensor  100  to allow the CPU  1238  to retrieve this information for transmittal back to the remote location  1120 . This retrieval is automatic when the system is powered up and is continuous as long as the system is powered. This memory  1239  is non-volatile, such as a ROM, or it could be a programmable non-volatile memory. 
     In order to communicate with the CPU  1238  for transferring data therefrom, a transmit circuit  1242  is provided for interfacing to node  1212  through a resistive element  1244 . This allows energy to be transmitted to node  1212 . It is important to note that the semiconductor junction across diode  1210  is a capacitive junction. Therefore, this will allow coupling from node  1212  to node  1204 . Although not illustrated, this could actually be a tuned circuit, by selecting the value of the capacitance inherent in the design of the diode  1210 . In any event, this allows an RF connection to be provided across diode  1210  while allowing sufficient energy to be input across inductive element  1204  to provide a voltage thereacross for rectification by the diode  1210  and capacitor  1214 . Typically, the frequency of this connection will be in the MHz range, depending upon the design. However, many designs could be utilized. Some of these are illustrated in U.S. Pat. No. 4,333,072 by Beigel, entitled “Identification Device” issued Jun. 1, 1982, and U.S. Pat. No. 3,944,982, by Mogi et al., and entitled “Remote Control System For Electric Apparatus” issued Mar. 16, 1982, both of which are hereby incorporated by reference. With these types of systems, power can continually be provided to the node  1212  and subsequently to capacitors  1214  and  1220  to allow power to be constantly applied to the ball sensor  100 . 
     The remote system  1120  includes an inductive element  1250  which is operable to be disposed in an area proximate to the ball sensor  100 . The inductive element  1250  is driven by a driving circuit  1252  which provides a differential output that is driven by an oscillator  1254 . This will be at a predetermined frequency and power level necessary to couple energy from inductive element  1250  to inductive element  1204 . Since the remote system  1120  is an external system, the power of the oscillator  1254  can be set to a level to account for any losses encountered in the scanning operation. 
     When the information is received from the ball sensor  100 , it is superimposed upon the oscillator signal driving the inductive element  1250 . This is extracted therefrom via a detector  1260  which has the output thereof input to a first low pass filter  1262  and then to a second low pass filter  1264 . The output of low pass filters  1262  and  1264  are compared with a comparator  1266  to provide the data. The filter  1262  will provide an average voltage output, whereas the filter  1264  will provide the actual digital voltage output. The output of the comparator  1266  is then input to a CPU  1270  which also is powered by the oscillator  1254  to process the data received therefrom. This can be input to a display  1272 . 
     Referring now to FIGS. 13A and 13B, there are illustrated alternate embodiments for the transmit/receive operation. In FIG. 13A, there is provided an oscillator  1300  which drives an external inductive element  1302 . Typically, there is some type of load  1304  disposed across the inductive element  1302 . This is the primary power that is provided to the system. A separate inductive element  1306  is provided on the ball sensor  100 , for being inductively coupled to the inductive element  1302 . Thereafter, a voltage is generated across the inductive element  1306 , the inductive element  1306  being connected between a node  1308  and  1310 . A diode  1312  is connected between node  1308  and a power node  1314 , and a power supply capacitor  1316  is disposed between node  1314  and node  1310 . This allows the voltage on node  1306  to be rectified with diode  1312 . 
     The receive operation in this embodiment in FIG. 13B utilizes a separate inductive element or antenna  1324  in the ball sensor  100 , which is operable to be connected between nodes  1309  and  1310 . Node  1309  is capacitively coupled to a transmit node  1330  with a capacitor  1332 , the capacitor  1332  being a coupling capacitor. A transmitter  1334  is provided for transmitting received data from a line  1336  to the node  1330  which is then coupled to the node  1309  to impress the RF signal across the inductive element  1324 . 
     A corresponding inductive element  1340  is disposed on the external remote controller, which inductive element  1340  is operable to be disposed proximate to the inductive element  1324 . The inductive element  1340  is basically a “pick-up” element which is operable to receive information and function as an antenna and provide the received signal to a receiver  1342 . The structure of FIG. 13 b  is a separate structure, such that node  1309  is isolated from node  1308 , the power receiving node. However, it should be understood that any harmonics of the oscillator  1300  would, of course, leak over into the inductive element  1306 . This can be tuned out with the use of some type of tuning element  1344  on the ball sensor  100  disposed across inductive element  1324  and also a tuning element  1346  disposed across the inductive element  1340 , i.e., the antenna. 
     Referring now to FIG. 14, there is illustrated a perspective view of the spherical IC embodiment of the ball sensor  100 , wherein the inductive element  1204  is illustrated as being strips of conductive material wrapped around the exterior of the spherical ball IC  100 . The inductive element  1204  described hereinabove with respect to FIG. 12, is formed of a conductive strip  1401  wrapped many times around the spherical ball sensor  100 . The length of these wires depends upon the receive characteristics that are required. As described hereinabove with reference to FIGS. 13A and 13B, there could be multiple conductive strips  1401 , each associated with a receive function, a transmit function or a power function, or they could all share one single conductive element or strip. On one end of the spherical ball sensor  100 , there is provided an interconnect pad  1400  and conductive interconnect balls  1402  associated therewith of material such as gold. On the other end thereof are provided additional interfacing interconnect balls  1404 . These interconnect balls  1402  and  1404  allow the spherical IC ball sensor  100  to be clustered with other spherical ICs. The contacts or interconnect balls  1402  and  1404  and the clustering operation are described in U.S. Pat. No. 5,877,943 by Ramamurthi, entitled “Clustering Adapter For Spherical Shaped Devices” issued Mar. 2, 1999, and assigned to the present assignee, which is hereby incorporated by reference. 
     Referring now to FIG. 15, there is illustrated a cross-sectional diagram of the surface of the spherical IC ball sensor  100  illustrating the conductive strips forming the inductive element  1204 . The conductive strips are referred to by reference numeral  1510  which are spaced on or near the surface of the IC ball sensor  100  by a predetermined distance and separated therefrom by a layer of silicon dioxide  1508 . A passivation layer  1509  is then disposed over the upper surface of the conductive strips  1510 . The conductive strips  1510  can be fabricated from polycrystalline silicon but, it would be preferable to form them from the upper metal layer to result in a lower conductivity strip. This will allow the strips  1510  to be narrower and separated from each other by a larger distance. This separation would reduce the amount of capacitance therebetween. 
     One end of the strips  1510  is connected to a diode structure  1511 . The diode structure  1511  is formed of an N-well implant region  1514  having an interface  1512  with the underlying substrate, and into which a P-well implant region  1516  is disposed, and an N-well implant region  1518  disposed within the P-well implant region  1516 . This forms a PN diode where one end of the conductive strips  1510 , a conductive connection  1520 , is connected to the P-well  1516  implant region, and a conductive layer  1522  is connected at one end to the N-well implant region  1518 . This conductive layer or strip  1522  extends outward to other circuitry on the integrated circuit and can actually form a capacitor (e.g., capacitors  1214  or  1220 ). Since it needs to go to the capacitor directly, a lower plate  1524  formed of a layer of polycrystalline silicon or metal in a double-metal process, could be provided separated therefrom by a layer of oxide  1526 . 
     Referring now to FIG. 16, there is illustrated a side view of an alternative embodiment utilizing additional circuitry or structure attached to the ball IC  100  for providing a local power source. As described hereinabove, the ball IC  100  requires a power-generating structure for storing a power supply voltage such that diodes must be provided for receiving and rectifying a large amount of power and charging up a power supply capacitor. Alternatively, the ball IC  100  could be configured to interface to an attached local power supply system  1600  comprising either a battery or a capacitor. The local power supply system  1600  is illustrated as disposed on a circuit board  1603  defined by supporting structures  1602  and  1604 . The circuit board  1603  contains electronics for interfacing the local power supply system  1600  to the ball IC  100 . 
     Referring now to FIG. 17, there is illustrated a schematic block diagram of the ball IC  100  using a battery as the local power supply system  1600 . A battery  1701  (or local power source similar to  1600 ) is provided as a source of self-contained power and is connected across a capacitor  1700  to provide smoothing of any power output to the system power-consuming elements of the ball IC  100 . Power for all onboard components is obtained from the SYSTEM POWER output by providing sufficient charge to the capacitor  1700 . The capacitor  1700  could be formed on the surface of the ball IC  100  or it could actually be part of the battery structure  1701 . Additionally, the capacitance  1700  could actually be the capacitance of the battery  1701 . Additional structure could be provided for powering the CPU  1238  and the other circuitry on the ball IC  100  from the battery  1701 . As such, there would only be required a smaller inductive element  1702  (similar to inductive element  1204 ) and a capacitor  1704  to allow the receive/transmit block  1242  to receive/transmit information from and to the remote exterior control station  1120 . A switch control  1730  controls the gate of a switching transistor  1731  to switch the output of the transducer  1109  through the switching transistor  1731  source/drain path to the CPU  1238 . 
     Each of the above-described sensing techniques can be implemented on the same system of printed integrated circuits. This system comprises one or more physical semiconductors that are connected into a single unit. This expands the capabilities of the described systems in two ways. First, a single biological molecule can be detected by more than one sensor, using different sensing mechanisms. This has the advantage that if one or more different types of sensors begin to degrade in performance with time, that sensor&#39;s performance can be monitored. If needed, that sensor can either be uncoupled from the system, in the case of sensor failure, or it can be re-calibrated in situ based upon the readings of other sensors, whose readings are considered stable, or by an outside sensor brought in specifically for the purpose of re-calibration. The second advantage of combining various sensing techniques, is the ability to sense several different biological molecules at the same time. This multi-chemical biosensor has the ability to take general health status readings, and flag chemical imbalances. 
     Referring now to FIG. 18, there is illustrated a side elevation of a cluster  1880  of semiconductor balls that may be employed in a sensor function, according to a disclosed embodiment. Although a single ball can include the foregoing functions, more complex monitoring functions with multiple sensors (or transducers) can be implemented. For example, the cluster  1880  can include a ball  1881  for power receiving and data transmission functions. Alternatively, ball  1881  can be a miniature battery. A ball  1882  can include a first transducer function, such as glucose sensing, and a ball  1883  can include a second transducer function, such as measuring pH, pO 2 , pCO 2 , or temperature, as the particular application requires. Connections between the balls are made through metal contacts  1890 , which may be solder bumps. 
     Referring now to FIG. 19, there is illustrated a cross section taken along the line  19 — 19  of FIG. 18 to expose the four contacts  1988   a ,  1988   b ,  1988   c  and  1988   d  between ball  1882  and ball  1883 . The contacts  1988   a  and  1988   b  may be power contacts, such as a positive 3.0 volts and ground, which can be passed from ball  1881  around ball  1882  by conductors on its surface using two of a group of similar contacts (designated collectively by numeral  1890  in FIG.  18 ). The contacts  1988   c  and  1988   d  may be data and control contacts for communications between ball  1882  and ball  1883 . Similarly, data and control contacts may exist among contact group  1890  between ball  1881  and ball  1882  to the extent needed. 
     Referring now to FIG. 20, there is illustrated a cluster or aggregation  2000  of balls  2091 ,  2092 ,  2093 ,  2094 ,  2095  and  2096 , as an example of the versatility of such ball systems. The cluster  2000  specifically shows six balls arranged in a three-dimensional configuration. It will be appreciated that various other cluster arrangements are possible, limited only by the constraints of the end-use application. Each of the balls of the cluster  2000  can perform different electronic functions and communicate with each other through contacts as described above in connection with FIGS. 18 and 19. For example, ball sensors can be located on the sides of catheters to measure various parameters. More than one of the balls in the cluster  2000  can also be operable to perform a glucose sensing function. Clustered balls are able to integrate, transmit, and receive more complex information or actuate a response (emit laser, infrared, ultrasound, or electrical energy). The actuators may contain a piezoelectric driver attached to a ball surface for ultrasound generation and control for measurements of luminal diameter and fluid flow rate within the vessel lumen. Such actuators can serve as an emitting device allowing for external detection to determine location or position. 
     Referring now to FIG. 21, there is illustrated one embodiment where a ball IC  2110  is constructed with a pump  2140  that is connected on one end through plumbing  2130  to reservoir  2120 , and on a second end through plumbing  2150  to the surface  2115  of the ball IC  2110 . A medicine or substance (e.g., glucose) carried by the ball IC  2110  in reservoir  2120  to a treatment site can be released to the site through plumbing  2130  and  2150 . The action of pump  2140  is responsive to signals generated by control logic  1116 , shown in FIG.  11 . The disclosed method and apparatus are provided as an implantable system for the delivery of medication or substances locally to a site. However, it can also be engineered to deliver systemically acting substances such as insulin or in response to certain levels of detected substances such as glucose. The ball  2110  can also accommodate one or more actuator devices which release pharmaceuticals and/or bio-pharmaceuticals for gene therapy. 
     Above are described several embodiments, each of which is a unique method by which a biological molecule may be detected. The descriptions have all used the specific example of glucose, but it should be kept in mind that any biological molecule that undergoes similar enzymatic reactions can also be detected by these same means. 
     Although the preferred embodiment has been described in detail, it should be understood that various changes, substitutions and alterations can be made therein without departing from the spirit and scope of the invention as defined by the appended claims.