a detailed description of illustrative embodiments of the present invention will now be described with reference to fig1 - 17 . although this description provides a detailed example of possible implementations of the present invention , it should be noted that these details are intended to be exemplary and in no way delimit the scope of the invention . sensor : any element that can be used to transduce a biological signal into an electrical or other signal . examples of sensors include : electrical contacts for recording electrophysiological signals , optical detectors for recording light correlates of biological activity , chemical sensors for detecting changes in chemical concentrations or ph ( e . g ., chloride , neurotransmitters , lactate , glucose , other metabolites , neuro - active compounds , medications , biological substances such as tumor - secreted factors , etc . ), devices for measuring temperature , force , acceleration , movement , pressure , etc . effector : any device that takes a signal and introduces an intervention to modulate biological ( e . g ., brain ) activity . examples of effectors include electrical stimulators , photo / light - emitters ( e . g ., for activating brain tissues impregnated with a light responsive compound ), chemical releasing / infusion devices , devices that change temperature , pressure , and / or acceleration , and devices that introduce electrical , magnetic or other fields , etc . illumination sources such as a light source or other source that can activate tissue for diagnostic or monitoring purposes may also be used . for example , such illumination sources may be used to activate brain tissue to interrogate its function but not necessarily to modulate its activity . in the following specification , the term “ sensor ” will be understood to also include functionality of the effector as defined above . while exemplary embodiments of the invention are described herein in the context of a system of intracranial electrodes to record from and stimulate the brain , those skilled in the art will appreciate that the invention may also be used as a configurable sensor and / or effector in the following types of biological systems . the following list is not meant to be exhaustive , but rather representative of the broad array of monitoring and modulation functions that can be subsumed by the invention : cardiac sensors / effectors , such as for cardiac electrophysiology testing , and devices such as pacemakers , defibrillators , electrically active catheters for going inside the heart and blood vessels , and the like ; neuroprostheses for special sensory organs , e . g . artificial retinas , cochlear implants , balance ( vestibular and other cranial nerve interfaces ) prostheses , devices to aid in taste , smell , physical sensation , proprioception , and other similar functions ; neuroprostheses for recording and functional electrical stimulation of motor and other central and peripheral nerves for afferent and efferent functions ( e . g . motor and sensation ); implanted devices to go into tissues , such as intravascular and other forms of sensor / effector covered stents for deployment in the brain or blood vessels ; implantable devices for organ function monitoring , or monitoring of tissues for the presence or recurrence of tumors , cancer , metastases , etc . ; implantable sheets of electrodes that can be wrapped around structures for patterned recording , stimulation or other functions , for example , pacing stomach or intestinal contractions to restore mobility to paralyzed tissues ( e . g . due to diabetic gastroparesis ); and endoscopic introduction into other cavities in the body , for example , in and around the heart , abdomen , inside organs , on muscular structures such as the bladder neck , inside blood vessels , on stents , etc . at the outset , the inventors recognize that to sample hundreds or thousands of electrodes simultaneously , a multiplexing strategy is desired to reduce the number of wires that must come off of the electrode array . reducing the number of wires coming off of the array is also advantageous because the number and size of leads implanted along with an electrode array has been found to correlate with risk of infection , brain swelling , and complications from implantation surgery . in addition , having electrode arrays with hundreds of connections greatly increases the probability of operator error in making the connections and properly setting up the labels on each channel . electrode array embodiments that embody exemplary multiplexing embodiments will be described in the following section . in an exemplary embodiment of the present invention , individual buffer amplifiers are incorporated at each electrode and their outputs are multiplexed together . this design is illustrated in fig6 . each electrode contact 100 is directly attached to a dedicated preamplifier 110 that provides some gain to the signal and a low - output impedance to drive the column line 120 . the output of the preamplifier 110 is connected to the column line 120 through an analog switch 130 . the circuit details of the analog switch are shown in fig7 . the nmos pass transistor 131 is driven by a digital logic signal , c , while the pmos pass transistor 132 is driven by the output of the inverter 133 . in this way , both pass transistors are active ( conducting ) when c is at a high logic level and both pass transistors are inactive ( non - conducting ) when c is at a low logic level . this allows analog signals to either pass through the device or not based on a digital logic control signal , c . alternatively , fig1 illustrates one possible embodiment of the analog switches utilized in fig1 where the analog switch 130 is coupled to a static ram cell 134 to maintain the switch state ( open or closed ) without intervention by the system logic . fig6 shows columns of n electrodes 100 , preamplifiers 110 and analog switches 130 . by activating a specific row signal 140 and de - activating the other n − 1 row signals , the output of the selected row amplifier will be allowed to drive the column line 120 . in this manner , any one of the n rows can be selected to drive the column amplifier 150 . this column amplifier 150 provides additional gain to match the range of the signal to the input range of the column analog to digital converter 160 . the column analog to digital converter 160 converts the analog signals from the electrode channels to digital values . the digital output of the column analog to digital converter 160 is connected to a digital buffer 170 , and the outputs of all n digital buffers 170 ( one for each column ) are connected together . each column signal 120 can be individually selected via the n column select signals 180 . in this way , the data from the n column analog to digital converters 160 can be combined down to one digital input on the integrated microprocessor 190 . fig8 illustrates one possible embodiment of the circuit shown in fig6 . the circuit has been simplified to only show the amplifiers and analog switches for 4 electrodes , arranged in a small grid of 2 × 2 . however , fig6 illustrates how this basic design can be extended to any number of rows and columns . in fig8 , the amplifier has been implemented using a source - follower architecture . in this configuration , three nmos transistors 300 have been connected as a current source . two additional nmos transistors 310 and 320 are configured as a current mirror and a final nmos transistor 330 forms the active load . these six transistors comprise the amplifier ( 110 in fig6 ). the output of this amplifier is connected to a multiplexing transistor 340 ( 130 in fig6 ) which serves to selectively enable the output of that amplifier . in an alternate embodiment of the invention , a cmos digital image sensor has been modified to multiplex the electrodes 100 . as illustrated in fig9 , such a modified cmos image sensor 200 includes an array of electrodes 100 that are connected to output amplifier 210 and addressed by suitable addressing circuitry 250 . in an exemplary embodiment , an analog to digital converter 225 may be connected to the output of output amplifier 210 so as to provide a / d conversion on the image sensor array 200 . correlated double sampling may be removed to prevent inadvertent stimulation of the cortex during the reset operation . further modifications may be required to reduce the noise floor of the image sensor array 200 . the cmos image sensor of fig9 works as follows . each microelectrode 100 is connected to the gate of a field effect transistor 220 of amplifier 230 . this transistor 220 is connected to the common vertical bias transistor 240 by means of a horizontal row select transistor 250 . in this way , one half of an amplifier is formed at each pixel and the other half is shared among all the pixels in a given column . another similar configuration allows a given column to be selected to drive the output amplifier 210 . this high bandwidth amplifier 210 provides the gain required to match the detected eeg signals to the range of the analog to digital converter 225 that samples the signal and outputs the digital data over a single low - voltage differential signaling ( lvds ) high speed serial data bus 260 . for example , a commercially available 10 - bit , 20 msps analog - to - digital converter 225 may be used that operates using less than 50 mw so that it may be integrated onto the electrode array 200 to provide an output bit stream for recording and storage . in another alternate embodiment , a ccd , or charge coupled device , is modified in its design to accept direct electrical input , instead of light input . in this modality , the eeg signal creates packets of charge in the device that are transferred along the device , until ultimately read out . the flexible electrode arrays described above and illustrated in fig6 and 9 include n 2 electrodes . these electrodes can be many possible types of electrodes . for example , the electrodes 100 may be made of gold , platinum , platinum - iridium , tungsten or other substances including conductive non - metals . the electrodes 100 may be in the shape of “ bumps ”, flat round or square patches , or small penetrating spikes . other embodiments of the “ tissue end ” of this electrode system may penetrate tissue ( e . g . brain ) using tetrodes , silicon and platinum microelectrode arrays and silicon microprobes , among others . additionally , the electrodes 100 do not need to be electrodes at all . some or all of the electrodes 100 may be replaced with other solid - state sensors that can be designed to output an electrical signal . for example , fig1 shows a variation of the circuit of fig6 where some of the electrodes 100 have been replaced by photodiodes 270 . with an appropriate illumination source , these light sensors 270 could be used to measure local blood oxygen concentration , blood flow , or other parameters . other solid - state sensors that could be integrated onto the array in place of one or more electrodes to measure local chemical concentrations , ph , temperature , force , magnetic field and more . the analog switch 280 of fig1 placed between adjacent micro - electrodes 100 allows the creation of electrically connected contacts of arbitrary size . for example , if the following switches in the example schematic are programmed as follows : active inactive r0c0 , r0c2 r0c1 r1c0 , r1c1 , r1c2 , r1c3 r2c1 r2c0 , r2c2 r3c0 , r3c1 , r3c2 , r3c3 r5c0 , r5c1 , r5c2 , r5c3 r4c1 r6c0 , r6c2 r6c1 then the resulting effective circuit will be the circuit shown in fig1 . the net result of this transformation is a 4 × reduction in spatial sampling . this would allow a 4 × increase in sampling rate or bit depth or a similar reduction in power consumption . further spatial aggregation would be possible as well , right up to or beyond the size of current macro electrodes . a dynamic algorithm could be employed that would intelligently combine and dissociate electrodes such that areas of interest could be automatically identified and spatially sampled at a higher density while areas of less interest could be sampled at a lower density . furthermore , the sampling sites could be customized such that areas that do not need to be sampled , like vasculature , could be ignored . this might be done , for example , by taking a digital picture of the area to be recorded , or abstracting this from an mri image , and then programming the electrode array to record only from those electrodes in contact with regions of interest , or to silence contacts positioned over electrically inactive regions . it is important to note that being able to customize sensor / stimulator size by aggregating a number of electrodes , may have distinct neurophysiological advantages based upon features of the cortical or subcortical structure or network being recorded or stimulated . for example , if a group of contiguous cortical columns of a particular dimension is the basic functional unit that needs to be monitored or stimulated , this structure might best be recorded or stimulated with electrodes aggregated into groups of 4 or 16 , rather than single contacts . similarly , if a single cortical column need be activated , this might be best done with single contacts , or aggregated contacts from a system in which the electrodes are more closely spaced . an additional overlay of demultiplexing logic plus a digital to analog converter ( 160 of fig6 ) can be added to the electrode array to allow micro - stimulation at one or more contact sites . the intelligence may also be provided in an interface or a remote processing unit , as desired . the stimulation for the electrodes may be pre - programmed patterns developed to accomplish particular tasks , such as to modulate epileptiform activity , initiate or inhibit function , map blood vessels , and map functions of neural tissue . in other applications , stimulation might be controlled in closed loop , via active software , based upon recorded signals or using continuous feedback to modulate neuronal activity for therapeutic purposes . an additional microprocessor or digital signal processor 190 can be added to the electrode array of fig6 to enable its use as a stand - alone closed - loop control system . this system would incorporate a sampling control system , signal processing , and a stimulation control into the microprocessor or digital signal processor 190 to allow the electrode array to become a fully self - sufficient implantable device . the processor 190 may include algorithms to provide for vessel or functional brain imaging , location and recording , and to track the position of respective electrodes and identify migration of the electrodes 100 within cortical tissue . in order to conserve battery life , the number of channels sampled can be reduced to only the channels that are of most interest and clinical value . the other amplifiers on the array can be shut down or only sampled periodically to reduce power consumption and data processing requirements . this embodiment also allows for periodic updating of the electrodes used as networks evolve and function changes or migrates over time . of course , hardware and software tools may be implemented in conjunction with the electrode arrays described herein to collect , analyze , and display the multi - channel , broadband neurophysiological signals detected by the electrode arrays of the invention . a conventional neural amplifier occupies 0 . 16 mm 2 of space using a very conservative 1 . 5 um - cmos process ( harrison r & amp ; charles c ., “ a low - power low - noise cmos amplifier for neural recording applications ,” ieee journal of solid - state circuits , ( 2003 ) vol . 38 , pp . 958 - 965 ). to achieve a 100 × 100 array in 36 cm 2 , each amplifier must occupy less than 0 . 36 mm 2 of space . this means that using a similar design would leave & gt ; 55 % of the surface area available for interconnects and other logic , which should make the design feasible . a 100 × 100 grid array will contain 10 , 000 electrodes . sampling each electrode at 2000 hz will yield a total sampling rate of 20 msps . at 12 bits / sample , this yields 30 mb / s of data . this becomes 101 gb / hr and 2 . 4 tb / day . however , a simple differential encoding scheme should be able to reduce this data set by at least a factor of 4 . considering that 1 tb single hard drives are currently available and that hard drive prices continue to fall , this amount of data seems large but manageable . if needed , the data can be down - sampled and the recording can be adjusted to the task as required . for example , the patient could be recorded at a sampling rate of 500 hz per channel at rest and automatically adjusted to 2 khz per channel synchronized with particular cognitive tasks or periods of increased probability of seizure onset . another strategy would be to collect data at the best quality all the time and then utilize a background server task that compresses , prunes and archives data to be saved . once the data is converted from analog to digital , the samples need to be transmitted to a computer for storage and analysis . this link needs to use as few wires as possible , while consuming little power and providing a reasonable cable length , interference tolerance and room to expand to larger array sizes . the use of an lvds link ( 260 of fig9 ) reduces the power consumption of the data transmission , reduces radiated electromagnetic noise and allows data transmission of up to 1 gigabit per second and beyond over a single pair of wires . at the current estimated data rate of 240 mbps , several transmission techniques should be capable of performing this task . among them are usb 2 . 0 , firewire 400 / 800 , esata and gigabit ethernet . as an example , a usb 2 . 0 interface chipset with integrated microprocessor ( see ez - usb fx21p ™ usb microcontroller at http :// download . cypress . com . edgesuite . net / design_resources / datasheets / contents / cy7c68013a — 8 . pdf ) consumes 165 mw of power while delivering up to 53 mb / s data transfer rate . this should be sufficient for integration into a device . if further power savings are required , a custom low - voltage differential signaling ( lvds ) protocol can be designed that can attempt to better meet the needs presented by this electrode array . a calculation of the maximum allowable power consumption can be estimated from the simulations presented by ibrahim t s , abraham d & amp ; rennaker r l in “ electromagnetic power absorption and temperature changes due to brain machine interface operation ,” ann biomed eng ., ( 2007 ) vol . 35 : pp . 825 - 834 . the study concludes that 78 mw / cm 2 is an allowable power dissipation for a 1 degree celsius temperature rise . another work states that a heat flux of only 80 mw / cm 2 can cause tissue damage ( t m , harasaki h , saidel g m & amp ; davies c r , “ characterization of tissue morphology , angiogenesis , and temperature in the adaptive response of muscle tissue to chronic heating ,” lab invest . ( 1998 ), vol . 78 , pp . 1553 - 1562 ). a current design low - power amplifier for neural recordings consumes 15 μw per channel ( aziz j , karakiewicz r , genov r , chiu a , bardakjian b , derchansky m & amp ; carlen p ., “ in vitro epileptic seizure prediction microsystem ,” circuits and systems , 2007 , iscas 2007 . ieee international symposium on ( 2007 ), pp . 3115 - 3118 ). this means that a 10 , 000 channel electrode array might consume 150 mw of power . if these 10 , 000 channels are spread out over a 36 cm 2 electrode array , the threshold for damage might be as high as 2 . 88 w . therefore , 150 mw may be an acceptable level of power consumption . to improve the safety of the device , solid state temperature sensors could easily be integrated into the array to measure thermal rise . if an unsafe temperature rise is measured , the array sampling rate can be turned down to reduce power . if this fails to control the temperature rise , the array can be completely turned off . additionally , the power consumed by all the active elements on the array should be considered as well . if the power consumed by the amplifiers , analog to digital converter ( s ), microprocessor and interface logic ( table 1 ) is added up , then the total power consumption of the array can be estimated to be around 430 mw . this level of power consumption and associated heat generation may be acceptable for implantation but test data is required for safety evaluations of different tissues . the active elements on the array also may be powered by power induced from sources outside of the body such as through inductive coupling from rf coils , and the like , to permit remote activation , data transmission , etc . when needed or desired from the active elements , without requiring an integrated power source . the electrode array of the invention may be manufactured using one of a number of available fabrication techniques . for example , in accordance with a first technique disclosed by j . rogers at the university of illinois at urbana - champaign , buckled silicon nanoribbons have been shown to provide a stretchable form of single - crystal silicon for high - performance electronics on rubber substrates ( fig1 ) ( see kyang et al . in “ a stretchable form of single - crystal silicon for high - performance electronics on rubber substrates ,” science , vol . 311 , 13 jan . 2006 ). j . rogers has also shown that printed semiconductor nanomaterials may be used to form heterogeneous three - dimensional electronics ( see choi w m , song j , khang d , jiang h , huang y y & amp ; rogers j a , “ biaxially stretchable ‘ wavy ’ silicon nanomembranes ,” nano lett ., ( 2007 ) vol . 7 , pp . 1655 - 1663 .). in the fabrication technique of fig1 , a stretchable single - crystal si device is built on an elastomeric substrate . in the first step ( top ), thin ( thicknesses between 20 and 320 nm ) elements of single - crystal si or complete integrated devices ( transistors , diodes , etc .) are fabricated by conventional lithographic processing , followed by etching of the top si and sio 2 layers of a soi wafer . after these procedures , the ribbon structures are supported by , but not bonded to , the underlying wafer . contacting a prestrained elastomeric substrate ( pdms ) to the ribbons leads to bonding between these materials ( middle ). peeling back the pdms , with the ribbons bonded on its surface , and then releasing the prestrain , causes the pdms to relax back to its unstrained state . this relaxation leads to the spontaneous formation of well - controlled , highly periodic , stretchable wavy structures in the ribbons ( bottom ). those skilled in the art will appreciate that the fabrication techniques disclosed by j . rogers et al . is advantageous in that the devices and circuits are fabricated on traditional silicon using standard soi ( silicon on insulator ) processing techniques and in that very high performance devices , on par with standard silicon devices , are produced . moreover , simple transfer mechanisms yield well - defined wavy silicon structures that are not only flexible , but stretchable as well . however , the development of 2 - dimensional stretchable devices is in an early stage and could be expensive since such devices require one entire wafer of silicon per electrode array , including all of its traditional soi processing steps , plus additional processing steps to make the silicon flexible . another method for fabricating the electrode arrays of the invention is provided by using single - walled nanotubes ( swnts ) ( fig1 ). as described by j . rogers at the university of illinois at urbana - champaign in an article by hong et al ., “ a flexible approach to mobility ,” nature nanotechnology , vol . 2 , april 2007 , such an approach has the potential for very high performance flexible devices as swnts have carrier mobilities of ˜ 10 , 000 cm 2 / vs , which is about 10 × better than silicon . the performance of such single - walled nanotubes is described by zhou et al . in “ band structure , phonon scattering , and the performance limit of single - walled carbon nanotube transistors ,” p . phys . rev . lett ., vol . 95 , 146805 ( 2005 ). in the fabrication technique of fig1 , a flexible electronic device is made by growing randomly orientated single - walled carbon nanotubes on an amorphous sio2 surface ( a ) and then growing dense aligned nanotubes on a quartz crystalline surface ( b ). these steps are followed by the direct transfer of the nanotubes onto flexible substrates by flexible polymer coating ( c ) and removal of the quartz ( d ) to produce flexible , high - performance , high - power electronic devices . however , this technology is still in its early stages , and only single devices have been fabricated to date . lithography techniques are needed to make complex circuits . in accordance with another possible fabrication technique , thin gold films are provided on elastomeric silicone substrates to form stretchable microelectrode arrays ( fig1 ). such an approach is described by s . wagner at princeton in articles by lacour s & amp ; wagner s . entitled “ thin film transistor circuits integrated onto elastomeric substrates for elastically stretchable electronics , electron devices meeting , 2005 . iedm technical digest . ieee international ( 2005 ), pp . 101 - 104 , and by tsay c , lacour s , wagner s & amp ; morrison b . entitled “ architecture , fabrication , and properties of stretchable micro - electrode arrays ,” sensors , 2005 ieee ( 2005 ), pp . 1169 - 1172 . such fabrication techniques are desirable as they have been demonstrated as a viable bio - compatible process for a stretchable micro - electrode . in the fabrication technique of fig1 , an encapsulated electrode is formed on pdms ( fig1 a ). as shown in fig1 b , exposed metal is surrounded by encapsulated metal which is surrounded by encapsulating pdms . the exposed metal forms a contact in the clear encapsulation silicone over the metal pad . however , the resulting active elements are relatively slow and bulky . for example , a thin - film transistor ( tft ) inverter only managed 500 hz operation . finally , in accordance with yet another possible fabrication technique , surface - tree technology by laser annealing ( suftla ) developed by epson corporation may be used ( fig1 ). such technology is described by boyd in “ epson takes major step toward flexible electronics ,” technology newsline , no . 13 , may 2005 . as described in the boyd article , such a fabrication technique is a low cost , large surface area tft process through which complex circuits have been successfully fabricated . however , this fabrication technique produces relatively low performance devices with unpredictable propagation delays . also , the resulting array is flexible , but not stretchable . the implantable arrays described above may be deployed endoscopically or through some other means , such as through surgery ( preferably minimally invasive ). if the array is small , it may be implanted directly as a result of its small footprint . on the other hand , the flexible substrate may be rolled up for introduction and unrolled , unfurled or otherwise expanded once inside the body . on the other hand , the flexible substrate may be placed into the body as part of a vascular stent deployable within the body or as an integral part of a catheter system that is placed within vessels or organs , around peripheral or cranial nerves , and on , in or around other structures of the body . those skilled in the art also will readily appreciate that many additional modifications are possible in the exemplary embodiment without materially departing from the novel teachings and advantages of the invention . for example , a reshaped version of the disclosed electrode arrays may be used to increase the spatial sampling of current depth implantable electrode designs as well . the circuits would be wrapped around the barrel of the electrode body , allowing amplification and multiplexing throughout the length of the depth electrode . this would greatly improve the number of microelectrodes that can be placed in deep brain structures , such as the hippocampus , amygdala , and the anterior nucleus of the thalamus . the array of sensors also may be formed into a hollow or solid cylindrical shape to be implanted into a deep brain structure , wrapped around a nerve bundle or auditory nerve , a blood vessel , a peripheral or cranial nerve , or provided outside or inside a viscus or in or around the heart or eye . on the other hand , the array of electrodes may be formed into a device suitable for cardiac implantation or for recording from and applying stimulation to peripheral or cranial nerves , a spinal cord , a heart , a viscus or other biological target in a patient . the sensor array also may be disposed in a chamber in which biological material removed from the body is placed , and the array or sensors in such an embodiment would record from or monitor activity from the biological materials after removal from the body . the sensor array could be powered via wires , batteries ( single use or rechargeable ), through wireless power ( inductive coupling ), or some combination of those . accordingly , any such modifications are intended to be included within the scope of this invention as defined by the following exemplary claims .
an implantable sensor array incorporates active electronic elements to greatly increase the number of sensors and their density that can be simultaneously recorded and activated . the sensors can be of various configurations and types , for example : optical , chemical , temperature , pressure or other sensors including effectors for applying signals to surrounding tissues . the sensors / effectors are arranged on a flexible and stretchable substrate with incorporated active components that allow the effective size , configuration , number and pattern of sensors / effectors to be dynamically changed , as needed , through a wired or wireless means of communication . active processing allows many channels to be combined either through analog or digital means such that the number of wires exiting the array can be substantially reduced compared to the number of sensors / effectors on the array .