Implantable Stimulator-Transponder




[07-OCT-23] Our Implantable Stimulator-Transponders (ISTs, A3041) are implantable, wireless devices that provide pulsed electrical stimulation or pulsed electrical power for an implantable lamp, such as our Implantable Light-Emitting Diodes (ILEDs). They each contain an embedded Each IST contains its own OSR8 microprocessor capable or running user-provided programs. They are designed for long-term experiments that require intermittent stimulation. The IST provides stimulation, acknowledgement, battery monitoring, synchronizing signal, and user-progrsam upload all by radio control. It receives commands through its loop antenna using its on-board crystal radio. It transmits signals through the same antenna using our Subcutaneous Transmitter (SCTs) telemetry protocol.

Figure: The Implantable Stimulator-Transponder (A3041A) with Test Lamp. Volume when encapsulated 0.70 ml, encapsulated mass 1.6 g, encapsulated dimensions 11 mm × 11 mm × 7 mm. In this example, the stimulus leads are 45-mm long, with total resistance 56 Ω. The pins at the ends of the leads mate with sockets on an implantable lamp.

Our SCTs provide wireless, long-term, continuous monitoring of biopotentials to accompany intermittent stimulation. When we have both a sensor and a stimulator implanted in an animal, we can generate stimuli in response to sensor events. This real-time response to sensor data with a stimulus is what we call closed-loop control. Watching for seizure onset in EEG, and responding to seizure onset with twenty seconds of electrical pulses applied to the brain, is an example of a closed-loop system.

Figure: Fiber-Coupled LED (FCLED) For Depth Illumination in Mice. Fiber diameter 270 μm, length 4±0.3 mm. The tip emits 2.8 mW at 10 mA forward current.

For electrical stimulation, the IST drives a bipolar stimulation electrode with constant-current pulses. For optical stimulation, it drives one of our implantable lamps with pulses of current. Our Surface-Mount Light-Emitting Diodes (SMLEDs) come in red, green, and blue. These are designed to be fastened to the surface of an organ and illuminate the tissue within. Our Fiber-Coupled Light-Emitting Diodes (FCLEDs) are designed to be mounted to the skull for illumination of deeper brain tissue.


[07-OCT-23] At the moment, the only way to command the IST is with a Command Transmitter (A3029C) connected to a LWDAQ Driver (A2071E). We describe how to connect these devices, along with an Octal Data Receiver (A3027), in our setup instructions for earlier versions of the stimulator, which you will find at Set-Up. We set up TCPIP communication between our data acquisition computer and the LWDAQ Driver. We run the LWDAQ Software on our computer. We use the program's Stimulator Tool to transmit commands to the IST and we use its Receiver Instrument to receiver signals from the IST. We must use Stimulator Tool V3.9+, available in LWDAQ 10.6.2+.

Figure: Today's IST and SCT Command and Recording System. Soon to be replaced by the Telemetry Control Box (TCB-B16).

The Telemetry Control Box (TCB-B16) will replace the A3029C, A3027E, and A2071E. The TCB-B16 needs only one Power over Ethernet (PoE) connection for power and communication. It provides sixteen coaxial antennas that receiver telemetry signals and transmit commands to ISTs, or indeed any other of our implants with crystal radio receivers. The TCB-B16 should be available in November 2022. With the TCB-B16, set-up is simpler: we put antennas wherever we need reception or transmission, and we can use any antenna alternately for reception and transmission. The TCB receives its power from the PoE connection, and all communication with the TCB takes place over the same PoE cable. The same LWDAQ Software with its Stimulator Tool operates the TCB using the same interface as for the older A3029C, A3027E, and A2071E system.

With the Stimulator Tool, we define a stimulus by specifying a number of pulses, the length of each pulse, and the period of the pulses. One minute of 10-ms pulses at 10 Hz would be 600 pulses, each 10 ms, with period 100 ms. We specify the current of the pulses with another number between zero and fifteen. Consult the IST circuit manual for how these numbers relate to the current and voltage limits of the stimulus. We specify if the stimulus is to be random or regular. In a random stimulus, the pulses can occur anywhere within each period window, at random. We find that random stimuli do not invoke optogenetic response, while regular stimuli do. Random stimuli have the potential to act as a control stimulus.

Figure: Connections to an Implantable Stimulator and Local Field Potential Sensor for Optogenetic Experiment. We have S+ and S− from an Implantable Stimulator-Transponder (IST) connected to a Fiber-Coupled Light-Emitting Diode (FCLED). We have X+ and X− from a subcutaneous transmitter (SCT) connected to a depth electrode and a skull screw.

The Stimulator Tool allows us to request acknowledgements for each command, in which case the Receiver Instrument, i it is running, will pick out the acknowledgement and the Stimulator Tool will confirm that the command was received. The Stimulator Tool will also transmit a general identification request that all ISTs in range will respond to by transmitting their identity numbers. The Stimulator Tool will transmit a battery measurement requests as well, and present the results of the measurement.

Each IST contains its own OSR8 microprocessor running a main program, but also capable of running code provided by its user. The Stimulator Tool also allows us to assemble, upload, and run programs on an IST. These programs are written in the OSR8 assembly language. The Stimulator Tool manual provides example code. Editing, testing, uploading and running user programs is simple with the Stimulator Tool's built-in Transmit Panel. The A3041 stimulator provides 2 KByte of volatile user-program memory. When the A3041 goes to sleep, it forgets its user program, so we must upload it again as part of our experimental procedure. Future ISTs will provide non-volatile user program memory so that we can upload complex programs and have them be available as soon as the IST wakes up.


[27-JUL-22] We implant the IST subcutaneously, and tunnel its leads to the stimulus location. Most often, we will equip the leads with pins that will plug into sockets on a bipolar electrical stimulus electrode, or plug into an implantable light-emitting diode (ILED).

Video: Optogenetic Response. An Implantable Stimulator-Transponder (IST) and a Fiber-Coupled Light-Emitting Diode (FCLED) provoke circling in a mouse with 1-ms pulses of blue light at 10 Hz for 90 s. Pulsed lamp current is 15 mA and optical power at fiber tip is 15 mW. Courtesy Alice Hashemi (OSI) and Robert Wykes (ION/UCL)

If we are performing an optogenetic experiment with an ILED, we may also be recording EEG or some other biometric signal with an SCT implanted seprately in the same animal. If so, we must make sure the ILED drive signal does not corrupt the sensor signal with what we call lamp artifact. We plug the stimulator pins into the ILED, cover them with a thin layer of dental cement or vetbond, lower the ILED into position, and cover thoroughly with dental cement to secure the ILED and further insulate its stimulus pins from the rest of the body. With care, we can provide insulation adequate to reduce the lamp artifact to below a few microvolts. If we are not careful, the lamp artifact can tens of microvolts. For an explanation of how lamp artifact arises even when we have separate implants, see Sources of Lamp Artifact. For video and EEG recordings made with an IST and SCT during optogenetic response, see Examples of Optogenetic Response


[31-AUG-23] Development of the IST began in 2012 with the development of an Implantable Sensor with Lamp (ISL) for use in rats. Work on the ISL for rats was funded by the Wellcome Trust via Dimitri Kullmann at the Institute of Neurology (ION) at University College London (UCL). We collaborated with Dimitri Kullmann, Robert Wykes, and Matthew Walker, all of ION/UCL. The Implantable Sensor with Lamp (A3030) was a failure in that we were unable to isolate the sensor input from the lamp voltage. When implanted in an animal, we found the sensor signal was usually corrupted by lamp artifact of at least 1 mVpp. In 2019 we began work on a mouse-sized implantable stimulator-transponder (IST) with funding from the Fitzgerald Laboratory at UCL and OSI's research budget. This IST was the first device to include only a stimulator. In 2020 we began work on a mouse-sized ISL with the support of a Small Business Innovation Research (SBIR) Phase I grant from the National Institute of Health (NIH), in collaboration with the Schaffer Laboratory at Cornell University. The Implantable Sensor with Lamp (A3037) was a success in that it was small enough to implant in a mouse, and reduced the lamp artifact to less than 100 μVpp. Nevertheless, when it came to initiating optogenetic response and recording electroencephalogram (EEG) in mice, we used IST in conjunction with SCTs, not the ISL.

In 2022 our application for Phase II funding from the NIH was declined for the second time. The reviewers saw no particular need for the stimulator and sensor to be combined in one device, and we agree with them. The animal trials we conducted in 2021 at ION/UCL and Cornell University demonstrated that 1-ms, 15-mW pulses of blue light delivered by an FCLED at 10 Hz were sufficient to invoke optogenetic response. Our expectation had been that 10-ms pulses would be required. With the stimulus power requirement ten times lower than we expected, we were able to switch from lithium-ion batteries as a power source to lithium primary cells. The latter have three times the charge capacity per unit volume as the former, allowing us to triple our operating life. In 2022, we used OSI's research budget to design and test the Implantable Stimulator-Transponder (A3041). The A3041, along with the A3036IL implantable lamps, are the final result of our ten years of work on implantable stimulators. The A3041 is small, long-lasting, corrosion-resistant, and provides both electrical and optogenetic stimulation. We have abandoned our plans to make a combined sensor and stimulator, but you will find our old ISL page here.

In the summer of 2023 we assembled a set of A3041AV1 and worked on discovering bugs in their firmware and hardware. We found that the CR1025 battery is inadequate to power up the A3041AV1 assembly after a few weeks of implantation. We must use the larger CR1225 and CR1620 batteries. We discovered several other problems with the circuit, such as its inability to turn off after being asked to transmit a synchronizing signal of too high a sample rate. We solved all these problems and added to the A3041 the ability to receive and run user-programs. We reduced the hibernation current of the device to less than 1 μA and its sleep current to less than 5 μA. The result is what we believe to be a versatile and long-lasting implantable stimulator for intermittent stimulation experiments.

Examples of Optogenetic Response: Examples of EEG recordings with synchronous video showing optogenetic response.

Implantable Stimulator-Transponder (A3041): A non-rechargeable, long-life, implantable stimulator that acknowledges command reception, provides synchronizing signal, and monitors its battery voltage.

Implantable Light-Emitting Diodes (ILEDs): Implantable lamps for use with implantable stimulators.

Telemetry Manual: Description of the telemetry system in which the stimlators operate.

Telemetry Control Box (TCB-B16): A sixteen-way telemetry receiver, activity monitor, location estimator, and command transmitter, available late 2024.

Command Transmitter (A3029): A 910-MHz transmitter for use with ISTs, will be replaced by the TCB-B16 in late 2024.

Stimulator Tool: The program that controls ISTs, available in the LWDAQ Tool Menu. Initiates stimuli, turns on data and synchronizing transmission, monitors acknowledgements, checks battery voltages.

OSR8: Open-Source Reconfigurable Eight-Bit Microprocessor.

Forum: Forum for optogenetics and telemetry users.

Parts and Prices: A list of devices and their prices.

The ISL Blog: The development logbook we kept during our initial work on the implantable sensor with lamp.