Method and system for reading and stimulating neurons through tissue using light
A neural sensing system includes an interrogator that includes an optical head. The optical head is configured to transmit a light signal. The neural sensing system also includes a microprobe configured to contact tissue. The microprobe includes a transducer configured to receive the light signal and modulate the light signal with neural signal information sensed from the tissue. The microprobe also includes a retroreflector configured to reflect the modulated light signal back to the optical head of the interrogator.
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This application claims the priority benefit as a national stage entry of PCT App. No. PCT/US2018/000140 filed on Aug. 15, 2018, which claims the priority benefit of U.S. Provisional Patent App. No. 62/545,769 filed on Aug. 15, 2017, the entire disclosures of which are incorporated herein by reference.REFERENCE TO GOVERNMENT RIGHTS
This invention was made with government support under ECCS-1310620 awarded by the National Science Foundation. The government has certain rights in the invention.BACKGROUND
Neural sensing refers to the sensing of electrical signals generated by neurons within the brain, and can be used to monitor brain activity and neural responses to various stimuli. Neural sensing can also be used to diagnose various health conditions such as sleep disorders, brain trauma, epilepsy, etc. Traditional neural sensing is performed using a wired array of electrodes placed on the scalp. For example, in electroencephalography (EEG), a non-invasive array of electrodes is positioned on the scalp of a patient and used to detect electrical signals. Other types of neural sensing, such as electrocorticography, are invasive and involve using electrodes that are placed directly on the exposed surface of the brain.SUMMARY
An illustrative neural sensing system includes an interrogator that includes an optical head. The optical head is configured to transmit a light signal. The neural sensing system also includes a microprobe configured to contact tissue. The microprobe includes a transducer configured to receive the light signal and modulate the light signal with neural signal information sensed from the tissue. The microprobe also includes a retroreflector configured to reflect the modulated light signal back to the optical head of the interrogator.
An illustrative method of sensing data includes transmitting, by an optical head of an interrogator, a light signal. The method also includes receiving, by a transducer of a microprobe that is in contact with tissue, the light signal from the optical head. The method also includes modulating, by the transducer, the light signal with neural signal information sensed from the tissue. The method further includes reflecting, by a retroreflector of the microprobe, the modulated light signal back to the optical head of the interrogator.
Other principal features and advantages of the invention will become apparent to those skilled in the art upon review of the following drawings, the detailed description, and the appended claims.
Illustrative embodiments of the invention will hereafter be described with reference to the accompanying drawings.
The most commonly used methods for wired neural sensing include wired microelectrode arrays. Wireless neural sensing methods based on optogenetics are also used in some implementations. Traditional wired microelectrode arrays have significant limitations due to the negative impacts of the microneedles on brain tissue over time. The number of needles is also limited and cannot be easily scaled above thousands. While optogenetic-based approaches have been successful due to their tether-free nature, scaling the read point to above several hundred proves to be challenging due to the high optical (laser) power needed, and the adverse effect (i.e., heat) from such power levels.
The present disclosure relates to a new method which has been developed to read and stimulate neural signals wirelessly using infrared light. This method is highly scalable, and efficient. The energy utilized to transmit a bit of information is very small, and hence the heat dissipation inside the brain tissue remains small even at a high transmission rate. Experiments have demonstrated that tens of thousands of neurons can be read simultaneously, and with little timing delay using the approaches described herein. The large number of neurons, combined with the small timing delay, enable sophisticated neural engineering.
More specifically, described herein are systems and methods for bi-directional low-latency data transmission of light through tissue to record activities of, and/or provide stimulation to, a large number of neurons. The proposed methods and systems can be used in both central nervous system and peripheral nervous system, and for a variety of applications. The proposed system includes two primary components, an interrogator and a plurality of microprobes. The interrogator is an intermediate interface between the outside world (e.g. a computer) and the microprobes. The interrogator can communicate with a large number of microprobes, exceeding hundreds of thousands, with very small timing latency and a high fidelity. The microprobes interface neurons via different modalities including electrical, magnetic, chemical, etc. There are many applications for the proposed system including pain management, direct brain-machine link for quadriplegics, prosthetics, diagnosis, etc. The proposed system will also enable massive brain-machine-brain interface for the first time with a broad range of applications. Specific examples of the electrical interface are described herein.
As discussed in more detail below, the interrogator uses scanning and coherent interference methods to communicate with a specific three-dimensional zone of space at a given time. As a result, the interrogator can collect and transmit data from/to a 4-dimensional spatio-temporal space of interest. This property allows one interrogator to communicate with a large number of microprobes, while tracking their specific locations. The communication with microprobes can be sequential, parallel, or a combination of both sequential and parallel. The proposed systems and methods allow for high-fidelity communication between hundreds of thousands of microprobes and a single interrogator—an ability that is better than the existing technologies by several orders of magnitude. The latency of the whole system is less than the sampling time of each microprobe, which is typically less than a millisecond. In some embodiments, multiple interrogators can be incorporated into the system and used to communicate with different zones of the brain.
The transceiver of the interrogator is configured to convert bi-directional data from the outside world (e.g. a computer) to an all-optical form that is then communicated via the optical head to the microprobes. The transceiver can use existing methods of communication to interface with the outside world, including optical fibers, electrical cables, radio links, or optical free-space links.
The optical head sends/receives light to/from the microprobes. In an illustrative embodiment, the light used can be coherent infrared light at ˜200 THz. Alternatively, a different type of light and/or light frequency may be used. The optical head can be made of conventional bulk optical components, such as lenses and optical scanners, and placed far from the tissue. Also, the optical head can be made from thin and conformal passive and/or active optical components located close to, on, or inside the tissue. For example, optical head can be located under the skull as shown in
The microprobes are located on, or implanted inside the tissue and sense the neural activities via electrical, chemical, magnetic, and other modalities, and transmit the identified signal to the interrogator. The interrogator can also transmit data to the same or a different set of microprobes. Some of these data could be used to control the state of the microprobes, others can modulate neural stimuli, such as electrical and chemical. In the implementation of
As depicted in
In embodiments in which the microprobes are self-powered, the microprobes can include other components such as power harvesting components and electronics. The power harvesting can be optical (i.e. similar to a solar cell), or utilize other modalities such as RF, chemical, and acoustic. The electronics can be used for power regulation, digital signal processing, coding, etc. These components can include many of the existing technologies commonly used for digital communication.
The data transmission from microprobes to the interrogator is based on modulation and retro-reflection. In an illustrative embodiment, the interrogator sends light to microprobes, which is first modulated with the neural data using the transducer, and then returned back via the retroreflector inside the microprobes as shown in
The data transmission from the interrogator to microprobes is based on modulating the incident light beam with the data. The wavelength of this light beam can be the same used for the data transmission from microprobe to interrogator, if common communication protocols are used. However, this approach shares the bandwidth. The wavelength can also be different, such that a photodetector in the microprobe that is only sensitive to a given wavelength converts the modulated light to the data in analog or digital form. The modulator used enables low energy per bit consumption, for example 0.7 fJ/bit.
Other implantable wireless technologies for communicating through tissue include radio frequency (RF) links and acoustic (ultrasound) links. However, the proposed system has several fundamental advantages compared with the RF links. The proposed system enables efficient spatial coding. Optical beams in the tissue optical window (e.g, near infrared (NIR) and short-wave infrared (SWIR)) can stay quite directional within a substantial depth, due to the large isotropic scattering coefficient g=˜0.9 of the tissues. This property allows 4D spatio-temporal communication with microprobes, as detailed herein. Also, methods to improve the beam focusing, such as adaptive optics, can be used to significantly improve the coupling of light into the microprobes.
As compared to other wireless techniques, the proposed system also provides low link loss. The micron size of the wavelength in an optical link allows for much more efficient transmitter and receiver antennas within a small footprint of microprobes implanted at millimeter depths. The optical link not only has a lower link loss, compared to RF, but also has a much better power harvesting efficiency at microprobe dimensions below 100 micrometers (μm). Additionally, the proposed system provides high immunity to external interference. Unlike RF, short wavelength infrared cannot penetrate the skull. While humans are immersed in intense RF sources with digital components (e.g. mobile phones, WiFi, Bluetooth, etc.), infrared sources are mostly natural and do not carry high frequency data components. Therefore, even if light could penetrate inside the skull, it can be easily filtered.
The proposed systems also have several advantages over using ultrasound to communicate with the so-called neural dusts. Compared to ultrasound, the proposed systems enable ultra-high bandwidth. The optical carrier proposed herein is able to carry a massive amount of data compared to an acoustic carrier, due to a much higher optical carrier frequency (tens or hundreds of THz) compared with RF carriers (several GHz to tens of GHz). This is an important property that allows aggregation of all data from/to millions of neurons into a single beam of light that could be carried via an optical fiber through the skull. Also, to enhance the coupling of ultrasound to piezo-electric parts (e.g. inside the neural dust), one has to use resonance coupling. This approach further reduces the acoustic bandwidth.
As compared to other techniques, the proposed system also provides the ability to shrink the microprobes down to dimensions that are smaller than neurons. Infrared light (e.g., NIR and SWIR) can be focused into a few microns in the tissue readily. It has been shown that this property allows microprobes to be smaller than neurons. Many studies suggest large implanted objects lead to stronger tissue reaction and scar cell formation. Ultrasound waves however, cannot be focused to such small dimensions due to their significantly longer wavelengths, and the resulted probes face fundamental physics limitations when scaled to a few tens of microns.
In an illustrative embodiment, microprobes can be delivered into and removed from tissue using a lumbar puncture technique. Lumbar puncture is a routine and safe procedure, done approximately 500,000 times per year in the United Sates, that provides access to cerebrospinal fluid (CSF) in subarachnoid space and connected to brain ventricles. The brain ventricles are lined by an ependymal cell layer. In an illustrative embodiment, microprobes are injected into the CSF via a lumbar puncture procedure, and diffusion or magnetic driven steering is used to direct (i.e., move) the implanted microprobes to the ventricle of interest.
As discussed above, once implanted, magnetic guiding can be used to move the microprobes such that the microprobes penetrate the ependymal cell layer through oscillatory magnetic field forces.
Evaluations have also shown the ability to communicate with microprobes through an intact human skull for imaging applications. Additionally, advanced wavefront correction has demonstrated diffraction-limited micron resolution through an intact skull and dura of rodents. The retroreflector used exhibits a bright, natural ‘guide star’ effect that enhances imaging capabilities, and the technology works with beam sizes that are well above the diffraction limit. Additionally, reducing scattering and absorption of light through skin and skull using optical clearing has been demonstrated and can be used to enhance optical communication deep within the brain.
The ground wire could be connected to the drain or the source of the transistor to make a source-follower or common-source configuration, as depicted in
Described below are two examples for the interrogator design. The first example is based on conventional coherent reflectometry, such as systems used in coherence optical tomography, combined with conventional bulk optical head. This example only provides one-way data transmission from microprobes to the interrogator (i.e. reading neural signals). The second example of interrogator allows bi-directional data transmission, as well as a thin and flexible optical head, similar to what is depicted in
In one embodiment, the interrogator is non-implantable and made with conventional parts.
As also shown in
In another embodiment, the system can utilize an implantable interrogator with a thin optical head and a transceiver system. In such an embodiment, the optical head is implanted under the skull, and communicates with the transceiver system via a single optical fiber (i.e. similar to the embodiment of
In an illustrative embodiment, the light reflected by the retroreflector is modulated by the analog/digital signal and returns back to the transceiver system of
It is noted that the time/wavelength specific to each microprobe is already produced in the previous read cycle, and hence is insensitive to the slow variation of the microprobe location (compared with the KHz read/write speed). Conversely, the modulator in each microprobe is biased in the read mode to only absorb the incident light and hence becomes a photodetector. The generated photocurrent in this photodetector is proportional to the light intensity, and hence directly reproduces the digital write signal coded by the transceiver system. The signal is then decoded by an application specific integrated circuit (ASIC) chip in a digital system, or directly used in an analog system, to produce the stimulation analog signal.
Various system parameters of the proposed neural sensing system include total laser power (PL), tuning range of the laser (ΔL), sweep rate of the laser (fs), diameter of the neural microprobes (dn), read data bandwidth for each neural microprobe (BWn), maximum implant depth (Dn), area of implant coverage (An), average distance between neural microprobes (Ln), total number of surface grating out-couplers (Ngr), total number of neural microprobes (Nn=AnDn/Ln3), number of wavelength channels (Nch), and channel optical bandwidth (BWch).
The total bandwidth of each channel is related to the neural microprobe spacing Ln by: BWch:=2·ln(2)/π·λ02/Ln·nB, where λ0 is the center laser wavelength, and nB is the refractive index of the tissue. The number of wavelength channels is then Nch=ΔL/BWch. The number of bands within the optical head can also be calculated, as their optical pathlength should be larger than the optical pathlength of the implant depth: NB:=An0.5·nWG/Dn·nB, where nWG is the optical index of the waveguide. Finally, the number of depth points resolved is simply depth divided by depth resolution, or Nd=Dn/Ln. The total number of the spatially resolvable points with this method is the product of the three, or Nr=NchNBNd. It follows that the sweeping frequency of the laser is the bandwidth of each spatially resolvable point times the number of the spatial point fs=NrBWn
The sensitivity of the coherent detection based on swept-source method can readily achieve shot-noise limit, which is typically in the order of ˜100 dB. One can also calculate the signal-noise ratio (SNR) from the sensitivity and the optical loss in the link. The main sources of loss considered in experimental models are from the MMI splitter, the waveguide loss, implanted microprobe+brain tissue loss, and the neural microprobe's optical fill-factor—all of which are calculable based on experimental data and other data known in the art.
The difference between the sensitivity and the two-way total insertion loss is the SNR (all in dB). Once the SNR is known one can calculate the channel bitrate in a digital communication, depending on the modulation method. Bit error rate (BER) will also be calculable from the SNR and modulation method. In a purely analog mode, the SNR is simply the SNR of the signal before it is digitized in the transceiver.
The experimental and the calculated return loss obtained in experiments sets the basis for evaluating the performance metrics of the proposed system. Particularly, an evaluation is made of the maximum number of microprobes that can communicate with an interrogator based on the implantation depth, the overall signal SNR, and the sampling rate per microprobe. While digital communication between microprobes and the interrogator is possible, and potentially offers a far better information channel capacity than analog communication, evaluating such systems would strongly depend on the choice of the many digital coding and compression methods. Therefore, a focus of the experiments was on analog communication. For analog communication, the optical beam returning from the microprobe is proportional to the neural signal. The modulated optical signal is attenuated within the tissue before reaching the optical detection system. The electrodes of the microprobe could either sense the voltage inside (intracellular) the neurons or at the vicinity of them (extracellular). The use of an integrated electronic amplifier can be included in the system for detecting the extracellular voltages since they are typically 100 times smaller than their intracellular counterparts. Neglecting the limitation of the lateral beam scan rate, the constraint on the number of microprobes (Nn) originates from the limited power normalized sensitivity bandwidth product (Sn·Bsys) of the homodyne optical interrogator, as follows:
where Sn is the sensitivity of the system divided by the light source power, SNRm is the required signal to noise power ratio, and Bm is the required bandwidth for reliable recording of action potentials. αm is the modulation depth of the optical modulator, LR is the return loss at the depth z and from retroreflectors with diameter d, and Ps is the maximum allowed illumination power, which depends on the depth of implantation z.
This calculation shows that for the experimental data obtained, and the reported sensitivity and bandwidth of the reflectometer, assuming a communication bandwidth of 1 kHz between the interrogator and each microprobe, and a minimum SNRm=9, one interrogator can read more than 100,000 microprobes at a depth exceeding 200 μm. Better interrogator and microprobe technologies can significantly enhance this performance in the future.
The maximum number of neurons that can be recorded simultaneously n can be calculated for a recording bandwidth per neuron Bm and a signal-to-noise ratio SNRm. This model is based on a simple lens solution without adaptive optics. The maximum number of neurons n that can be recorded simultaneously is represented by the relation below in which LR is returned signal strength, Ps is laser power, and αm.
Experiments were conducted to validate of a strong retroreflector return signal through brain tissue. Widely available microsphere products were used to conduct the experiments. These microspheres can be chemically produced in mass numbers with a relatively low cost. The microspheres were half-coated with gold. As shown in the SEM images of
The above-described experiment was also repeated using a flat gold mirror instead of a spherical retroreflector.
Experimental validation of the entire system was also performed. To validate the system, an experiment was performed using a home-built reflectometer (transceiver), and conventional optics such as an objective lens (optical head). The microprobe was made with an optical modulator and a field effect transistor, as described herein, and placed underneath the brain phantom to measure the SNR when recording an action potential (AP) signal using the proposed setup. The optical modulator had an optical bandwidth of 70 nm and a modulation depth of 16% per one volt change of its input voltage.
The incident optical power was ˜1.6 μW and the spot size was ˜45 μm, which results in a maximum intensity of 0.8 mW/mm2 on the tissue, which is within the accepted safe power level of 1 mW/mm2 according to ANSI Z136 standard.
As shown in
Any of the operations described herein can be implemented in the form of computer-readable instructions that are stored on a tangible computer-readable medium and executable by a processing component. For example, the system can utilize a computer that includes a memory which stores the computer-readable instructions, a processor which executes the stored computer-readable instructions, a transceiver that communicates with the neural sensing system and/or other computing devices, and an interface that allows a user to interact with and control the computer.
The word “illustrative” is used herein to mean serving as an example, instance, or illustration. Any aspect or design described herein as “illustrative” is not necessarily to be construed as preferred or advantageous over other aspects or designs. Further, for the purposes of this disclosure and unless otherwise specified, “a” or “an” means “one or more.”
The foregoing description of illustrative embodiments of the invention has been presented for purposes of illustration and of description. It is not intended to be exhaustive or to limit the invention to the precise form disclosed, and modifications and variations are possible in light of the above teachings or may be acquired from practice of the invention. The embodiments were chosen and described in order to explain the principles of the invention and as practical applications of the invention to enable one skilled in the art to utilize the invention in various embodiments and with various modifications as suited to the particular use contemplated. It is intended that the scope of the invention be defined by the claims appended hereto and their equivalents.
1. A neural communication system comprising:
- an interrogator that includes an optical head, wherein the optical head transmits a light signal; and
- a microprobe configured to contact tissue, wherein the microprobe includes:
- a sensor that contacts the tissue;
- a transducer that receives the light signal and neural signal information sensed from the tissue by the sensor, wherein the transducer modulates the light signal with the neural signal information; and
- a self-powered retroreflector configured to reflect the modulated light signal back to the optical head of the interrogator, wherein a diameter of the microprobe is smaller than 100 micrometers.
2. The neural communication system of claim 1, wherein the interrogator further comprises a transceiver configured to communicate with a computing device.
3. The neural communication system of claim 2, wherein the interrogator further comprises a wire that connects the optical head to the transceiver.
4. The neural communication system of claim 3, wherein the wire comprises a fiber optic cable.
5. The neural communication system of claim 2, wherein the transceiver is configured for implantation between skin and a skull of a patient.
6. The neural communication system of claim 2, wherein the transceiver is not implanted within a patient.
7. The neural communication system of claim 1, wherein the optical head is configured for implantation between a dura and a skull of a patient.
8. The neural communication system of claim 1, wherein the optical head is not implanted within a patient.
9. The neural communication system of claim 1, wherein the sensor comprises a microelectrode that contacts the tissue.
10. The neural communication system of claim 1, wherein the microprobe is magnetic such that a magnetic field is able to move the microprobe within the tissue.
11. The neural communication system of claim 1, wherein the transducer of the microprobe is a field effect transistor (FET) in a source-follower configuration or a common source configuration.
12. The neural communication system of claim 1, wherein the interrogator further comprises a reflectometer that is configured to measure power of the modulated light signal.
13. The neural communication system of claim 12, wherein the reflectometer is configured to produce a map of reflectivity versus depth for the microprobe.
14. The neural communication system of claim 1, wherein the interrogator further comprises a two-dimensional scanner configured to direct the light signal to a plurality of tissue locations to scan an area of interest.
15. The neural communication system of claim 1, wherein the microprobe includes a power harvesting system such that the microprobe receives power by way of the light signal.
16. The neural communication system of claim 15, wherein the power harvesting system includes an electroabsorptive modulator.
17. The neural communication system of claim 16, wherein the power harvesting system also includes a field effect transistor.
18. The neural communication system of claim 1, wherein the light signal comprises a read light signal, and wherein the optical head is also configured to transmit a write light signal to stimulate one or more neurons in the tissue.
19. The neural communication system of claim 1, wherein the light signal follows a transmit path from the optical head to the retroflector, and wherein the reflected modulated light signal follows the transmit path in reverse from the retroflector to the optical head.
20. The neural communication system of claim 1, wherein the interrogator is configured to communicate with at least 1000 microprobes that are in contact with the tissue.
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Filed: Aug 15, 2018
Date of Patent: Jan 31, 2023
Patent Publication Number: 20200360721
Assignee: Northwestern University (Evanston, IL)
Inventor: Hooman Mohseni (Wilmette, IL)
Primary Examiner: Brian T Gedeon
Assistant Examiner: Joshua Andrew Schum-Houck
Application Number: 16/638,218
International Classification: A61N 5/06 (20060101);