A wireless, implantable optoelectrochemical probe for optogenetic stimulation and dopamine detection
At a Glance
Section titled âAt a Glanceâ| Metadata | Details |
|---|---|
| Publication Date | 2020-08-23 |
| Journal | Microsystems & Nanoengineering |
| Authors | Changbo Liu, Yu Zhao, Xue Cai, Yang Xie, Taoyi Wang |
| Institutions | Beijing Institute of Technology, Tsinghua University |
| Citations | 99 |
| Analysis | Full AI Review Included |
Executive Summary
Section titled âExecutive SummaryâThis analysis focuses on a wirelessly operated, implantable optoelectrochemical microprobe designed for simultaneous optogenetic stimulation and real-time dopamine detection in the deep brain of freely behaving animals.
- Core Value Proposition: Creation of a miniaturized, vertically stacked, thin-film probe enabling closed-loop control and monitoring of neural activities, overcoming the limitations of tethered or bulky devices.
- Device Architecture: The probe integrates InGaN micro-LEDs (for optical stimulation) and PEDOT:PSS-coated diamond films (for electrochemical sensing) on a flexible Cu/PI/Cu substrate.
- Critical Material Role: A 20 ”m thick polycrystalline diamond film serves as an optically transparent (>80%), electrically insulating, and ultrahigh thermal conductivity (>2000 W/m/K) interlayer, ensuring simultaneous, localized function without cross-talk or overheating.
- Thermal Management: The diamond coating significantly improves heat dissipation, restricting the probe surface temperature increase to less than 2 °C (at 3 mA pulsed current), crucial for mitigating tissue damage.
- Sensing Performance: The PEDOT:PSS sensor demonstrated high sensitivity for dopamine detection in vitro, achieving a normalized sensitivity of 200 nA/”M/cm2.
- Wireless Operation: A lightweight (2.0 g total weight), customized circuit module operating at 2.4 GHz enables untethered control and data acquisition, facilitating behavioral studies.
- In Vivo Achievement: Successful demonstration in the ventral tegmental area (VTA) of mice, showing remote control over place preference behavior and recording spontaneous dopamine release spikes.
Technical Specifications
Section titled âTechnical Specificationsâ| Parameter | Value | Unit | Context |
|---|---|---|---|
| Micro-LED Size (Lateral) | 125 x 185 | ”m | InGaN blue emitter |
| Diamond Interlayer Thickness | 20 | ”m | Polycrystalline CVD film |
| PEDOT:PSS Film Thickness | ~100 | nm | Working electrode layer |
| Probe Needle Dimensions | ~360 (W) x ~5 (L) | ”m, mm | Final geometry for deep brain implantation |
| Diamond Thermal Conductivity | >2000 | W/m/K | Interlayer for heat dissipation |
| LED Peak Wavelength | ~470 | nm | Matches ChR2 optical absorption |
| Maximum EQE (Coated LED) | ~10 | % | At 1 mA injection current |
| Temperature Rise (3 mA pulsed) | <2 | °C | With diamond coating (in air) |
| Optical Transmission (Diamond/PEDOT:PSS) | >80 | % | In the visible spectral range |
| Dopamine Detection Limit (DPV) | ~0.1 | ”M | In vitro (HCl solution) |
| Dopamine Sensitivity (CA) | ~0.06 | nA/”M | Linear range 0.1-10 ”M |
| Normalized Sensitivity | 200 | nA/”M/cm2 | Based on 150 ”m x 200 ”m working area |
| Wireless Module Weight | 2.0 | g | Including 0.9 g rechargeable battery |
| Optogenetic Stimulation Frequency | 20 | Hz | In vivo RTPP test |
| Optogenetic Stimulation Current | 1.8 | mA | In vivo RTPP test |
Key Methodologies
Section titled âKey MethodologiesâThe device fabrication relies on heterogeneous integration of thin-film materials using liftoff and transfer printing techniques, followed by precise lithographic patterning.
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Micro-LED Fabrication and Release:
- InGaN blue LEDs (7.1 ”m total thickness) were grown epitaxially on sapphire via MOCVD.
- Lateral dimensions were defined by Inductively Coupled Plasma Reactive Ion Etching (ICP-RIE) using Cl2, BCl3, and Ar gases (4 mTorr pressure, 450 W ICP power).
- Freestanding micro-LEDs were released from sapphire using Laser Liftoff (LLO) via a KrF excimer laser (248 nm) at a power density of ~0.7 J/cm2.
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Diamond Film Preparation:
- Polycrystalline diamond film (~20 ”m thick) was grown on single-crystalline silicon via Chemical Vapor Deposition (CVD).
- The film was patterned using Nd:YVO4 laser milling (1064 nm).
- The silicon substrate was removed via wet etching using a CH3COOH:HNO3:HF (5:5:2 volume ratio) solution to yield freestanding diamond films.
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Microprobe Assembly and Integration:
- A 10 ”m polyimide insulating layer was coated and baked on the flexible Cu/PI/Cu substrate (18 ”m Cu/25 ”m PI/18 ”m Cu).
- Freestanding LEDs and diamond films were transferred sequentially onto the substrate using PDMS stamping with SU-8 photoresist (SU8-3005 and SU8-2002) as adhesive/bonding layers.
- Metal electrodes (Cr/Cu/Au) were sputtered onto the LED and diamond layers.
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PEDOT:PSS Sensor Formation:
- The PEDOT:PSS film (~100 nm) was conformally coated onto the diamond interlayer via spin casting.
- The PEDOT:PSS working area was patterned using Reactive Ion Etching (RIE) with O2 and SF6 gases (90 mTorr pressure, 100 W power).
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Final Probe Shaping and In Vivo Testing:
- The flexible substrate was patterned into a needle shape (~360 ”m wide, ~5 mm long) using UV laser milling.
- In vivo experiments involved implanting the probe into the VTA of DAT-Cre mice expressing ChR2.
- Electrochemical sensing (Chronoamperometry, CA) was performed at a constant forward bias of 0.6 V, using an Ag/AgCl wire (RE) and a stainless-steel screw (CE) implanted in the cortex.
Commercial Applications
Section titled âCommercial ApplicationsâThis technology provides a robust platform for multimodal neural interfaces, leveraging advanced material science for miniaturization and thermal management.
- Neuroscience Research Tools: Development of next-generation, untethered probes for closed-loop optogenetic stimulation and neurochemical monitoring (dopamine, serotonin, glutamate) in freely moving animal models.
- Deep Brain Stimulation (DBS) Systems: Creation of thermally stable, high-density, multifunctional DBS electrodes that integrate optical control and chemical sensing capabilities for precise clinical therapies (e.g., Parkinsonâs disease, depression).
- Advanced Biomedical Implants: Application of the vertically stacked, thin-film architecture for other implantable microelectronic devices requiring high thermal dissipation in biological environments.
- High Thermal Conductivity Substrates: Utilization of CVD diamond films as ultra-efficient heat spreaders for miniaturized, high-power density micro-LEDs and other optoelectronic components in harsh environments.
- Flexible and Stretchable Electronics: Manufacturing of flexible polymer substrates (Cu/PI/Cu) integrated with inorganic semiconductor devices (InGaN micro-LEDs) via transfer printing for wearable or implantable electronics.
- Electrochemical Biosensors: Commercialization of PEDOT:PSS-based thin-film electrodes for highly sensitive, real-time detection of specific biomarkers and neurotransmitters in clinical diagnostics or drug development.