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Optoacoustic Neuromodulator by In Situ Photothermal Curing of Polydimethylsiloxane

Guo Chen, Michael Marar, Deming Li, Zhuqin Xu, Biwen Gao, Meng Zhang, Wai Yuen Cheng, Feiyuan Yu, Carolyn Marar, Ji‐Xin Cheng, Chen Yang

Advanced Optical Materials 2026, 14 · 10.1002/adom.202503610

in vitro cellhealthycellular imaging

Abstract

Precise neural modulation is an important tool in neuroscience research for intervening in specific neural pathways. Photoacoustic is an emerging photonics technology enabling high precision non‐genetic neural stimulation in vitro and in vivo. Fiber‐based and film‐based optoacoustic emitters have demonstrated their capability in fundamental studies of how neurons respond to mechanical stimuli at the single‐cell level, as well as in brain stimulation in vivo. Here, we report a new and general method to fabricate optoacoustic emitters through an in situ photothermal curing process of PDMS (Polydimethylsiloxane) on different platforms, including the tip of tapered fibers with high precision, and flat substrates with programmed patterns. Candle soot‐based tapered fiber optoacoustic emitter (CS‐TFOE) prepared through this new method generated a highly localized ultrasound field and enabled efficient and precise neuromodulation. We designed an integrated and compact photoacoustic neuromodulation system incorporating the FOE, a nanosecond pulsed laser for photoacoustic generation, and a function generator for synchronization. We have shown that the system can be easily integrated with standard neuroscience recording methods, such as Ca 2+ imaging, and achieves effective neuromodulation in vitro.

Abstract via crossref.

Speciesrat (Sprague-Dawley), primary cortical neuron culture
Subjects10, 20, 10swept cultures
Sessions per subjectnot applicable
Randomisednot applicable
Blindingnot applicable
Sham / controlinactive transducer
Auditory controlnot reported
Readout timingonline
Anaesthesianot applicable
Readoutscellular imagingCalcium fluorescence imaging (GCaMP6f, ΔF/F0) of cortical neurons
Direction of effectexcitatoryPhotoacoustic stimulation via the CS-TFOE produced dose-dependent calcium activation (ΔF/F0 increases) in targeted single neurons; a 3 ms burst produced transient activation (~65% ΔF/F0), a 4.5 ms burst caused overactivation (250% ΔF/F0) with failure to return to baseline, and a 1 ms burst produced no activation.
Adverse eventsnot applicableA 4.5 ms laser burst duration caused overactivation of neurons (250% ΔF/F0) with an inability to return to baseline after 20 s, indicating possible neuronal damage; a 3 ms burst produced transient, reversible activation without apparent damage over the repeated-stimulation test window.

Exposures

Exposure 1: Photoacoustic (CS-TFOE) stimulation of single GCaMP6f-labeled cortical neurons in vitro

Target: cultured neurons — “GCaMP6f labelled rat cortical neurons in vitro
Device: custom-built · Candle Soot-based Tapered Fiber Optoacoustic Emitter (CS-TFOE)

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)30,000✓✓
Pulse duration (ms)not reported
Pulse repetition frequency (Hz)3,300✓✓
Duty cycle (%)not reported
Sonication duration (s)0.0045, 0.003, 0.001swept✓✓
Pressure and intensity, by domain
Free-field pressure (kPa)not reported
Free-field Isppa (W/cm²)not reported
Free-field Ispta (W/cm²)not reported
In-situ estimatenot applicable
In-situ pressure (kPa)not applicable
In-situ Isppa (W/cm²)not applicable
In-situ Ispta (W/cm²)not applicable
Protocol, in the paper’s words

A CS-TFOE was positioned within 20 µm above a targeted neuron using a micromanipulator, and it was operated under a 1030 nm laser with 3 ns pulse width at a repetition rate of 3.3 kHz, and a power of 41 mW over a duration of 3 ms. Neural responses under different laser burst durations of 4.5, 3, and 1 ms were recorded under the same averaged laser power of 41 mW. Repeated stimulation was performed over the course of two minutes with a time interval of 40 s between trials.

Consistency checks: f0 out of range.

Flags from extraction

  • exposures[0].fundamental_frequency_khzThe 30 MHz central frequency was measured during separate device characterisation (optical detection of the CS-TFOE signal), not necessarily re-measured during the in vitro neuromodulation experiment itself; assumed representative of the same device/laser conditions.
  • n_subjectsCounts (N=10, N=20, N=10) are per burst-duration condition in the dose-response calcium-imaging experiment; the paper does not state whether these are distinct neurons across conditions or state a combined total, so group sizes are listed rather than summed.
  • exposures[0].sham_typeSham/control here is a 'laser-only' control (bare fibre, no photoacoustic coating) and a 'photothermal-only' control (CW laser, no nanosecond pulsing); closest listed category is inactive_transducer (no ultrasound generated) though the mechanism differs from a conventional TUS sham.