Application of a sub–0.1-mm 3 implantable mote for in vivo real-time wireless temperature sensing

Chen Shi, Victoria Andino-Pavlovsky, Stephen A. Lee, Tiago Costa, Jeffrey Elloian, Elisa E. Konofagou, Kenneth L. Shepard

Science Advances 2021 · 10.1126/sciadv.abf6312

rodenthealthyemg mepother

Abstract

There has been increasing interest in wireless, miniaturized implantable medical devices for in vivo and in situ physiological monitoring. Here, we present such an implant that uses a conventional ultrasound imager for wireless powering and data communication and acts as a probe for real-time temperature sensing, including the monitoring of body temperature and temperature changes resulting from therapeutic application of ultrasound. The sub-0.1-mm 3 , sub-1-nW device, referred to as a mote, achieves aggressive miniaturization through the monolithic integration of a custom low-power temperature sensor chip with a microscale piezoelectric transducer fabricated on top of the chip. The small displaced volume of these motes allows them to be implanted or injected using minimally invasive techniques with improved biocompatibility. We demonstrate their sensing functionality in vivo for an ultrasound neurostimulation procedure in mice. Our motes have the potential to be adapted to the distributed and localized sensing of other clinically relevant physiological parameters.

Abstract via europepmc.

Speciesmouse

Subjectsnot reported animals

Sessions per subjectnot reported

Randomisednot reported

Blindingnot reported

Sham / controlnone

Auditory controlnot reported

Readout timingonline

Anaesthesiaanaesthetised

Readoutsemg mep, other — EMG (needle electrode) of gastrocnemius; implanted ultrasonic mote temperature sensing at the nerve

Direction of effectexcitatoryFUS at the sciatic nerve induced gastrocnemius muscle contractions confirmed by EMG, with higher intensity giving larger EMG peaks; main finding is mote-measured heating up to about 0.77 C at 1745.83 mW/cm2.

Adverse eventsnot reportedTemperature rise at the nerve measured with implanted motes (up to about 0.77 C at 1745.83 mW/cm2); no tissue safety assessment in this study.

Exposures

Exposure 1: FUS of sciatic nerve, mouse hindlimb

Target: sciatic nerve — “sciatic nerves inside the lower hindlimb”
Device: Sonic Concepts · SonicConcepts (Bothell, WA) · SU-107 ✓

Pulse timing
Waveform	pulsed
Fundamental frequency (kHz)	3,570	✓✓✓
Pulse duration (ms)	1	✓✓✓⚑
Pulse repetition frequency (Hz)	10	✓✓✓
Duty cycle (%)	not reportedpulse duration × PRF gives 1%
Sonication duration (s)	not reported	⚑

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 estimate	not reported
In-situ pressure (kPa)	not reported
In-situ Isppa (W/cm²)	not reported
In-situ Ispta (W/cm²)	not reported
Ispta, domain unspecified (W/cm²)	0.958, 1.35, 1.61, 1.75swept	✓✓✓⚑

Protocol, in the paper’s words

Ultrasonic pulse trains of 1-ms pulse duration and 10-Hz PRF applied to the sciatic nerve through a water-filled coupling cone at four Ispta levels (957.99, 1348.02, 1608.21, 1745.83 mW/cm2); train duration and duty cycle not stated.

Flags from extraction

exposures[0].unspecified_domain.ispta_w_cm2 — Four intensities given in mW/cm2 and converted to W/cm2; recorded as [min, max] of the four listed; domain not stated
exposures[0].timing.sonication_duration_s — Train duration and duty cycle not stated for the sciatic FUS
n_subjects — Number of mice used not stated; motes also used in mice and tissue for non-stimulation sensing experiments (L12-3v imaging probe, 8.3 MHz, not neuromodulation, not recorded as an exposure)
exposures[0].timing.pulse_duration_ms — The pulse-train sentence is split across a page break in the extracted text; quoted the continuation