Wireless, battery-free push-pull microsystem for membrane-free neurochemical sampling in freely moving animals

Abstract

Extensive studies in both animals and humans have demonstrated that high molecular weight neurochemicals, such as neuropeptides and other polypeptide neurochemicals, play critical roles in various neurological disorders. Despite many attempts, existing methods are constrained by detecting neuropeptide release in small animal models during behavior tasks, which leaves the molecular mechanisms underlying many neurological and psychological disorders unresolved. Here, we report a wireless, programmable push-pull microsystem for membrane-free neurochemical sampling with cellular spatial resolution in freely moving animals. In vitro studies demonstrate the sampling of various neurochemicals with high recovery (>80%). Open-field tests reveal that the device implantation does not affect the natural behavior of mice. The probe successfully captures the pharmacologically evoked release of neuropeptide Y in freely moving mice. This wireless push-pull microsystem creates opportunities for neuroscientists to understand where, when, and how the release of neuropeptides modulates diverse behavioral outputs of the brain.

On demand nanoliter sampling probe for collection of brain fluid

“…The absence of transient could possibly enable quantifying analytes with slow accumulation dynamics and mass transport, that would otherwise be discarded during the transient period of continuous sampling methods and of which the recovery fraction could be too low for reliable measurement. The absence of membrane on the DoD probe could allow collection of large biomarkers 20 , such as extracellular vesicles 70 . Having a relatively low abundance, they would benefit from the high recovery fraction offered by DoD.…”

“…They also enabled the Kennedy group to improve the temporal resolution of these systems, which was previously limited by Taylor dispersion in the tubing, by coupling the dialysate to a droplet generator at the outlet 21 . Following these advances, new fluidic sampling probes were developed, integrating flow actuation systems 20,22 , droplet generation features 23,24 , and stimulation and sensing electrodes 5 . Our group contributed the advancements through the development of a flexible probe allowing electrostimulation, neural signal recording, and droplet sampling directly at the tip 25,26 .…”

“…The absence of membrane also enables collection of larger biomarkers. Miniaturization techniques have reduced the large footprint shared by both systems, by integrating membranes directly in polyimide 17 and silicon probes 18 and by scaling down the channels 19,20 . They also enabled the Kennedy group to improve the temporal resolution of these systems, which was previously limited by Taylor dispersion in the tubing, by coupling the dialysate to a droplet generator at the outlet 21 .…”

On-Demand Nanoliter Sampling Probe for the Collection of Brain Fluid

“…81 Finally, the absence of a transient regime could improve the quantification of analytes with slow accumulation dynamics, elimination rates, and mass transport, which would otherwise be discarded during the transient period of continuous sampling methods and of which the recovery fraction could be too low for reliable measurement. In addition, the absence of membrane on the DoD probe could allow collection of large biomarkers, 24 such as extracellular vesicles. 82 Having a relatively low abundance, they would benefit from the high recovery fraction offered by DoD.…”

Multiplexed Monitoring of Neurochemicals via Electrografting-Enabled Site-Selective Functionalization of Aptamers on Field-Effect Transistors

“…In past decades, with the advances in neuroscience and micro-/nanofabrication, groundbreaking sensors have been developed to target specific brain regions at different scales. − The main techniques for neurotransmitter monitoring include the following several types: (1) nuclear medicine tomographic imaging, such as positron emission tomography (PET); (2) optical sensing techniques, such as surface-enhanced Raman spectroscopy (SERS), , fluorescence, , chemiluminescence, optical fiber biosensing and colorimetry; (3) electrochemical methods, − like fast-scan cyclic voltammetry (FSCV) − and amperometry; (4) mass spectrometry; ,, and (5) microdialysis sampling (typically coupled with mass spectrometry analysis). − While each of these techniques has its pros and cons, ,, it is still a challenge to build a system that can effectively capture the dynamics of neurotransmitter release with a high temporal resolution, cellular scale spatial resolution, superior sensitivity, and selectivity, not to mention empowering the tools with multiplexed monitoring capabilities. Among these methods, FSCV, microdialysis, and genetically encoded fluorescent sensors are three widely used or emerging techniques for neurotransmitter monitoring .…”