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Real-time simultaneous visualization of lactate and proton dynamics using a 6-μm-pitch CMOS multichemical image

Hideo Doi1, Hayato Muraguchi1, Tomoko Horio1

  • 1Electrical and Electronic Information Engineering, Toyohashi University of Technology, 1-1 Hibarigaoka, Tempakucho, Toyohashi, Aichi, 441-8122, Japan.

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|November 10, 2024
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Summary

This study introduces a novel CMOS sensor for simultaneous, label-free imaging of lactate and proton (H+) dynamics in the brain. This bioimaging tool offers subcellular resolution for studying brain function and pathology.

Keywords:
BioimagingLactatePotentiometric sensor arrayProtonRedoxSimultaneous measurement

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Area of Science:

  • Neuroscience
  • Biomedical Engineering
  • Analytical Chemistry

Background:

  • Understanding extracellular chemical signaling is vital for brain function and pathology.
  • Current methods for analyzing these molecules often lack spatial or temporal resolution.
  • Label-free detection is desirable for preserving biological system integrity.

Purpose of the Study:

  • To develop a CMOS-based multichemical image sensor for simultaneous, label-free detection and imaging of lactate and proton (H+) dynamics.
  • To achieve subcellular resolution in real-time imaging of these key extracellular molecules.
  • To provide a novel bioimaging tool for studying extracellular microenvironments.

Main Methods:

  • Fabrication of a 6-μm-pitch CMOS potentiometric sensor array with gold electrode patterns.
  • Utilized semiconductor lithography for sensor construction.
  • Lactate detection via potentiometry using lactate oxidase and horseradish peroxidase enzyme-based redox reactions.

Main Results:

  • Achieved a pH sensitivity of 65 mV and a lactate detection limit of 1 μM with good selectivity.
  • Successfully obtained concurrent diffusion images of lactate and proton (H+) distributions.
  • Demonstrated simultaneous real-time imaging of both analytes with subcellular resolution.

Conclusions:

  • The developed multichemical image sensor enables simultaneous, label-free visualization of lactate and proton (H+) dynamics.
  • The sensor provides high sensitivity, selectivity, and subcellular resolution for bioimaging applications.
  • This novel device holds potential for effective application in extracellular microenvironments of tissue and cell samples.