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Concentration Determination at a Countable Molecular Level in Nanofluidics by Solvent-Enhanced Photothermal Optical
Yoshiyuki Tsuyama1, Kazuma Mawatari2
1Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, 7-3-1, Hongo, Bunkyo, Tokyo 113-8656, Japan.
Analytical Chemistry
|October 20, 2020
Summary
We enhanced photothermal optical diffraction (POD) for nanofluidic devices, enabling sensitive detection of nonfluorescent molecules. This method achieves single-digit molecule detection, crucial for ultrasmall sample volumes in chemical and biological analyses.
Area of Science:
- Analytical Chemistry
- Nanotechnology
- Spectroscopy
Background:
- Nanofluidic devices offer precise single-molecule/nanoparticle analysis but require sensitive detection methods due to ultrasmall sample volumes (fL-aL).
- Photothermal spectroscopy (PTS) is a promising technique, and photothermal optical diffraction (POD) was previously developed for nanofluidics.
- Existing POD methods had limitations, with detectable concentrations in the μM range (10^2–10^4 molecules), necessitating performance improvements.
Purpose of the Study:
- To enhance the sensitivity and detection range of photothermal optical diffraction (POD) for nanofluidic applications.
- To enable the concentration determination of nonfluorescent molecules at a countable molecular level within nanochannels.
- To elucidate the relationship between POD signals and solvent properties for optimization.
Main Methods:
- Solvent-enhanced photothermal optical diffraction (POD) was implemented with optimized experimental conditions.
- Thermal simulations and theoretical calculations were used to estimate diffraction and photothermal factors of solvent enhancement.
- Experimental results were compared with theoretical predictions to validate the enhancement effect.
Main Results:
- The study demonstrated solvent-enhanced POD, significantly improving detection performance for nonfluorescent molecules in nanochannels.
- A clear relationship between POD signal intensity and the thermal/optical properties of solvents was established.
- The optimized method achieved a limit of detection of 75 nM, corresponding to an average of 10 molecules in a 0.23 fL detection volume.
Conclusions:
- Solvent-enhanced POD successfully improves the sensitivity of molecular detection in nanofluidic devices.
- The method allows for concentration determination of nonfluorescent molecules at the single-digit molecule level.
- This advancement holds significant potential for diverse chemical and biological analyses leveraging nanofluidics.

