4.8 Article

Monitoring Amyloidogenesis with a 3D Deep-Learning-Guided Biolaser Imaging Array

Journal

NANO LETTERS
Volume -, Issue -, Pages -

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/acs.nanolett.2c03148

Keywords

biolaser; amyloidogenesis; droplet resonator; deep learning; drug screening

Funding

  1. A * STAR Singapore [A2084c0063]
  2. Institute for Digital Molecular Analytics and Science under the Research Centres of Excellence scheme of MOE
  3. Ministry of Education [MOE-T2EP50120-0001]

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The study developed a peptide-encapsulated droplet microlaser to monitor the amyloidogenesis process and evaluate the effectiveness of anti-amyloid drugs. By extracting information from laser images, the progression of the amyloidogenesis process can be monitored using arrays of laser images from microdroplets. The results demonstrate the great potential of peptide microlasers for protein misfolding studies and high-throughput imaging of cavity biosensing.
Amyloidogenesis is a critical hallmark for many neurodegenerative diseases and drug screening; however, identify-ing intermediate states of protein aggregates at an earlier stage remains challenging. Herein, we developed a peptide-encapsulated droplet microlaser to monitor the amyloidogenesis process and evaluate the efficacy of anti-amyloid drugs. The lasing wavelength changes accordingly with the amyloid peptide folding behaviors and nanostructure conformations in the droplet resonator. A 3D deep-learning strategy was developed to directly image minute spectral shifts through a far-field camera. By extracting 1D color information and 2D features from the laser images, the progression of the amyloidogenesis process could be monitored using arrays of laser images from microdroplets. The training set, validation set, and test set of the multimodal learning model achieved outstanding classification accuracies of over 95%. This study shows the great potential of deep-learning-empowered peptide microlaser yields for protein misfolding studies and paves the way for new possibilities for high-throughput imaging of cavity biosensing.

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