Abstract

Recently, preparation and screening of compound libraries remain one of the most challenging tasks in drug discovery, biomarker detection, and biomolecular profiling processes. So far, several distinct encoding/decoding methods such as chemical encoding, graphical encoding, and optical encoding have been reported to identify those libraries. In this paper, a simple and efficient surface-enhanced Raman spectroscopic (SERS) barcoding method using highly sensitive SERS nanoparticles (SERS ID) is presented. The 44 kinds of SERS IDs were able to generate simple codes and could possibly generate more than one million kinds of codes by incorporating combinations of different SERS IDs. The barcoding method exhibited high stability and reliability under bioassay conditions. The SERS ID encoding based screening platform can identify the peptide ligand on the bead and also quantify its binding affinity for specific protein. We believe that our SERS barcoding technology is a promising method in the screening of one-bead-one-compound (OBOC) libraries for drug discovery.

Highlights

  • Tags and tag synthesis reactions that may cause artifacts against the library synthesis

  • Optical encodings commonly rely on specific color or spectroscopic information of light emitted from several optical materials such as fluorescence dyes[7,23,28,29], quantum dots (QDs)[12,20], photonic structures[14,30], and Raman tags[9,10,11,31]

  • Six colors at six different intensities would yield around 40,000 different codes, but in practice, overlap between the different intensities is a major limitation[8]. These graphical and optical encoding methods present several drawbacks: (i) they lack massive parallel coding to produce “pre-encoded microcarriers”; (ii) encoded microcarriers, which initially present a non-biocompatible cross-linked polymer environment, must be functionalized for further conjugation of ligands; (iii) a sequential attachment of fully synthesized bio-ligands is required; and (iv) the decoding process is not suitable for automation due to complex codes, which could lead to an ambiguous interpretation, and due to the fact that an orientation of the encoded microcarriers must be determined before the decoding process[8,32,33]

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Summary

Results and Discussion

The TG beads were identified from the SERS barcodes to the corresponding peptide sequences or biotin and the 4 kinds of SERS barcodes from representative TG beads were shown in Fig. 5c and Figure S10. Low fluorescence signals were detected for weak binding peptide and for the control peptide group, indicating high specificity and a low level of non-specific protein binding These findings suggest that the SERS barcoding method can be used to screen biomolecules and has great potential for multiplexed bioassays. The SERS barcoding technology offers a great promise in the field for screening OBOC libraries and in the applications for drug discovery

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