JACS: nanoparticle based "click SERS" for assisted multi fluid biopsy and accurate cell imaging

In clinical application, the diagnosis and treatment information provided by a single biomarker is often insufficient, and multiple biomarkers can improve the clinical practical value Among the current optical analysis methods, colorimetry, fluorescence and SERS can provide multiple biomarkers Compared with other methods, SERS has the advantages of multiplicity, high light stability and high sensitivity, and has great application potential in tumor imaging However, its disadvantages can not be ignored: the size of nanoparticles (NPS) used to enhance substrate scattering is usually designed to be larger than the tumor cell membrane receptor, resulting in inaccurate cell imaging; the gravity of metal matrix will cause non-specific adsorption, resulting in false-positive results; in the long-term cell culture process, the endocytosis of NPs has a serious adverse impact on the accuracy Recently, Professor Shen Aiguo and his collaborators of Wuhan University have developed a new reading technology based on NPs Raman spectrum splicing This is not a single specific reaction, but a reaction by effectively connecting small "modular units", which are temporarily named "click SERS" because of their similarity with click chemistry Relevant articles were published in J am Chem SOC (DOI: 10.1021 / JACS 8b04892) under the title of "spreading nanoparticles based" click "SERS could aid multiple liquid biology and accurate cellular imaging" Clicksers can be driven by energy from biological, chemical and physical sources Under the high thermal drive, the nanoparticles with SERS activity have a single and narrow peak emission (1-2 nm) in the Raman silencing region (1800-2600 cm-1), which makes NPs suitable as a "SERS unit" in clicksers The plasma coupling between particles makes the three bond labeled SERS unit have the characteristics of controllable and artificial splicing, which is very likely to be applied to the dynamic combined signal output of single emission peak (Figure 1) Different from the traditional read-out method of "one target one data correspondence", click SERS depends on the number and position of the target rather than the intensity of combined emission, which makes it have the advantages of intuitionistic, predictable and unique recognition (image source: J am Chem SOC.) the authors then performed multiple fluid biopsies, including a statistical analysis of DNA hybridization reactions and results In order to verify the feasibility of practical application of the probe, the authors synthesized a series of SERS reporter molecules with three bonds, highly different scattering cross sections and distinct peaks in the range of 1800-2600 cm-1, further used AuNPs with a diameter of 20 nm as the enhancement matrix, and connected with polyadenine DNA as the capture probe to detect 10 DNA targets (Figure 2A ) If the measured spectrum exactly matches the expected result, it will be displayed in yellow, otherwise it will be displayed in white to form a barcode (Figure 2f) Then the author combines barcode with QR code (Figure 2e), which can be used for multi-target response and rapid analysis The above data show that the system has potential in rapid clinical diagnosis (photo source: J am Chem SOC.) in order to eliminate the false-positive results of the system in endocytosis, the author then conducted a double exposure experiment (Figure 4) The target probe labeled with ope1 showed a strong Raman signal at 2152cm-1, describing the general morphology of the cell When 4-mercaptobenzonitrile (MBN) was used as the gating probe, the Raman signal appeared at 2227 cm-1, indicating that click SERS probe still existed on the cell surface after incubation The yellow area is the click spectrum composed of the overlapped parts of 2152cm-1 and 2227cm-1, highlighting the true position of the receptor The red and green areas are the false positive results caused by gravity (Figure 4a, figure 4B and 4C are the corresponding SERS spectra) The above data show that click SERS achieves accurate cell imaging at dual wavelengths Click SERS proves that multiple single band Raman scattering may be a real and reliable optical analysis method in biomedicine (photo source: J am Chem SOC.) in a word, the author introduces a new concept of readout - "click SERS spectrum" through dynamic spectrum splicing This spectrum has great coding ability and can be used for high-throughput identification of a variety of biomarkers and accurate cell imaging With the development of multi fluid biopsy technology, click SERS may play an important role in the accurate diagnosis and treatment of cancer.