Limits...
Rational design of a chalcogenopyrylium-based surface-enhanced resonance Raman scattering nanoprobe with attomolar sensitivity.

Harmsen S, Bedics MA, Wall MA, Huang R, Detty MR, Kircher MF - Nat Commun (2015)

Bottom Line: Raman imaging has surfaced as a promising optical modality that offers both.Here we report the design and synthesis of a group of near-infrared absorbing 2-thienyl-substituted chalcogenopyrylium dyes tailored to have high affinity for gold.When adsorbed onto gold nanoparticles, these dyes produce biocompatible SERRS nanoprobes with attomolar limits of detection amenable to ultrasensitive in vivo multiplexed tumour and disease marker detection.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, USA.

ABSTRACT
High sensitivity and specificity are two desirable features in biomedical imaging. Raman imaging has surfaced as a promising optical modality that offers both. Here we report the design and synthesis of a group of near-infrared absorbing 2-thienyl-substituted chalcogenopyrylium dyes tailored to have high affinity for gold. When adsorbed onto gold nanoparticles, these dyes produce biocompatible SERRS nanoprobes with attomolar limits of detection amenable to ultrasensitive in vivo multiplexed tumour and disease marker detection.

No MeSH data available.


Related in: MedlinePlus

The SERRS-intensity as a function of dye affinity for the gold surface(A) Molecular structures of the adsorbed CP-dyes (1–3) arranged by increased number of 2-thienyl substituents (Ph, phenyl). (B) SERRS spectra of the CP-based SERRS-nanoprobes. The SERRS spectra were baseline corrected to allow proper comparison. (For the non-baseline corrected spectra see Supplementary Figure 3). Inset: intensity of the 1600 cm−1 peak (n=3; error bars represent standard deviations, *P<0.05; an unpaired Student’s t-test was performed). C) Colloidal stability of the CP-based SERRS-nanoprobes as determined by LSPR measurements (n=3; error bars represent standard deviations; See also Supplementary Figure 2; Supplementary Table 1).
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4372816&req=5

Figure 3: The SERRS-intensity as a function of dye affinity for the gold surface(A) Molecular structures of the adsorbed CP-dyes (1–3) arranged by increased number of 2-thienyl substituents (Ph, phenyl). (B) SERRS spectra of the CP-based SERRS-nanoprobes. The SERRS spectra were baseline corrected to allow proper comparison. (For the non-baseline corrected spectra see Supplementary Figure 3). Inset: intensity of the 1600 cm−1 peak (n=3; error bars represent standard deviations, *P<0.05; an unpaired Student’s t-test was performed). C) Colloidal stability of the CP-based SERRS-nanoprobes as determined by LSPR measurements (n=3; error bars represent standard deviations; See also Supplementary Figure 2; Supplementary Table 1).

Mentions: We also examined the SERRS-signal intensity as a function of the number of sulfur atoms in the dye. Sulfur-containing functionality has been used frequently to adhere molecules to gold,33 with several reports using thiol or lipoic acid functional groups to add sulfur-containing functionality.21, 34 In our structures, 2-thienyl groups attached to the 2- and 6- positions of the dye were used to bind the dyes to the gold surface. We also explored the impact of the chalcogen atoms in the chalcogenopyrylium core, switching a Se (1a and 2a) to S (1b and 2b). The chalcogen switch was used to increase semi-covalent interactions with the gold surface, and also to create a chromophore that had a more resonant absorption with the 785-nm detection laser (Table 1). Chalcogenopyrylium dyes 1–3 were used at a final concentration of 1.0 μM, which prevented nanoparticle aggregation for dye 3. Figure 3A shows the molecular structures of the chalcogenopyrylium dyes. The SERRS intensity of the different as-synthesized pyrylium-based SERRS-nanoprobes, which were synthesized at equimolar reporter concentrations, were measured at equimolar SERRS-nanoprobe concentrations at low laser power to prevent CCD-saturation (50 μW, 1.0 s acquisition time, 5× objective). We specifically focused on the 1600 cm−1 peak, which corresponds to aromatic ring stretching modes; and is a mode shared by chalcogenopyrylium dyes 1–3. The SERRS-signal intensity of the 1600 cm−1 peak increased significantly as the number of 2-thienyl substituents increased (Figure 3B, Supplementary Table 1) without causing significant aggregation (Figure 3C, Supplementary Figure 2 and Supplementary Table 1). Thus, 3 produced the highest SERRS-signal, which was significantly more intense than 2a/2b or 1a/1b (P<0.05) and 2a/2b were significantly more intense than 1a/1b (P<0.05). There was a less noticeable, but significant, increase from the chalcogen switch in the core (1a/1b and 2a/2b being significantly different (P<0.05)). This strongly supports the hypothesis that 2-thienyl groups are an effective means of adhering dyes to gold, resulting in brighter SERRS-nanoprobes.


Rational design of a chalcogenopyrylium-based surface-enhanced resonance Raman scattering nanoprobe with attomolar sensitivity.

Harmsen S, Bedics MA, Wall MA, Huang R, Detty MR, Kircher MF - Nat Commun (2015)

The SERRS-intensity as a function of dye affinity for the gold surface(A) Molecular structures of the adsorbed CP-dyes (1–3) arranged by increased number of 2-thienyl substituents (Ph, phenyl). (B) SERRS spectra of the CP-based SERRS-nanoprobes. The SERRS spectra were baseline corrected to allow proper comparison. (For the non-baseline corrected spectra see Supplementary Figure 3). Inset: intensity of the 1600 cm−1 peak (n=3; error bars represent standard deviations, *P<0.05; an unpaired Student’s t-test was performed). C) Colloidal stability of the CP-based SERRS-nanoprobes as determined by LSPR measurements (n=3; error bars represent standard deviations; See also Supplementary Figure 2; Supplementary Table 1).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4372816&req=5

Figure 3: The SERRS-intensity as a function of dye affinity for the gold surface(A) Molecular structures of the adsorbed CP-dyes (1–3) arranged by increased number of 2-thienyl substituents (Ph, phenyl). (B) SERRS spectra of the CP-based SERRS-nanoprobes. The SERRS spectra were baseline corrected to allow proper comparison. (For the non-baseline corrected spectra see Supplementary Figure 3). Inset: intensity of the 1600 cm−1 peak (n=3; error bars represent standard deviations, *P<0.05; an unpaired Student’s t-test was performed). C) Colloidal stability of the CP-based SERRS-nanoprobes as determined by LSPR measurements (n=3; error bars represent standard deviations; See also Supplementary Figure 2; Supplementary Table 1).
Mentions: We also examined the SERRS-signal intensity as a function of the number of sulfur atoms in the dye. Sulfur-containing functionality has been used frequently to adhere molecules to gold,33 with several reports using thiol or lipoic acid functional groups to add sulfur-containing functionality.21, 34 In our structures, 2-thienyl groups attached to the 2- and 6- positions of the dye were used to bind the dyes to the gold surface. We also explored the impact of the chalcogen atoms in the chalcogenopyrylium core, switching a Se (1a and 2a) to S (1b and 2b). The chalcogen switch was used to increase semi-covalent interactions with the gold surface, and also to create a chromophore that had a more resonant absorption with the 785-nm detection laser (Table 1). Chalcogenopyrylium dyes 1–3 were used at a final concentration of 1.0 μM, which prevented nanoparticle aggregation for dye 3. Figure 3A shows the molecular structures of the chalcogenopyrylium dyes. The SERRS intensity of the different as-synthesized pyrylium-based SERRS-nanoprobes, which were synthesized at equimolar reporter concentrations, were measured at equimolar SERRS-nanoprobe concentrations at low laser power to prevent CCD-saturation (50 μW, 1.0 s acquisition time, 5× objective). We specifically focused on the 1600 cm−1 peak, which corresponds to aromatic ring stretching modes; and is a mode shared by chalcogenopyrylium dyes 1–3. The SERRS-signal intensity of the 1600 cm−1 peak increased significantly as the number of 2-thienyl substituents increased (Figure 3B, Supplementary Table 1) without causing significant aggregation (Figure 3C, Supplementary Figure 2 and Supplementary Table 1). Thus, 3 produced the highest SERRS-signal, which was significantly more intense than 2a/2b or 1a/1b (P<0.05) and 2a/2b were significantly more intense than 1a/1b (P<0.05). There was a less noticeable, but significant, increase from the chalcogen switch in the core (1a/1b and 2a/2b being significantly different (P<0.05)). This strongly supports the hypothesis that 2-thienyl groups are an effective means of adhering dyes to gold, resulting in brighter SERRS-nanoprobes.

Bottom Line: Raman imaging has surfaced as a promising optical modality that offers both.Here we report the design and synthesis of a group of near-infrared absorbing 2-thienyl-substituted chalcogenopyrylium dyes tailored to have high affinity for gold.When adsorbed onto gold nanoparticles, these dyes produce biocompatible SERRS nanoprobes with attomolar limits of detection amenable to ultrasensitive in vivo multiplexed tumour and disease marker detection.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, USA.

ABSTRACT
High sensitivity and specificity are two desirable features in biomedical imaging. Raman imaging has surfaced as a promising optical modality that offers both. Here we report the design and synthesis of a group of near-infrared absorbing 2-thienyl-substituted chalcogenopyrylium dyes tailored to have high affinity for gold. When adsorbed onto gold nanoparticles, these dyes produce biocompatible SERRS nanoprobes with attomolar limits of detection amenable to ultrasensitive in vivo multiplexed tumour and disease marker detection.

No MeSH data available.


Related in: MedlinePlus