PMID- 35049653 OWN - NLM STAT- MEDLINE DCOM- 20220315 LR - 20240130 IS - 2079-6374 (Electronic) IS - 2079-6374 (Linking) VI - 12 IP - 1 DP - 2022 Jan 5 TI - Substituent Effects Impact Surface Charge and Aggregation of Thiophenol-Labeled Gold Nanoparticles for SERS Biosensors. LID - 10.3390/bios12010025 [doi] LID - 25 AB - SERS immunoassay biosensors hold immense potential for clinical diagnostics due to their high sensitivity and growing interest in multi-marker panels. However, their development has been hindered by difficulties in designing compatible extrinsic Raman labels. Prior studies have largely focused on spectroscopic characteristics in selecting Raman reporter molecules (RRMs) for multiplexing since the presence of well-differentiated spectra is essential for simultaneous detection. However, these candidates often induce aggregation of the gold nanoparticles used as SERS nanotags despite their similarity to other effective RRMs. Thus, an improved understanding of factors affecting the aggregation of RRM-coated gold nanoparticles is needed. Substituent electronic effects on particle stability were investigated using various para-substituted thiophenols. The inductive and resonant effects of functional group modifications were strongly correlated with nanoparticle surface charge and hence their stability. Treatment with thiophenols diminished the negative surface charge of citrate-stabilized gold nanoparticles, but electron-withdrawing substituents limited the magnitude of this diminishment. It is proposed that this phenomenon arises by affecting the interplay of competing sulfur binding modes. This has wide-reaching implications for the design of biosensors using thiol-modified gold surfaces. A proof-of-concept multiplexed SERS biosensor was designed according to these findings using the two thiophenol compounds with the most electron-withdrawing substitutions: NO(2) and CN. FAU - File, Nolan AU - File N AUID- ORCID: 0000-0001-9940-2410 AD - Sanguine Diagnostics and Therapeutics Inc., Omaha, NE 68106, USA. AD - School of Chemistry, University of Edinburgh, Edinburgh EH8 9YL, UK. FAU - Carmicheal, Joseph AU - Carmicheal J AUID- ORCID: 0000-0002-9669-8241 AD - Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA. FAU - Krasnoslobodtsev, Alexey V AU - Krasnoslobodtsev AV AUID- ORCID: 0000-0001-9233-0936 AD - Department of Physics, University of Nebraska at Omaha, Omaha, NE 68182, USA. FAU - Japp, Nicole C AU - Japp NC AUID- ORCID: 0000-0002-6672-5640 AD - Sanguine Diagnostics and Therapeutics Inc., Omaha, NE 68106, USA. FAU - Souchek, Joshua J AU - Souchek JJ AUID- ORCID: 0000-0002-7607-2823 AD - Sanguine Diagnostics and Therapeutics Inc., Omaha, NE 68106, USA. FAU - Chakravarty, Sudesna AU - Chakravarty S AD - Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA. FAU - Hollingsworth, Michael A AU - Hollingsworth MA AD - Sanguine Diagnostics and Therapeutics Inc., Omaha, NE 68106, USA. AD - Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA. AD - Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198, USA. AD - Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, USA. AD - Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198, USA. FAU - Sasson, Aaron A AU - Sasson AA AD - Sanguine Diagnostics and Therapeutics Inc., Omaha, NE 68106, USA. AD - Department of Surgery, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY 11794, USA. FAU - Natarajan, Gopalakrishnan AU - Natarajan G AD - Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA. FAU - Kshirsagar, Prakash G AU - Kshirsagar PG AD - Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA. FAU - Jain, Maneesh AU - Jain M AD - Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA. AD - Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, USA. FAU - Hayashi, Chihiro AU - Hayashi C AD - Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA. FAU - Junker, Wade M AU - Junker WM AD - Sanguine Diagnostics and Therapeutics Inc., Omaha, NE 68106, USA. AD - Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA. FAU - Kaur, Sukhwinder AU - Kaur S AD - Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA. FAU - Batra, Surinder K AU - Batra SK AUID- ORCID: 0000-0001-9470-9317 AD - Sanguine Diagnostics and Therapeutics Inc., Omaha, NE 68106, USA. AD - Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA. AD - Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198, USA. AD - Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, USA. LA - eng GR - R41CA213718/CA/NCI NIH HHS/United States GR - U01CA200466/CA/NCI NIH HHS/United States GR - U01CA210240/CA/NCI NIH HHS/United States GR - R41 CA213718/CA/NCI NIH HHS/United States GR - U01 CA210240/CA/NCI NIH HHS/United States PT - Journal Article DEP - 20220105 PL - Switzerland TA - Biosensors (Basel) JT - Biosensors JID - 101609191 RN - 0 (Phenols) RN - 0 (Sulfhydryl Compounds) RN - 7440-57-5 (Gold) RN - 7K011JR4T0 (thiophenol) SB - IM MH - *Biosensing Techniques MH - Gold MH - *Metal Nanoparticles MH - Phenols MH - Spectrum Analysis, Raman MH - Sulfhydryl Compounds PMC - PMC8773556 OTO - NOTNLM OT - Raman reporter molecules OT - SERS OT - aggregation OT - immunoassay OT - multiplexing OT - nanoparticles COIS- A.R.S., M.A.H. and S.K.B. have an equity interest in Sanguine Diagnostics and Therapeutics. N.F., N.C.J., J.J.S. and W.M.J. are/were employed by Sanguine Diagnostics and Therapeutics. All other authors declare no competing interest. EDAT- 2022/01/21 06:00 MHDA- 2022/03/16 06:00 PMCR- 2022/01/05 CRDT- 2022/01/20 12:26 PHST- 2021/11/24 00:00 [received] PHST- 2021/12/21 00:00 [revised] PHST- 2021/12/30 00:00 [accepted] PHST- 2022/01/20 12:26 [entrez] PHST- 2022/01/21 06:00 [pubmed] PHST- 2022/03/16 06:00 [medline] PHST- 2022/01/05 00:00 [pmc-release] AID - bios12010025 [pii] AID - biosensors-12-00025 [pii] AID - 10.3390/bios12010025 [doi] PST - epublish SO - Biosensors (Basel). 2022 Jan 5;12(1):25. doi: 10.3390/bios12010025.