Revisiting El-Sayed Synthesis: Bayesian Optimization for Revealing New Insights during the Growth of Gold Nanorods

In diverse fields, machine learning (ML) has sparked transformative changes, primarily driven by the wealth of big data. However, an alternative approach seeks to mine insights from “precious data”, offering the possibility to reveal missed knowledge and escape potential knowledge traps. In this context, Bayesian optimization (BO) protocols have emerged as crucial tools for optimizing the synthesis and discovery of a broad spectrum of compounds including nanoparticles. In our work, we aimed to go beyond the commonly explored experimental conditions and showcase a workflow capable of unearthing fresh insights, even in well-studied research domains. The growth of AuNRs is a nonequilibrium process that remains poorly understood despite the presence of well-established seeded growth protocols. Traditional research aimed at understanding the mechanism of AuNR growth has primarily relied on altering one reaction condition at a time. While these studies are undeniably valuable, they often fail to capture the synergies between different reaction conditions, thus constraining the depth of insights they can offer. In the present study, we exploit BO, to identify diverse experimental conditions yielding AuNRs with similar spectroscopic characteristics. Notably, we identify viable and accelerated synthesis conditions involving elevated temperatures (36–40 °C) as well as high ascorbic acid concentrations. More importantly, we note that ascorbic acid and temperature can modulate each other’s undesirable influences on the growth of AuNRs. Finally, by harnessing the power of interpretable ML algorithms, complemented by our deep chemical understanding, we revisited the established hierarchical relationships among reaction conditions that impact the El-Sayed-based growth of AuNRs

Tuning Gold Nanorod Synthesis through Prereduction with Salicylic Acid

Successful synthesis of gold nanorods requires subtle combination of additives and reducing species. The latter are of major importance, as the reducing power determines the rate of metallic gold formation, which often defines the final shape and anisotropy. Ascorbic acid is a common reducing agent in the synthesis of gold nanorods, but its relatively strong reducing power limits the tunability of the final shape and optical response. We propose here a bimodal reducing agent system comprising a combination of salicylic acid and ascorbic acid. While salicylic acid prereduces Au­(III) to Au­(I) in the growth solution, ascorbic acid participates in the autocatalytic reduction of Au­(I) to Au(0), selectively occurring on the metallic surface. This combination provides a fine control over gold reduction at any stage of nanorod formation, which in turn leads to improved monodispersity, better reduction yield, and morphology control

Nanoparticle-Based Discrimination of Single-Nucleotide Polymorphism in Long DNA Sequences

Circulating DNA (ctDNA) and specifically the detection cancer-associated mutations in liquid biopsies promises to revolutionize cancer detection. The main difficulty however is that the length of typical ctDNA fragments (∼150 bases) can form secondary structures potentially obscuring the mutated fragment from detection. We show that an assay based on gold nanoparticles (65 nm) stabilized with DNA (Au@DNA) can discriminate single nucleotide polymorphism in clinically relevant ssDNA sequences (70–140 bases). The preincubation step was crucial to this process, allowing sequential bridging of Au@DNA, so that single base mutation can be discriminated, down to 100 pM concentration

Robust Rules for Optimal Colorimetric Sensing Based on Gold Nanoparticle Aggregation

Spurred by outstanding optical properties, chemical stability, and facile bioconjugation, plasmonic metals have become the first-choice materials for optical signal transducers in biosensing. While the design rules for surface-based plasmonic sensors are well-established and commercialized, there is limited knowledge of the design of sensors based on nanoparticle aggregation. The reason is the lack of control over the interparticle distances, number of nanoparticles per cluster, or multiple mutual orientations during aggregation events, blurring the threshold between positive and negative readout. Here we identify the geometrical parameters (size, shape, and interparticle distance) that allow for maximizing the color difference upon nanoparticle clustering. Finding the optimal structural parameters will provide a fast and reliable means of readout, including unaided eye inspection or computer vision

Sensitivity Limit of Nanoparticle Biosensors in the Discrimination of Single Nucleotide Polymorphism

Detection of single nucleotide polymorphism (SNP) by selective aggregation of nanoparticles offers a rapid determination of cancer biomarkers, detectable by the naked eye. The main factor limiting the sensitivity of such colloidal sensors is the number of available target DNA molecules that can induce aggregation and thereby transduce an optical output signal. Although particle size is an obvious parameter of choice toward the modulation of the target-to-particle ratio at constant metal concentration, it is often omitted due to difficulties in the synthesis of particles with suitable size or to the limited colloidal stability of large particles stabilized with DNA. We present here a systematic study of SNP detection using gold nanoparticles of various sizes (13, 46, and 63 nm), using a conventional sandwich assay. We found that a 5-fold increase in particle size, at constant gold concentration, leads to an improvement in the limit of detection by 3 orders of magnitude, which is 5, 0.1, and 0.05 nM for 13, 46, and 63 nm, respectively. This assay allows the SNP detection down to 10.85 fmol within less than 10 min. We conclude that a target-to-particle ratio equal to 4 sets the limit of detection and sensitivity of the assay, regardless of particle size

Electro- and Photochemical Water Oxidation on Ligand-free Co₃O₄ Nanoparticles with Tunable Sizes

Splitting of water to hydrogen and oxygen on colloidal catalysts is a promising method for future energy and chemistry cycles. The currently used high-performance oxides containing expensive elements (Ru, Ir) are progressively being replaced by more sustainable ones, such as Co₃O₄. Although the size of the nanoparticles determines their catalytic performance, the control over the particles’ diameter is often synthetically difficult to achieve. An additional obstacle is the presence of stabilizing agent, an organic molecule that blocks accessible surface-active centers. Herein, we present how precise control over size of the cobalt oxide nanoparticles (Co₃O₄ NPs), their colloidal stability, and the ligand-free surface affect overall performance of the photocatalytic oxygen evolution. We accordingly correlated the photochemical results with the electrochemical studies, concluding that accessibility of the active species on the particles’ surface is crucial parameter in water oxidation

Residual CTAB Ligands as Mass Spectrometry Labels to Monitor Cellular Uptake of Au Nanorods

Gold nanorods have numerous applications in biomedical research, including diagnostics, bioimaging, and photothermal therapy. Even though surfactant removal and surface conjugation with antifouling molecules such as polyethylene glycol (PEG) are required to minimize nonspecific protein binding and cell uptake, the reliable characterization of these processes remains challenging. We propose here the use of laser desorption/ionization mass spectrometry (LDI-MS) to study the ligand exchange efficiency of cetyltrimethylammonium bromide (CTAB)-coated nanorods with different PEG grafting densities and to characterize nanorod internalization in cells. Application of LDI-MS analysis shows that residual CTAB consistently remains adsorbed on PEG-capped Au nanorods. Interestingly, such residual CTAB can be exploited as a mass barcode to discern the presence of nanorods in complex fluids and in vitro cellular systems, even at very low concentrations

High-Yield Seeded Growth of Monodisperse Pentatwinned Gold Nanoparticles through Thermally Induced Seed Twinning

We show that thermal treatment of small Au seeds results in extensive twinning and a subsequent drastic improvement in the yield (>85%) of formation of penta­twinned nanoparticles (NPs), with preselected morphology (nanorods, bipyramids, and decahedra) and aspect ratio. The “quality” of the seeds thus defines the yield of the obtained NPs, which in the case of nanorods avoids the need for additives such as Ag⁺ ions. This modified seeded growth method also improves reproducibility, as the seeds can be stored for extended periods of time without compromising the quality of the final NPs. Additionally, minor modification of the seeds with Pd allows their localization within the final particles, which opens new avenues toward mechanistic studies. Together, these results represent a paradigm shift in anisotropic gold NP synthesis

Conjugated Polymers As Molecular Gates for Light-Controlled Release of Gold Nanoparticles

The remote release of nano-objects from a container is a promising approach to transduce chemical events into an optical signal. The major challenge in the development of such a system involves the use of a suitable molecular gate that retains aggregated particles and releases them upon applying an external stimulus. We show proof-of-concept experiments for the release of gold nanoparticles into an aqueous solution upon photodegradation of conjugated polymer thin films. Gold nanoparticles thus transduce light-induced chemical events into an amplified optical signal with a release rate of 2.5 nM per hour, which can be readily detected by the naked eye

Silver Ions Direct Twin-Plane Formation during the Overgrowth of Single-Crystal Gold Nanoparticles

It is commonly agreed that the crystalline structure of seeds dictates the crystallinity of final nanoparticles in a seeded-growth process. Although the formation of monocrystalline particles does require the use of single-crystal seeds, twin planes may stem from either single- or polycrystalline seeds. However, experimental control over twin-plane formation remains difficult to achieve synthetically. Here, we show that a careful interplay between kinetics and selective surface passivation offers a unique handle over the emergence of twin planes (in decahedra and triangles) during the growth over single-crystalline gold nanoparticles of quasi-spherical shape. Twinning can be suppressed under conditions of slow kinetics in the presence of silver ions, yielding single-crystalline particles with high-index facets