SERS Tag Manufacturing via Controlled Aggregation

The patent applies preliminary action by controlling the aggregation process during synthesis to directly produce SERS tags with desired aggregate distribution, rather than sorting after synthesis. The controlled aggregation synthetic process pre-establishes the narrow size distribution and high ratio of low-number aggregates during the manufacturing process itself, eliminating the need for subsequent time-consuming sorting operations.

The patent extracts the sorting step from the overall manufacturing process by implementing controlled aggregation during synthesis. This removes the separate post-synthetic sorting operation (which required high viscosity density gradient media and centrifugation) and integrates the size control function directly into the aggregation process, thereby eliminating the time and resource overhead of extraction-based sorting.

The patent applies preliminary action by controlling the aggregation process during synthesis to directly produce SERS tags with desired aggregate distribution, rather than sorting after synthesis. The controlled aggregation synthetic process pre-establishes the narrow size distribution and high ratio of low-number aggregates during the manufacturing process itself, eliminating the need for subsequent expensive sorting operations.

The patent employs simple, inexpensive reagents for controlled aggregation (such as salts, pH adjusters, or small molecules) that can be easily removed or are biocompatible, replacing the expensive high viscosity density gradient media (iodixanol) required for post-synthetic sorting. This substitution with cheaper, more accessible materials significantly reduces production costs.

The patent extracts the solid support from the aggregation process, performing controlled aggregation in homogeneous solution instead. This eliminates the solid support surface that would otherwise compete with Raman active reporter molecules for nanoparticle surface binding sites, thereby maximizing the surface area available for reporter molecule adsorption while still achieving narrow size distribution through solution-based controlled aggregation.

The patent uses small molecule mediators (such as salts, pH adjusters, or weak-binding ligands) to control aggregation in solution, replacing the solid support intermediary. These mediators temporarily facilitate controlled aggregation during synthesis but do not permanently bind to the nanoparticle surface, leaving maximum surface area available for Raman active reporter molecule adsorption.

The patent extracts the solid support and associated lengthy processing steps from the aggregation process. By performing controlled aggregation in homogeneous solution with simple reagents, the method eliminates time-consuming steps such as solid support functionalization, multiple washing cycles, and complex separation procedures, thereby achieving narrow size distribution in significantly reduced production time.

The patent skips the lengthy solid support assisted aggregation protocol and implements a streamlined solution-based controlled aggregation process. This rushed-through approach uses simple pH adjustment or salt addition to rapidly control aggregation kinetics, achieving narrow size distribution in minutes rather than hours, thereby significantly improving production throughput.