Nanoparticles are specialized structures typically ranging in size from 1 to 100 nm. The term may also refer to larger particles (up to 500 nm), or fibers and tubes <100 nm in at least two dimensions. Owing to their nanoscale size and high surface area-to-volume ratio, nanoparticles are widely used in diagnostics, drug delivery systems, and therapeutics. Some common examples of nanoparticles include lipid nanoparticles (LNPs), liposomes, endogenous nanoparticles (exosomes), metal nanoparticles (MNPs), and polymeric nanoparticles.
A typical production workflow for nanoparticles involves four key steps: synthesis, harvesting, purification, and final formulation. The nanoparticles are synthesized using physical, chemical, and biological methods, each providing unique advantages for controlling particle size, shape, and composition tailored to specific applications.
After synthesis, nanoparticles are harvested using methods such as centrifugation, evaporation, ultrafiltration, or precipitation followed by purification. Keeping in view the stability, structural integrity, and effectiveness for downstream applications, nanoparticles are formulated using techniques such as dialysis, chromatography, or ultrafiltration. Therefore, factors like time efficiency, scalability, yield, and gentleness are crucial when choosing methods for harvesting and final formulation.
Production workflow of nanoparticles
Tables 1 and 2 present various techniques for harvesting and final formulation of nanoparticles, with ultrafiltration emerging as the most suitable method. However, despite being a common method, ultrafiltration using dead-end devices (called dead-end filtration or DEF) is limited by low filtration rates, scalability challenges, frequent sample loss, and manual interventions.
In contrast, ultrafiltration in the form of tangential flow filtration (TFF) offers higher filtration rates and scalability. However, traditional TFF systems are typically large and have high hold-up volumes, making them unsuitable for lab scale applications. To overcome these limitations, Formulatrix has developed the µPulse® - an automated and miniaturized TFF system designed specifically for sample concentration and buffer exchange at the lab scale.
| Considerations | Precipitation | Centrifugation | Evaporation |
Ultrafiltration Dead-End TFF |
|---|---|---|---|---|
| Gentleness | Moderate | Moderate | Low | Moderate High |
| Scalability | Moderate | Moderate | Moderate | Moderate High |
| Time Efficiency | Low | Low | Low | Low High |
| Cost Efficiency | Low | High | Moderate | Moderate High |
Table 1. Methods for nanoparticle harvesting
| Considerations | Dialysis | Chromatography |
Ultrafiltration Dead-End TFF |
|---|---|---|---|
| Gentleness | High | High | Moderate High |
| Scalability | Moderate | Moderate | Moderate High |
| Time Efficiency | Low | Low | Low High |
| Cost Efficiency | Moderate | Moderate | Moderate High |
Table 2. Methods for nanoparticle formulation
Nanoparticle Processing Using the µPulse - TFF System
The µPulse is an automated and miniaturized TFF system, explicitly designed for lab scale applications. It is well suited for the purification of a variety of nanoparticles including LNPs, liposomes, exosomes, MNPs, and polymeric nanoparticles.
The entire fluid path is miniaturized on the filter chip by combining microfluidic pumping technology with TFF. This has reduced the hold-up volume to just 0.65 mL, ensuring maximum hold-up recovery. The filter chips are available with modified polyethersulfone (mPES) and regenerated cellulose (RC) membranes that exhibit low fouling characteristics and are compatible with a variety of sample types.
The µPulse offers customizable parameters such as operating pressures and pump settings to optimize the processing of a variety of nanoparticles. Furthermore, it processes samples 4x faster compared to the dead-end centrifugal units, and in a walk-away approach.
Webinars
Discover how the silver nanoparticles are processed in a fast, single-step, and walk-away approach with the µPulse.
Learn a rapid, gentle, and automated approach for exosome harvesting and final formulation using the µPulse.