Lipid Nanoparticle Solutions

Lipid Nanoparticle Solutions

Gain insights to intact particles and molecular compositions with purposefully designed lipid nanoparticle (LNP) solutions from Waters that generate high quality, reliable analytical data.

Gain insights to intact particles and molecular compositions with purposefully designed lipid nanoparticle (LNP) solutions from Waters that generate high quality, reliable analytical data.
Characterize LNPs to ensure product safety and efficacy.
Characterize LNPs to ensure product safety and efficacy.

Overview

Lipid nanoparticles (LNPs) are used to encapsulate and deliver nucleic acid, protein, and small molecule drugs into targeted cells. Celebrated as the delivery vehicles for the first mRNA vaccines, LNPs continue to be the focus of intense development efforts aimed at delivering new mRNA therapeutics and vaccines. 

Waters comprehensive and integrated solutions ensure critical quality attributes, including size and polydispersity index (PDI), encapsulation efficiency, particle morphology and stability, and lipid composition are accurately assessed. With robust LC and LC-MS technologies, dynamic light scattering (DLS), and microcalorimetry for the thermodynamics of an LNP sample, Waters solutions deliver powerful performance to increase the analytical sensitivity of your LNP workflow. 

Download the Characterizing LNP mRNA Guide eBook

Applications

The Andrew+ pipetting robot and DynaPro DLS Plate Reader simplify the laborious and expensive task of LNP formulation development. They automate screening and directly measure size and polydispersity, improving efficiency and precision. In production, the ultraDAWN real-time MALS provides continuous monitoring for product consistency.

The Andrew+ pipetting robot and DynaPro DLS Plate Reader simplify the laborious and expensive task of LNP formulation development. They automate screening and directly measure size and polydispersity, improving efficiency and precision. In production, the ultraDAWN real-time MALS provides continuous monitoring for product consistency.

Application Notes

The heat map display in DYNAMICS may be programmed to differentiate size distributions and visualize at a glance different degrees of aggregation. Data courtesy Sabin Vaccine Institute.

Chromatography with evaporative light scattering routinely separates and quantifies lipid components, ensuring purity and consistency in formulations. 
In addition to compositional profiling, impurity analysis is critical to understand the assembled delivery system and to screen lipid raw materials. 
Waters LNP LC-MS data workflow package facilitates compositional analysis of the lipids comprising the particle and identification of their impurities, enabling accurate formulation and quality control of LNP-based drugs.

Chromatography with evaporative light scattering routinely separates and quantifies lipid components, ensuring purity and consistency in formulations. 
In addition to compositional profiling, impurity analysis is critical to understand the assembled delivery system and to screen lipid raw materials. 
Waters LNP LC-MS data workflow package facilitates compositional analysis of the lipids comprising the particle and identification of their impurities, enabling accurate formulation and quality control of LNP-based drugs.

Application Notes

Overview of the integrated waters_connect workflow.

Field-flow fractionation coupled with multi-angle light scattering is a leading method for precise and quantitative analysis of LNPs. It allows simultaneous measurement of various quality attributes like size distribution, particle concentration, morphology, encapsulation efficiency, mRNA concentration, and lipid concentration.

Field-flow fractionation coupled with multi-angle light scattering is a leading method for precise and quantitative analysis of LNPs. It allows simultaneous measurement of various quality attributes like size distribution, particle concentration, morphology, encapsulation efficiency, mRNA concentration, and lipid concentration.

Application Notes

Comparison of mRNA-LNP samples with different mRNA content and empty particles. The LS fractograms at 90° MALS angle are shown overlaid with the ratio of rms radius and hydrodynamic radius, . The radio tracks the degree of encapsulated RNA.

Ensuring ideal particle size, uniformity, and surface charge is crucial for cellular uptake and safety. Light scattering combined with calorimetry measurements offers a comprehensive understanding of the stability of LNPs and liposomes, essential for formulation development, pH screening, and freeze-thaw studies.

Ensuring ideal particle size, uniformity, and surface charge is crucial for cellular uptake and safety. Light scattering combined with calorimetry measurements offers a comprehensive understanding of the stability of LNPs and liposomes, essential for formulation development, pH screening, and freeze-thaw studies.

Application Notes

Size, size distribution, and concentration of empty LNP prepared via microfluidic-mixing (S1), LNP with mRNA prepared via microfluidic-mixing (S2), LNP with mRNA prepared via hand-mixing (S3).

Webinar: LNP Composition & Impurities Analysis with Compliance-Ready LC & LC-MS Workflows

This webinar reviews LC-ELSD and LC-ELSD-MS workflows run under Empower CDS for deployment in regulated and non-regulated labs, and illustrates the importance of LNP composition and impurities analysis data. Guidance is provided on ELSD parameters that can be adjusted for optimum results. Access the webinar to learn more about LC-based lipid analyses.

This webinar reviews LC-ELSD and LC-ELSD-MS workflows run under Empower CDS for deployment in regulated and non-regulated labs, and illustrates the importance of LNP composition and impurities analysis data. Guidance is provided on ELSD parameters that can be adjusted for optimum results. Access the webinar to learn more about LC-based lipid analyses.
VIEW WEBINAR
Gene therapeutics can be one of many different modalities – from duplex GalNAc siRNA to LNP mRNA to an AAV vectored transgene.

Solutions

Waters LC and LC-MS systems offer leading separations performance and sensitivity for lipid nanoparticle (LNP) analysis.

Waters LC and LC-MS systems offer leading separations performance and sensitivity for lipid nanoparticle (LNP) analysis.

Efficient product attribute monitoring throughout development

Efficient product attribute monitoring throughout development
BioAccord LC-MS System with ACQUITY Premier

Simplify LNP analysis with Waters BioAccord LC-MS System with ACQUITY Premier, a fully integrated, compliance-ready platform deployable from discovery to GxP labs​.

  • Lipid Raw Material and LNP Composition Testing

The next evolution in separation science is here

The next evolution in separation science is here
ACQUITY Premier System

The ACQUITY Premier System features MaxPeak High Performance Surfaces (HPS) Technology, which offers improvements in separation and detection of metal-sensitive analytes, enabling you to minimize the risk of undetected analytes. 

  • Formulation Screening and Production
  • Lipid Raw Material and LNP Composition Testing
  • Size, Polydispersity and Payload Analysis
  • Surface Charge and Colloidal Stability Measurements

Separate beyond question with the power of mass detection

Separate beyond question with the power of mass detection
ACQUITY QDa II Mass Detector

Take single quadrupole performance to the next level with the ACQUITY QDa II Mass Detector that is easy to use, remarkably robust, and complementary to optical detection to confirm and monitor lipid impurities.

  • Lipid Raw Material and LNP Composition Testing

One system. Every analyte. All the time.

One system. Every analyte. All the time.
DAWN MALS

Obtain simultaneous measurement of particle size distribution, encapsulated payload concentration, particle concentration, morphology, and aggregation seamlessly and efficiently with Wyatt Technology’s DAWN-MALS, coupled with the ECLIPSE FFF or Waters Arc HPLC System.

  • Lipid Raw Material and LNP Composition Testing
  • Size, Polydispersity and Payload Analysis

Measure size and zeta potential in native buffer

Measure size and zeta potential in native buffer
DynaPro ZetaStar

Conduct DLS, SLS, and ELS all on one platform with the DynaPro ZetaStar instrument that integrates with Waters Arc HPLC System for automated Zeta potential measurement. 

  • Formulation Screening and Production
  • Size, Polydispersity and Payload Analysis

High-throughput size and stability screening

High-throughput size and stability screening
DynaPro DLS Plate Reader

Measure size, polydispersity and Tagg data for hundreds of samples with as little as 4ul per well in standard microplates with the DynaPro DLS Plate Reader, and process with any liquid handler to boost productivity.

  • Formulation Screening and Production
  • Surface Charge and Colloidal Stability Measurements

Real-time monitoring for product and process quality

Real-time monitoring for product and process quality
ultraDAWN real-time MALS

Measure and report molecular weight, size, and particle concentration in real time with ultraDAWN real-time MALS (RT-MALS) for rapid feedback on product and process quality.

  • Formulation Screening and Production

Heat capacity measurements to guide LNP formulation

Heat capacity measurements to guide LNP formulation
TA Instruments Nano DSC

Gain insight on the overall structure and stability of LNPs with the Nano DSC by monitoring temperature induced changes (melting temperature) of dilute in-solution biomolecules. 

  • Formulation Screening and Production

Waters software streamlines data acquisition, processing, and reporting lipid nanoparticle analysis results.

Waters software streamlines data acquisition, processing, and reporting lipid nanoparticle analysis results.

Dedicated waters_connect LNP data workflow package

Dedicated waters_connect LNP data workflow package
waters_connect for biopharmaceuticals

Accelerate your journey to informed decision-making with streamlined acquisition and processing methods​, LNP component and impurity characterization workflow​s, compound library​, report templates​, sample data sets​, and user guide.

  • Lipid Raw Material and LNP Composition Testing

Seamless MALS detector and HPLC/UHPLC integration

Seamless MALS detector and HPLC/UHPLC integration
HPLC Connect and ASTRA

Directly control your LC pumps and detectors in a single software ecosystem and unified interface with HPLC CONNECT for Waters that uses Wyatt Technology’s ASTRA software’s digital synchronization to minimize human error and ensure high confidence in data accuracy.

  • Formulation Screening and Production
  • Lipid Raw Material and LNP Composition Testing
  • Size, Polydispersity and Payload Analysis

Match MS spectral peaks with Empower CDS libraries

Match MS spectral peaks with Empower CDS libraries
Empower Chromatography Data System (CDS)

Users can build MS spectral libraries in Empower CDS for matching spectral peaks from samples that were collected in different projects and under different conditions. Filtering options increase the spectral matching accuracy.

  • Formulation Screening and Production
  • Lipid Raw Material and LNP Composition Testing
  • Size, Polydispersity and Payload Analysis

Columns and consumables for lipid separations that enable sensitive chromatography and mass spec workflows.

Columns and consumables for lipid separations that enable sensitive chromatography and mass spec workflows.

RPLC columns with unmatched peak shape and reliability

RPLC columns with unmatched peak shape and reliability
MaxPeak Premier CSH Phenyl Hexyl Columns for Lipid Analysis

Obtain unique selectivity for ionizable cationic lipids, critical to LNP formulations, with MaxPeak Premier CSH Phenyl Hexyl Columns for Lipid Analysis that incorporate Charge Surface Hybrid (CSH) Phenyl Hexyl particles to improve resolution and peak shape.

  • Formulation Screening and Production
  • Lipid Raw Material and LNP Composition Testing

Inert, high efficiency widepore SEC columns

Inert, high efficiency widepore SEC columns
GTxResolve SEC Columns

Expand your analytical possibilities with wide-pore GTxResolve SEC columns with MaxPeak Premier High Performance Surfaces hardware and a novel particle technologies that simplify LNP heterogeneity measurements and ensure efficient, high recovery separations.

  • Formulation Screening and Production
  • Size, Polydispersity and Payload Analysis

Orthogonal selectivities and ion pairing free column chromatography

Orthogonal selectivities and ion pairing free column chromatography
Gene-Based (GTx) Therapeutics Columns

Obtain orthogonal selectivity and ion pairing free LC options with Gene-Based (GTx) Therapeutics Columns, specifically designed for weak and strong anion exchange (AEX) and hydrophilic interaction chromatography (HILIC).

  • Formulation Screening and Production
  • Lipid Raw Material and LNP Composition Testing
  • Size, Polydispersity and Payload Analysis

Your success is just a click away

Your success is just a click away
Waters Global Services

Optimize your laboratory's productivity and success with Waters Global Services. Maintain peak system performance, minimize down time, address application challenges, and support stringent compliance requirements.

  • Formulation Screening and Production
  • Lipid Raw Material and LNP Composition Testing
  • Size, Polydispersity and Payload Analysis

Make science more accessible with Waters Capital

Make science more accessible with Waters Capital
Payment Solutions

Maximize resources and minimize risk with payment options from Waters Capital, including upgrading aging equipment, getting customized support, and bundling services into one monthly payment.

  • Formulation Screening and Production
  • Lipid Raw Material and LNP Composition Testing
  • Size, Polydispersity and Payload Analysis
  • Surface Charge and Colloidal Stability Measurements

The data speaks for itself

The data speaks for itself
Comparison of transfection efficiency into HepG2 cells of LNPs prepared using different methods.
Localization of oxidation on the Dlin-MC3-DMA molecule. Two structures are shown with possible locations for the oxidation, including (left) oxidation of the amine group of the polar head group and (right) epoxidation of one of the double bonds in the fatty acid chain. Below each structure are the low energy (parent ion) and high energy (fragment ion) spectra with matching fragment ions labeled based on in-silico prediction using each structure. Key fragment ions indicative of the location of the oxidation are labeled as A, B, and C. The fragment ion labeled D is the same peak as C but corresponds to an unlikely fragmentation in the epoxidated structure.
Aggregate content in a freshly prepared sample (red) and one which was stored for three months (blue). Top: the light scattering fractograms at 90° scattering angle. Peak 1 is centered around 17 minutes, Peak 2 around 31 minutes. The relative size of the aggregate peak (Peak 2) is significantly larger for the stored sample. Bottom: total particle concentrations, where Peak 2 contains 10 times more particles for the stored sample than for the fresh sample.
(A) Overlay of the effect of heating on Tm. 1st heat scan, red dash and 2nd heat scan, blue line (B) Effect of additives on liposome properties. Black = no cholesterol added, blue = moderate cholesterol percentage incorporated, red = high cholesterol percentage incorporated.

Webinars and Resources

  • eBook

Characterizing LNP mRNA Consumables

Characterizing LNP mRNA Consumables
Download
  • On Demand Webinar

Unveiling CQA Insights for mRNA, LNPs and Viral Vectors by SEC and MALS with GTxResolve Columns

Unveiling CQA Insights for mRNA, LNPs and Viral Vectors by SEC and MALS with GTxResolve Columns
Download

Related

Nucleic Acid Solutions
Waters offers a complete portfolio of liquid chromatography systems, instruments, mass spectrometers, and analytical solutions for nucleic acid research of long-chain varieties (mRNA, ssDNA, dsDNA).

Learn more about Lipid Nanoparticle Solutions.

Learn more about Lipid Nanoparticle Solutions.
Characterize LNPs to ensure product safety and efficacy.
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