A comparison of background membrane imaging versus flow technologies for subvisible particle analysis of biologics

Vargas, Stephanie K.; Eskafi, Aydin; Carter, Eric; Ciaccio, Natalie

doi:10.1016/j.ijpharm.2020.119072

Cited by 17 publications

(3 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Particulate analysis was performed using backgrounded membrane imaging, or BMI (Aura, Halo Laboratories). , Background images were acquired of empty filter plate wells, sample was added and filtered to retain micrometer-sized particulates, membranes were rinsed and filtered with DI to remove soluble well residues, and then images were reacquired with both brightfield and darkfield illuminations. Images were analyzed for particulate size and morphology using the device software Particle Vu 3.2.…”

Section: Methodsmentioning

confidence: 99%

DNA Released by Adeno-Associated Virus Strongly Alters Capsid Aggregation Kinetics in a Physiological Solution

Jarand,

Baker,

Petroff

et al. 2024

Biomacromolecules

View full text Add to dashboard Cite

While adeno-associated virus is a leading vector for gene therapy, significant gaps remain in understanding AAV degradation and stability. In this work, we study the degradation of an engineered AAV serotype at physiological pH and ionic strength. Viral particles of varying fractions of encapsulated DNA were incubated between 30 and 60 °C, with changes in molecular weight measured by changes in total light scattering intensity at 90°o ver time. Mostly full vectors demonstrated a rapid decrease in molecular weight corresponding to the release of capsid DNA, followed by slow aggregation. In contrast, empty vectors demonstrated immediate, rapid colloid-type aggregation. Mixtures of full and empty capsids showed a pronounced decrease in initial aggregation that cannot be explained by a linear superposition of empty and full degradation scattering signatures, indicating interactions between capsids and ejected DNA that influenced aggregation mechanisms. This demonstrates key interactions between AAV capsids and their cargo that influence capsid degradation, aggregation, and DNA release mechanisms in a physiological solution.

show abstract

Section: Methodsmentioning

confidence: 99%

DNA Released by Adeno-Associated Virus Strongly Alters Capsid Aggregation Kinetics in a Physiological Solution

Jarand,

Baker,

Petroff

et al. 2024

Biomacromolecules

View full text Add to dashboard Cite

show abstract

“…However, use of newer analytic techniques such as flow imaging (FI) and backgrounded membrane imaging (BMI) allow for improved identification of particle morphology and a more accurate characterization of particles in solution, which may provide greater insight into particulate being infused. 21 In the setting of protein aggregate research, FI and BMI have significant data to support their use to augment current USP <788> methods. However, to date, it does not appear that FI or BMI have been used to evaluate small molecules in the setting of IV medication compatibility.…”

Section: Introductionmentioning

confidence: 99%

“…Light obscuration (LO) and microscopic particle count tests are the two specific methods within the USP for quantifying subvisible particles. However, use of newer analytic techniques such as flow imaging (FI) and backgrounded membrane imaging (BMI) allow for improved identification of particle morphology and a more accurate characterization of particles in solution, which may provide greater insight into particulate being infused 21 . In the setting of protein aggregate research, FI and BMI have significant data to support their use to augment current USP <788> methods.…”

Section: Introductionmentioning

confidence: 99%

Physical compatibility of medications with concentrated neonatal and pediatric parenteral nutrition: A simulated Y‐site drug compatibility study

Ross

Petty

Salinas

et al. 2023

J Parenter Enteral Nutr

View full text Add to dashboard Cite

Background:The physical intravenous Y-site compatibility of 15 different medications with highly concentrated neonatal and pediatric parenteral nutrition (PN) compounds is described, using existing and novel methods.Methods: PN formulations were developed based on common prescribing practices in a 400+-bed freestanding children's hospital. Medications at commonly used pediatric concentrations were mixed in a 1:1 ratio with both pediatric and neonatal PN formulations and incubated at room temperature for 4 h to simulate Y-site administration. Samples were then analyzed using the light obscuration (LO) technique, as recommended by United States Pharmacopeia (USP) chapter <788>, in addition to novel flow imaging (FI) microscopy and backgrounded membrane imaging (BMI). Physical compatibility was determined using USP <788> particle count limits for all techniques.Results: Most combinations were found to be compatible per USP <788> thresholds.Pediatric PN was incompatible by at least two methods with cisatracurium 2 mg/ml, sildenafil 0.8 mg/ml, furosemide 10 mg/ml, and ketamine 10 mg/ml. Neonatal PN was incompatible by at least two methods with cisatracurium 2 mg/ml and furosemide 10 mg/ml. Overall, results for 20 of the 30 combinations (66%) agreed across all three methods. FI and BMI results agreed for 22 of 30 combinations. LO agreed with FI in 25 of 30 combinations, and BMI and LO results agreed in 23 of 30 combinations. Conclusion:Most combinations tested were found to be compatible across all methods. Novel methods of FI and BMI seem useful to further evaluate LO findings and improve accuracy of particle counts when assessing PN-medication combinations.

show abstract

FlowCam 8400 and FlowCam Cyano Phytoplankton Classification and Viability Staining by Imaging Flow Cytometry

Roache-Johnson

Stephens

2023

Methods in Molecular Biology

View full text Add to dashboard Cite

A comparison of background membrane imaging versus flow technologies for subvisible particle analysis of biologics

Cited by 17 publications

References 20 publications

DNA Released by Adeno-Associated Virus Strongly Alters Capsid Aggregation Kinetics in a Physiological Solution

DNA Released by Adeno-Associated Virus Strongly Alters Capsid Aggregation Kinetics in a Physiological Solution

Physical compatibility of medications with concentrated neonatal and pediatric parenteral nutrition: A simulated Y‐site drug compatibility study

FlowCam 8400 and FlowCam Cyano Phytoplankton Classification and Viability Staining by Imaging Flow Cytometry

Contact Info

Product

Resources

About