Rapid liposome quality assessment using a lab-on-a-chip

Abstract

Although liposomes have many outstanding features such as biocompatibility, biodegradability, low toxicity and structural diversity, and are successfully applied in many areas of chemistry and biotechnology, a lack of characterization standards and quality control tools are still inhibiting the translation of liposome technology into clinical routine. The greatest obstacle to clinical scale commercialization is the inability to ensure liposome formulation stability because small size variations or altered surface chemistries can significantly influence in vivo distribution and excretion kinetics that could in turn lead to unpredictable therapy outcomes. To enhance the product development process we have developed a microfluidic biochip containing embedded dielectric microsensors capable of providing quantitative results on formulation composition and stability based on the monitoring of the unique electric properties of liposomes. Computational fluid dynamic (CFD) simulations confirmed that microfluidics offer reproducible and well-defined measurement conditions where a moving liposome suspension within a microchannel behaves like a bulk material. Results of this study demonstrate the ability of microfluidics, in combination with dielectric spectroscopy and multivariate data analysis methods, to identify nine different liposomes. We also show that various liposome modifications such as membrane-bound surface proteins, lipid bilayer soluble drugs, as well as protein and dye encapsulations, can be detected in the absence of any labels or indicators. Since shelf-life stability of a liposome formulation is regarded of prime importance for regulatory approval and clinical application, we further provide a possible practical application of the developed liposome analysis platform as a high-throughput tool for industrial quality insurance purposes.

Microfluidic technologies for accelerating the clinical translation of nanoparticles

“…At present, there are microfluidic systems capable of characterizing the nanoparticle size and stability following synthesis in a single platform 31,32 . Moreover, large numbers of distinct nanoparticles can be obtained through combinatorial synthesis 33 , and production rates of identical nanoparticles can be increased through parallelization or re-design of the devices 34,35 .…”

Liposomal nanotransporter for targeted binding based on nucleic acid anchor system

“…A). Multifunctional envelope‐type nanodevices are very promising nonviral gene delivery vectors because they are biocompatible and enable programmed packaging of various functional elements into an individual nanostructured liposome , with subsequent use for lab, on a chip technology .…”

Modeling of cell sorting and rare cell capture with microfabricated biodevices

“…Although most published studies treated cells in the fluid sample as a continuous material (also referred to as continuum) [29,30] and the whole sample as a one-phase mixture of miscible liquids, some authors considered rare cell-containing flowing fluids as two-phase flow [31]. In the case of devices where a simple topology of channels (e.g., straight channel or T junction) was used without any barriers, single-phase continuum-based approaches resulted in realistic flow characteristics.…”