Evaluating nanomedicine with microfluidics

Abstract

Nanomedicines are engineered nanoscale structures that have an extensive range of application in the diagnosis and therapy of many diseases. Despite the rapid progress in and tremendous potential of nanomedicines, their clinical translational process is still slow, owing to the difficulty in understanding, evaluating, and predicting their behavior in complex living organisms. Microfluidic techniques offer a promising way to resolve these challenges. Carefully designed microfluidic chips enable in vivo microenvironment simulation and high-throughput analysis, thus providing robust platforms for nanomedicine evaluation. Here, we summarize the recent developments and achievements in microfluidic methods for nanomedicine evaluation, categorized into four sections based on their target systems: single cell, multicellular system, organ, and organism levels. Finally, we provide our perspectives on the challenges and future directions of microfluidics-based nanomedicine evaluation.

Advances in Computational Fluid Mechanics in Cellular Flow Manipulation: A Review

“…Microfluidics chips offer new approaches for cell assays and have also been used for studying of cell biology by providing platforms for manipulating, separating, sorting, filtering, trapping, and detecting tiny biological particles based on cellular heterogeneity. They can simulate small-scale fluid flow and chemical gradients and offer full manual control over the particles to study the desired details, e.g., for food market, clinical, pharmaceutical, and other applications [1][2][3][4][5][6][7]. Precise manipulations such as focusing, separation, and fractionation of cells is a vital capability of microfluidics which can be achieved by engineering hydrodynamics forces based on unique physical attributes of cells such as size [8,9], density [9,10], deformability [11][12][13], and morphology [14] using variety of methods such as crossflow filtration [15], electrode arrays [16], optical force switching [17] and other methods, some of and other methods, some of which can be found in detail in the review presented in [18].…”

“…Also, targeted drug delivery via nanomaterials, such as carbon nanotubes, was introduced recently and significantly increased the efficacy of the drugs [31][32][33][34]. As evaluation of these particles are highly dependent on their microenvironments, finding the optimum design point is facing some difficulties [35] and microfluidic systems can offer exceptional abilities to screen the nanoparticles to resolve these difficulties [1]. Zhu et al [36] presented an in-dept review of nanoparticle delivery steps in cellular flows and summarized several microfluidic models specialized in nanoparticle evaluations related to such investigations.…”

Ex vivo isolated human vessel perfusion system for the design and assessment of nanomedicines targeted to the endothelium

“…The predominant path for preclinical development of EC‐targeted NPs typically begins with static cell culture models . These in vitro models are easy to use, available to most laboratories, and produce clear quantitative readouts to assess targeting efficacy (i.e., mean fluorescence intensity of cells treated with NPs encapsulating fluorescent dye).…”

Evaluating Nanoparticles in Preclinical Research Using Microfluidic Systems

“…The 3D cell culture models such as tumor spheroids could mimic complex tissue structures to a certain extent, but failed to mimic the existence of chemical gradients and flow conditions. As a result, both 2D and 3D cell culture platforms could reach unmatched testing results compared with in vivo [21]. Animal models so far could best evaluate NPs in physiological conditions, however, their inherent inter-species variations in drug and NP responses as well as high cost and long testing periods require more human-relevant models.…”

“…Microfluidic systems can simulate dynamic fluid flows, chemical gradients, partitioning of multi-organs as well as local microenvironment controls, offering an efficient and cost-effective opportunity to fast screen NPs in terms of transport and efficacy for multiple clinical applications [21]. Currently most microfluidic reviews for NP performance testing are focusing on microfluidic techniques and characteristics [20,21,25,26,27], yet to categorize these systems based on their utilities in NP evaluation. Here, we are focusing on summarizing recent microfluidic systems demonstrated to be effective in different aspects of NP evaluations.…”