Microfluidically Assisted Synthesis of Calcium Carbonate Submicron Particles with Improved Loading Properties

Abstract

The development of advanced methods for the synthesis of nano- and microparticles in the field of biomedicine is of high interest due to a range of reasons. The current synthesis methods may have limitations in terms of efficiency, scalability, and uniformity of the particles. Here, we investigate the synthesis of submicron calcium carbonate using a microfluidic chip with a T-shaped oil supply for droplet-based synthesis to facilitate control over the formation of submicron calcium carbonate particles. The design of the chip allowed for the precise manipulation of reaction parameters, resulting in improved porosity while maintaining an efficient synthesis rate. The pore size distribution within calcium carbonate particles was estimated via small-angle X-ray scattering. This study showed that the high porosity and reduced size of the particles facilitated the higher loading of a model peptide: 16 vs. 9 mass.% for the particles synthesized in a microfluidic device and in bulk, correspondingly. The biosafety of the developed particles in the concentration range of 0.08–0.8 mg per plate was established by the results of the cytotoxicity study using mouse fibroblasts. This innovative approach of microfluidically assisted synthesis provides a promising avenue for future research in the field of particle synthesis and drug delivery systems.

Optimization of a tunable process for rapid production of calcium phosphate microparticles using a droplet-based microfluidic platform

“…In-droplet synthesis of other inorganic microparticles has also been reported. Ermakov et al, for example, have recently generated monodisperse calcium carbonate micro- and nanoparticles using a droplet-generating microfluidic device, and used the resulting particles as carriers of a model peptide ( Ermakov et al, 2024 ). It is known that producing CaP microparticles in the range of 100–300 µm using conventional particle production methods is challenging ( Bohner et al, 2013 ).…”

Synthesis of Submicron CaCO3 Particles in 3D-Printed Microfluidic Chips Supporting Advection and Diffusion Mixing

“…Despite significant advancements, only a small number of nanoparticles in medicine reach the stage of clinical trials and receive approval [7,8]. Micro-and nanoparticle platforms based on calcium carbonate (CaCO 3 ) promise advancing drug delivery in cancer therapy [9,10]. To minimize the off-targeting effect, controlled-release systems responsive to external conditions like temperature, enzyme activity, or pH emerge as a viable approach [9,11].…”

“…Additive manufacturing, or 3D printing, is increasingly used for making microfluidic devices. Techniques like stereolithography allow for the precise fabrication of intricate geometries for PDMS master molds [8,10]. Advantages include rapid prototyping, customization, and integration of multiple functions.…”

Recent Advances in Magnetically Actuated Droplet Manipulation for Biomedical Applications

“…Droplets refer to the fine liquid particles that can settle under static conditions and remain suspended even amid turbulent circumstances [1]. In contemporary times, the manipulation of droplets has become a focal point of interest in the fields of biomedicine [2][3][4][5], chemistry [6][7][8], and hydromechanics [9][10][11] due to the advantages of droplets' flexibility and independence [12]. Concomitant with the progress in microfluidic technologies, droplet microfluidics realizes the flow control of microdroplets and builds a new platform for biological and medical research.…”