Hypothesis

Protein nanoparticles have attracted increased interest due to their broad applications ranging from drug delivery and vaccines to biocatalysts and biosensors. The morphology and the size of the nanoparticles play a crucial role in determining their suitability for different applications. Yet, effectively controlling the size of the nanoparticles is still a significant challenge in their manufacture. The hypothesis of this paper is that the assembly conditions and size of protein particles can be tuned via a mechanical route by simply modifying the mixing time and strength, while keeping the chemical parameters constant.

Experimental

We use an acoustically actuated, high throughput, ultrafast, microfluidic mixer for the assembly of protein particles with tuneable sizes. The performance of the acoustic micro-mixer is characterized via Laser Doppler Vibrometry and image processing. The assembly of protein nanoparticles is monitored by dynamic light scattering (DLS) and transmission electron microscopy (TEM).

Findings

By changing actuation parameters, the turbulence and mixing in the microchannel can be precisely varied to control the initiation of protein particle assembly while the solution conditions of assembly (pH and ionic strength) are kept constant. Importantly, mixing times as low as 6 ms can be achieved for triggering protein assembly in the microfluidic channel. In comparison to the conventional batch process of assembly, the acoustic microfluidic mixer approach produces smaller particles with a more uniform size distribution, promising a new way to manufacture protein particles with controllable quality.

假设

蛋白质纳米颗粒由于其广泛的应用而引起了人们的兴趣，这些广泛的应用范围从药物递送和疫苗到生物催化剂和生物传感器。纳米颗粒的形态和尺寸在确定其适用于不同应用方面起着至关重要的作用。然而，有效控制纳米颗粒的尺寸仍然是其制造中的重大挑战。本文的假设是，通过简单地改变混合时间和强度，同时保持化学参数不变，可以通过机械途径调节蛋白质颗粒的组装条件和大小。

实验性

我们使用声学驱动，高通量，超快，微流体混合器来组装大小可调的蛋白质颗粒。声学微混合器的性能通过激光多普勒振动测定法和图像处理来表征。蛋白质纳米颗粒的组装通过动态光散射（DLS）和透射电子显微镜（TEM）进行监控。

发现

通过更改驱动参数，可以精确改变微通道中的湍流和混合，以控制蛋白质颗粒组装的开始，同时使组装的溶液条件（pH和离子强度）保持恒定。重要的是，可以实现低至6 ms的混合时间，以触发微流体通道中的蛋白质组装。与传统的分批装配过程相比，声微流体混合器方法可产生尺寸更均一的较小颗粒，这有望成为一种制造质量可控的蛋白质颗粒的新方法。