Microfluidic systems for high efficiency radiolabeling and purification of nanomedicines

研究疾病途径或诊断疾病的一种方法是使用单光子发射计算机断层扫描（SPECT）成像。使用SPECT，发射伽马射线的放射性同位素连接到分子，大分子化合物或纳米到微米范围内的化合物中。大多数情况下，这个放射性标记步骤是使用试剂盒格式完成的，其中将放射性添加到所有其他成分的小瓶中，以快速获得放射性标记的化合物，然后将该化合物注射到动物或患者体内。然而，不能总是使用试剂盒格式，因为引入放射性同位素可能会改变最终放射性标记化合物的性质，或者系统的化学性质可能不允许有效的放射性标记程序（需要多个步骤，辐射危害，空气敏感，需要分离步骤）。本项目旨在建立一个微流体微/纳米装置，以克服放射性药物的放射性标记和纯化困难，包括纳米颗粒、微球和大分子化合物。我们将仔细整合微流体通道内的放射性标记步骤，这将优化扩散和反应动力学。如果有必要，我们还将在内置混合结构上应用强制混合，使用内置可加热反应器功能，并根据我们在该领域的最新研究，利用微流控迪安力浓缩和分离所得化合物和纳米药物。另一个分离特性可能是利用局部磁力。目的是提高程序的便利性和放射性标签效率，同时允许理想的无菌条件和易于质量控制。由此产生的放射性药物将在材料使用（假设要少得多）、反应时间（可能更短）和放射性标记效率（可能更高）方面与传统技术进行比较。不同的放射性同位素系统将被研究，以铼为基础的系统（例如Re-188）为前沿。目前，它们的氧化敏感性（回到水溶性过透酸盐）是一个问题，并将为未来的治疗应用进行优化。因此，用于制备诊断和治疗放射性药物的基于微流控的方法可能对允许足够高的辐射浓度至关重要，并为未来的癌症检测和治疗提供真正的治疗剂。

One method of investigating disease pathways or diagnosing diseases is imaging using single photon emission computed tomography (SPECT). With SPECT, a gamma-emitting radioisotope is connected to or incorporated into a molecule, a macromolecular compound, or a compound in the nano- to micro-meter range. Most often, this radiolabeling step is accomplished using a kit format, where the radioactivity is added to a vial of all the other ingredients to quickly obtain the radiolabeled compound and this compound is then injected into an animal or patient. The kit format, however, cannot always be used, as the introduction of the radioisotope might change the properties of the final radiolabeled compound, or the chemistry of the system might not allow for an efficient radiolabeling procedure (multiple steps required, radiation hazard, air sensitive, separation steps needed). This project aims to build a microfluidics micro-/nanodevice to overcome difficulties of radiolabeling and purifying radiopharmaceuticals that include nanoparticles, microspheres, and macromolecular compounds. We will carefully integrate the radiolabeling step inside microfluidic channels, which will be optimized for diffusion and reaction kinetics. We will also, if necessary, apply forced mixing on built-in mixing structures, use a built-in heatable reactor feature, and concentrate and separate the resulting compounds and nanomedicines with microfluidic Dean forces, based on our recent research in this field. An additional separation feature might be the use of local magnetic forces. The aim is to improve on the ease of procedure and the radiolabeling efficiency, while at the same time allowing for ideally aseptic conditions and ease of quality control. The resulting radiopharmaceuticals will be compared to the conventional techniques in terms of material use (which is hypothesized to be much less), reaction time (likely shorter), and radiolabeling efficiency (likely higher). Different radioisotope systems will be investigated, with rhenium-based ones (for example Re-188) being at the forefront. Currently, their oxidation sensitivity (back to water soluble perrhenate) is a problem, and will be optimized for future therapeutic applications. Microfluidic based methods for the preparation of diagnostic and therapeutic radiopharmaceuticals might thus be crucial to allow for high enough radiation concentrations, and provide truly theranostic agents for future detection and treatment of cancer.