Development of a biohybrid microrobotic system: Future drug delivery

微型机器人系统有可能在许多应用中彻底改变医学和治疗，包括高度局部化的药物递送、癌症治疗，如热疗和近距离放射治疗、微创手术和细胞运输。例如，游泳微型机器人是一种微小的机器，它在人体的血管内或组织间液中游泳，以执行生物医学操作。微型机器人在医学中的应用需要多学科的细致研究。目前开发自主系统的一个挑战是为微型机器人提供动力和控制。磁致动仍然是最实用的方式为无绳供电和控制的微型机器人，因为它传递动力的运动，并使指导交付。然而，到目前为止，磁性微型机器人提供的功能不足以完成可预见的任务，例如，缺乏感知环境，做出实时决策和诱导所需变化的能力。此外，在控制微型机器人团队时，磁致动的有效性和灵活性急剧下降，因为磁致动为团队中的所有设备提供了相同的驱动力，这使得单个机器人的控制变得非常复杂。此外，人造微型机器人缺乏感知其配偶在群体中地位的能力。单个微型机器人携带的药物量不足以进行有效的治疗，因此，需要使用大量的微型机器人。或者，利用微生物，特别是细菌，作为智能微型机器人，由于它们的几个优点，为微/纳米级的货物递送提供了一种新的策略。这些细菌体积小，游动速度快，包含一个传感器和致动器系统，可以自动响应环境刺激。生物微型机器人系统的可行性已经在最近的工作中进行了研究。例如，载药微粒已经附着到细菌上并被驱动到目标位置。我们提出，第一次，一个生物杂交系统组成的磁性microrobot（“主人”）和细菌（“追随者”）的群体受益于微妙的感觉系统的细菌沿着他们的集体运动和精确的磁性导航的合成microrobot。在这个系统中，磁性合成游泳者被化学物质功能化，并被控制以触发细菌的战术反应。由于这种战术反应，细菌被化学物质吸引。因此，微型机器人可以引导它们并将它们引导到目标位置以提供药物。这项研究克服了孤立的人工微机器人的功能和通信不足，人工微机器人群体控制的挑战，以及细菌作为生物微/纳米机器人导航的不稳定性和不准确性。细菌的趋化性和趋光性运动响应于精确控制的微型机器人创建了一个平台，该平台可以携带大体积的货物，并具有更灵敏的局部传感，如生化和光，以到达特定的微环境，从而在生物医学和纳米技术中执行复杂的应用。这项研究将有助于创造一个可靠的微工程系统，具有多种功能，包括推进，传感，引导，货物运输和操作，使微/纳米机器人技术更快地走向临床试验。

Microrobotic systems have the potential to revolutionise medicine and treatment in many applications including highly localized drug delivery, cancer therapies, such as hyperthermia and brachytherapy, minimally invasive surgery and cell transportation. Swimming microrobots, for example, are tiny machines that swim in the body's intravascular or interstitial fluids to perform biomedical operations. The application of microrobots in medicine requires a multidisciplinary delicate investigation. A current challenge in developing autonomous systems is to provide power and control for the microrobots. Magnetic actuation remains the most practical way for untethered powering and control of microrobots as it transfers power for movement and enables guidance for delivery. However, magnetic microrobots so far afford insufficient functionality to accomplish the foreseen tasks lacking, for example, the ability to sense their environment, make real-time decisions, and induce desired changes. Further, the effectiveness and flexibility of magnetic actuation drastically declines when controlling a team of microrobots since magnetic actuation provides an identical driving force for all devices in the team that makes the control of individual robots highly complicated. Additionally, the artificial microrobots lack the ability to sense the status of their mates in the group. The amount of medicine that can be carried by a single microrobot is not sufficient for an effective treatment, hence, a large group of microrobots should be utilised.Alternatively, harnessing microorganisms, especially bacteria, as intelligent tiny robots provides a novel strategy for cargo delivery at micro-/nanoscale owing to their several advantages. These bacteria have a small size, swim fast and contain a system of sensors and actuators that automatically responds to environmental stimuli. The feasibility of biomicrorobotic systems has been studied in recent works. For example, drug-loaded microparticles have been attached to bacteria and driven to the target position. We propose, for the first time, a biohybrid system composed of a magnetic microrobot (a "master") and groups of bacteria ("followers") to benefit from the subtle sensory system of bacteria along with their collective motility and precise magnetic navigation of the synthetic microrobot. In this system, a magnetic synthetic swimmer is functionalised with a chemical and controlled to trigger the tactic response of bacteria. The bacteria are attracted towards the chemical because of this tactic response. Therefore, the microrobot can lead them and direct them to a target position to deliver medicine. This research overcomes the insufficient functionality and communication of solitary artificial microrobots, challenges in artificial microrobotic swarm control, and instability and inaccuracy in the navigation of bacteria as bio micro/nanorobots. Chemotaxis and phototaxis-based motion of bacteria in response to the precisely controlled microrobot creates a platform, which can carry a large-volume cargo and have more sensitive local sensing such as biochemical and light to reach specific microenvironments to perform intricate applications in biomedicine and nanotechnology. This research would help efforts in creating a reliable microengineered system with multiple functions including propulsion, sensing, guidance, cargo delivery, and operation that move the micro/nanorobotics technology toward clinical trials more rapidly.