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，包括高度本地化的药物输送，癌症治疗，如热疗和近距离治疗，微创手术和细胞运输。例如，微型游泳机器人是一种微小的机器，可以在人体血管内或组织间液中游泳，以执行生物医学手术。微型机器人在医学上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。磁致动仍然是无系绳驱动和控制微型机器人最实用的方法，因为它为移动传递动力，并为交付提供指导。然而，到目前为止，磁性微型机器人还不能提供足够的功能来完成预期的任务，例如，缺乏感知环境、做出实时决策和诱导预期变化的能力。此外，当控制一组微型机器人时，磁性驱动的有效性和灵活性急剧下降，因为磁性驱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非常复杂。此外，人工微型机器人缺乏感知同伴在群体中的地位的能力。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，应该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，由于其几个优点，为微/纳米尺度的货物运输提供了一种新的策略。这些细菌体积小，游动速度快，并包含一个传感器和执行器系统，可以自动对环境刺激做出反应。生物微机器人系统的可行性在最近的工作中得到了研究。例如，载药微粒附着在细菌上并被驱动到目标位置。我们首次提出了一个由磁性微型机器人（“主人”）和细菌群（“追随者”）组成的生物混合系统，以受益于细菌的微妙感觉系统以及它们的集体运动和合成微型机器人的精确磁导航。在这个系统中，一个磁性合成游泳者被一种化学物质激活，并被控制以触发细菌的战术反应。由于这种策略反应，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输送药物。本研究克服了孤立人工微机器人功能和交流能力不足、人工微机器人群体控制面临的挑战以及细菌导航的不稳定性和不准确性等问题。基于趋化性和光性的细菌运动响应精确控制的微型机器人创造了一个平台，它可以携带大量的货物，并具有更敏感的局部感知，如生化和光，以达到特定的微环境，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建一个可靠的微工程系统，该系统具有多种功能，包括推进、传感、制导、货物运输和操作，从而使微/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.