Printable Micro-rockets for Rapid Medical Diagnosis and Biomarker Detection

在高通量、时间紧迫的NHS医院实验室进行的医学诊断测试是确保临床医生能够提供高质量患者护理的关键。免疫分析是一种重要的检测方法，可以诊断各种各样的疾病，包括癌症和心脏病。这些检测是基于自然界的精密识别装置：抗体。免疫测定包括将抗体附着在检测器表面，等待感兴趣的分析物（如蛋白质生物标志物或特定细胞）在表面结合，最后使用电或光学方法读出测试结果。然而，由于许多诊断分析物的浓度很低，等待足够量的分析物扩散到检测器以实现读出所花费的时间可能很长。这些长孵育时间的后果是严重的：例如，每小时可以处理数千个样本的自动化医院仪器，在免疫测定过程完成之前的等待时间最多为20分钟。除了降低常规分析的吞吐量外，这些延迟还阻碍了向临床医生返回关键诊断信息的任务，例如胸痛患者的心脏问题筛查。抗体检测器中分析物的缓慢积累也限制了依赖于分离稀有细胞的方法的发展，例如循环肿瘤细胞，以指示癌症的进展并实现个性化医疗。在这种情况下，很明显，加快分析物到达检测器的速度是一个巨大的挑战，成功实现这一目标可以对医疗保健产生重大影响。在这里，我们提出了一种利用微火箭来实现快速分析物检测的新方法；能在流体中产生快速运动的小型装置。微型火箭的动力来自于表面不对称的气泡释放。这些气泡是由酶分解周围溶液中的燃料分子产生的。微型火箭将通过两种方式加快免疫分析的速度。首先，微火箭的快速运动和气泡产生解决了小尺度难以实现的问题。这将用于减少免疫测定的孵育时间，其中抗体附着在含有分析溶液的“微孔”的内表面。通过用微型火箭搅拌溶液，分析物将更频繁地接触井表面，从而加快检测速度。在第二种方法中，微型火箭本身将被抗体覆盖，并用作移动探测器，在整个分析样品中快速移动。快速运动将允许稀释量的分析物快速定位。通过使用快速移动的检测器表面，分析物与抗体的结合率和选择性也将得到提高。在孵育期结束时，将使用磁铁回收分散的火箭，以便使用现有的光学或电学方法确定分析物浓度。利用喷墨打印技术，可以轻松地控制和优化微型火箭的组成、大小和形状，从而有效地开发具有分析物识别和磁控制所需功能的新型微型火箭。为了证明微型火箭的效用，将进行实验，将微型火箭获取分析物的速度与医院使用的现有诊断方法进行比较。两种诊断测试将被考虑：一种是检测被称为“肌钙蛋白”的蛋白质分子，它表明最近的心脏损伤，另一种是检测循环肿瘤细胞。以这种方式证明微型火箭的有效性，将是吸引工业伙伴的兴趣的关键步骤，这些伙伴可以协助开发这项技术，以便最终在医院部署。

Medical diagnostic tests performed in high throughput, time critical NHS hospital laboratories are key to ensuring that clinicians can deliver high quality patient care. An important type of test, providing diagnosis for a wide range of diseases and illnesses, including cancer and heart problems, are immunoassays. These assays are based on nature's exquisite recognition apparatus: anti-bodies. Immunoassays involve attaching anti-bodies to a detector surface, waiting for the analyte (e.g. protein biomarkers or specific cells) of interest to become bound at the surface, and finally using electrical or optical methods to read-out the test result. However, due to the low concentration of many diagnostic analytes, the time spent waiting for sufficient amounts of analyte to diffuse to the detector to enable read-out can be significant. The consequence of these long incubation times is severe: for example automated hospital instruments that can handle thousands of samples per hour are rate limited by up to twenty minute waits for the immunoassay process to complete. As well as reducing throughput for routine analysis, these delays hamper the task of returning time critical diagnostic information to clinicians, such as screening for heart problems in patients with chest pain. Slow accumulation of analyte at an anti-body detector also limits developing methods that rely on isolating rare cells, such as circulating tumour cells to indicate the progression of cancer and enable personalised medicine.In this context, it is clear that the challenge of speeding up the rate at which analytes reach the detector is great, and that successfully achieving this can have significant Healthcare impact.Here we propose to develop a new approach to achieve rapid analyte detection, by exploiting micro-rockets; small scale devices that can generate rapid motion within fluids. Micro-rockets are powered by the asymmetrical release of bubbles from their surface. These bubbles are generated by enzymes decomposing fuel molecules in the surrounding solution. Micro-rockets will be used to speed up immunoassays in two ways. Firstly, micro-rockets' rapid motion and bubble generation stirs solutions, which is otherwise hard to achieve at small scales. This will be used to reduce the incubation times for immunoassays where anti-bodies are attached to the inside surfaces of a "micro-well" containing the analytical solution. By agitating the solution with micro-rockets, analytes will contact the well surfaces more frequently, speeding up detection. In the second method, the micro-rockets themselves will be covered with anti-bodies and used as a mobile detector, rapidly moving throughout the analytical sample. The fast motion will allow dilute quantities of analyte to be rapidly located. Analyte binding rate to anti-bodies and selectivity will also be improved by using a rapidly moving detector surface. At the end of the incubation period, magnets will be used to retrieve the dispersed rockets to enable analyte concentration to be determined using existing optical or electrical methods. Efficiently developing new micro-rockets with the required functions of analyte recognition and magnetic control will be aided by using ink-jet printing to allow micro-rocket composition, size, shape to be easily controlled and optimised.To demonstrate the utility of micro-rockets, experiments will be conducted to compare the speed at which micro-rockets can acquire analytes, compared to the existing diagnostic methods used by hospitals. Two diagnostic tests will be considered: one for protein molecules called "Troponins" that signal recent cardiac damage, and the second for circulating tumour cells. Establishing proof of micro-rocket effectiveness in this way will be a key step to attract interest from industrial partners who can assist the development of this technology to allow eventual deployment in hospitals.