21ENGBIO-THE TRANSDUCING ANALYTICAL BIOSYSTEM (TABS): A PLATFORM FOR DIAGNOSTICS (TABS-DX)

在Covid之前，生物传感器的全球市场规模为420亿美元，预计未来60年将翻一番，仍由临床诊断和疾病管理主导，需要以更低成本进行早期检测的新技术。新冠肺炎检测使体外诊断(IVDS)成为一种家喻户晓的产品，但IVDS不仅有望在更快地识别病原体和遏制传染病方面发挥作用，而且还需要对急慢性疾病的治疗和管理，使之能够通过适当的治疗进行早期诊断，改善患者预后。新生儿和儿科对半胱氨酸氨基转移酶C(CysC)作为急性肾功能的标志物以及发病率和死亡率的预测因子很感兴趣。它是一个比通常使用的肌酐更早的指标，尤其适用于儿科/新生儿和重症监护中的肾功能评估，在这些情况下，肾小球滤过率GFR的急剧波动和对早期肾损伤缺乏肌酐敏感性会使儿童面临抗生素中毒的风险。许多用于医学诊断的生物分析试剂是酶、抗体、多肽等，它们都是从自然中提取的，大多采用发酵技术生产。然而，它们不是本质上智能的材料；即它们通常不会产生分析信号，而无需进一步(化学)修改生物分析试剂或添加化学指示剂即可测量。额外的制造成本和化学试剂显著增加了成本，并降低了发酵生产的“绿色”影响。这也意味着，小体积生物标记物测量目标在商业上是不可行的。在这个项目中，我们将使用合成生物学来制造智能分析试剂：作为诊断平台的转导分析生物系统(TAB)(TABS-DX)。标签可以连接到纤维和颗粒上，使它们更易于使用和存储。将设计一种CysC护理点测试系统，并将试验一种新的真空打印技术，以沉积纤维或颗粒，以产生CysC的体外诊断原型，该原型将与儿科单位一起在临床研究中进行测试。

The world market for biosensors was $42Bn before Covid and is expected to double in the next 6yrs, still dominated by clinical diagnostics and disease management, demanding new technologies for early detection at lower cost. Covid-19 testing made in vitro diagnostics (IVDs) a household product, but IVDs are not only expected to play their part in faster identification of causative pathogens and containment of infectious disease, but there is also a need in treatment and management in acute and chronic disease, enabling earlier diagnosis with appropriate treatment, improving patient outcomes. There is interest from neonatal and paediatric units in Cystatin C (CysC) as a marker of acute renal function, as well as a predictor of morbidity and mortality. It is a much earlier indicator than the normally used creatinine and is particularly attractive for assessing kidney function in paediatrics/neonatology and intensive care, where acute fluctuations in glomerular filtration rate GFR and lack of creatinine sensitivity to incipient renal impairment puts children at risk from antibiotic toxicity. Many bioanalytical reagents for medical diagnostics are enzymes, antibodies, peptides etc. They are derived from nature and mostly produced by fermentation techniques. However, they aren't intrinsically smart materials; ie they don't usually yield an analytical signal that can be measured without further (chemical) modification of the bioanalytical reagent or addition of chemical indicators. The additional manufacturing costs and chemical reagents adds significant cost and reduces the 'green' impact of the manufacturing by fermentation. It also means that small volume biomarker measurement targets do not become commercially viable. It needs 'blockbuster' targets like glucose monitoring for diabetics to be an attractive commercial investment.In this project we will use synthetic biology to make smart analytical reagents: the TRANSDUCING ANALYTICAL BIOSYSTEM (TABS) as a platform for diagnostics (TABS-DX). The TABS can be attached to fibres and particles, making them easier to use and to store. A CysC point of care test system will be designed and a novel vacuum printing technique will be trialed to deposit the fibres or particles to produce prototype in vitro diagnostics for CysC, which will be tested in a clinical study, with the paediatrics unit.