Developing a prototype device for point-of-care non-alcoholic fatty liver disease diagnostics

非酒精性脂肪性肝病（NAFLD）是由肝脏中的脂肪积累引起的，影响全球20-30%的成年人，其中约20%的人进展为更严重的非酒精性脂肪性肝炎（NASH）。NASH相关的肝损伤是可逆的，但只有在早期诊断时才能逆转。然而，NASH的诊断率极低，并且对于大多数患者来说，诊断发生得太晚而无法进行干预。需要新的检测方法，允许更多的患者接受NASH检测，从而实现早期诊断和治疗。鉴于NASH很常见，这些测试理想情况下需要由GP提供，因此必须低成本且需要很少的设备。现有的测试和开发中的测试不符合这些要求，需要创新的方法来填补这一空白。该提案使用Rosa Biotech的传感平台Pandra来满足这一需求，该平台可以高精度地检测患者血液样本中的NASH。潘德拉利用嗅觉原理检测疾病。嗅觉系统使用蛋白质受体阵列，这些受体在气味进入鼻子时与气味结合。大脑识别受体刺激的模式，并将该模式解释为气味。当应用于生物传感时，该原理被称为差分传感。它允许分析样品总含量的微小变化，而不依赖于预先识别的疾病标志物。Rosa的传感技术Pandra使用的不是具有挑战性的嗅觉受体，而是结合有色染料的设计蛋白质阵列。将阵列暴露于含有脂肪的样品会在不同程度上取代蛋白质中的染料，从而导致整个阵列的颜色变化。这产生了样品的唯一“指纹”。人工智能（AI）算法被训练来识别已知样本中与疾病相关的指纹之间的差异。然后，该算法用于检测未知样本中的疾病。Pandra生产成本低，非专业人士也可以使用，对脂肪成分的微小变化很敏感。这使得它非常适合NASH诊断。该项目旨在生产一种早期原型Pandra传感器，可以部署在全科医生手术的护理点。这将为临床医生提供一个宝贵的新工具，用于初步评估NASH的高风险患者并决定最佳转诊途径。最终，它将产生一种新的测试，使更多的患者能够接受NASH测试，减少进展为更严重的肝脏疾病，癌症和死亡的人数。

Non-alcoholic fatty liver disease (NAFLD) is caused by fat accumulation in the liver and affects 20-30% of adults globally, ˜20% of whom progress to a more serious condition called non-alcoholic steatohepatitis (NASH). NASH-related liver damage is reversible, but only if diagnosed early. However, NASH diagnosis rates are extremely low, and for most patients diagnosis occurs too late for intervention. New tests are needed that allow more patients to be tested for NASH, resulting in earlier diagnosis and treatment. Given that NASH is common, these tests ideally need to be provided by a GP and, therefore, must be low-cost and require little equipment. Existing tests and those in development do not meet these requirements, and there is a need for innovative approaches that fill this gap.This proposal addresses this need using Rosa Biotech's sensing platform, Pandra, which can detect NASH in patient blood samples with high accuracy. Pandra detects disease using the principle of olfaction (the sense of smell). The olfactory system uses arrays of protein receptors that bind to odorants as they enter the nose. The brain recognises patterns of receptor stimulation and interprets the pattern as a smell. When applied to biosensing, this principle is called differential sensing. It allows small changes in a sample's total contents to be analysed, without relying on pre-identified markers of disease.Rather than olfactory receptors, which are challenging to work with, Rosa's sensing technology, Pandra, uses arrays of designed proteins that bind coloured dyes. Exposing the array to samples containing fats displaces the dyes from the proteins to different extents, resulting in colour changes across the array. This produces a unique 'fingerprint' for the sample. An artificial intelligence (AI) algorithm is trained to recognise differences between fingerprints associated with disease in known samples. The algorithm is then used to detect disease in unknown samples. Pandra is cheap to produce, usable by non-experts, and sensitive to small changes in fat composition. This makes it well-suited to NASH diagnostics.This project aims to produce an early prototype Pandra sensor that could be deployed at the point-of-care in a GPs surgery. This would provide clinicians with an invaluable new tool for initially assessing high-risk patients for NASH and deciding the best referral route. Ultimately, it will result in a new test that will enable more patients to be tested for NASH, reducing the number progressing to more severe liver disease, cancer, and death.