Usurping the scalpel: non-invasive oxygen nanosensors to refine data acquisition

测量细胞和组织内的氧气对于我们理解许多疾病的发展、进展和治疗至关重要，这些疾病包括心脏病、肺病、中风、多发性硬化症、糖尿病视网膜病变、血管闭塞和癌症。然而，测量人体氧气的方法在其适用性方面受到限制。因此，生物医学研究人员依靠动物研究来研究细胞和组织内的氧水平。然而，生物医学研究人员使用需要动物牺牲的技术仍然很常见。因此，在疾病发展的生物医学研究中，大量的动物被牺牲，而每只动物提供的数据相对较少。本研究的目的是开发一种有效的非侵入性技术，以可重复的方式在较长的时间内研究实验室动物的血液，细胞和组织中的氧气。通过“篡夺手术刀”，这项技术将有许多好处，包括减少科学研究中的动物牺牲，降低研究成本，并为生物医学研究人员提供更好的数据。该奖学金将开发纳米传感器，使用细胞友好的近红外光非侵入性地报告组织深处的氧气水平。纳米传感器将围绕一种被称为上转换纳米颗粒的纳米级晶体形成，当受到近红外光刺激时，它会发出红光。这些光学特性允许来自几十个纳米传感器的光通过几厘米的覆盖组织进行测量。这种组织通常必须通过手术切除，以便用传统的光学探针进行成像，动物可能在手术后被处死。纳米传感器将被构造成使得红光发射的强度在氧气存在的情况下发生变化：实际上，它们将充当由局部氧气水平控制的光学调光开关。通过用适当的生物识别分子修饰纳米传感器的表面，纳米传感器将被引导并锚定到感兴趣的细胞和组织上。此外，可以修改纳米传感器以确保它们对细胞无害。这些纳米传感器将在血液、细胞、细菌以及模拟活体动物组织的人造结构中进行测试。将进行测试，以确保纳米传感器对pH值，温度，溶解气体和组织色素沉着等变量具有鲁棒性。这项测试将证明纳米传感器适合在活体动物体内部署。这项工作将为与商业和学术合作伙伴合作开发氧气纳米传感器铺平道路。将纳米传感器技术传播给生物医学最终用户将减少生物医学研究中牺牲的动物数量，在降低研究成本、减少时间负担和提高数据质量方面提供额外的好处。这将为英国经济增加价值，并有助于实现英国政府在科学研究中减少动物牺牲的战略目标。

Measuring oxygen within cells and tissue is fundamentally important for our understanding of the development, progression, and therapy of many diseases, including heart disease, lung disease, stroke, multiple sclerosis, diabetic retinopathy, vessel occlusion, and cancer. However, methods to measure oxygen in humans are limited in their applicability. Therefore, biomedical researchers rely upon animal research to investigate oxygen levels within cells and tissue. However, it is still common for biomedical researchers to use techniques that necessitate animal sacrifice. Consequently, large numbers of animals are sacrificed in biomedical studies of disease development, with each animal providing a relatively sparse amount of data.The aim of this research is to develop an effective non-invasive technology to study oxygen within blood, cells and tissue of laboratory animals in a repeatable manner over extended time-periods. By "usurping the scalpel", this technology will have many benefits, including reducing animal sacrifice in scientific research, reducing the cost of research, and providing better data to biomedical researchers.This fellowship will develop nanosensors to non-invasively report oxygen levels deep within tissue using cell-friendly near-infrared light. The nanosensors will be formed around a nanoscale crystal known as an upconversion nanoparticle, which emits red light when stimulated by near infrared light. These optical properties allow light from a just a few dozen of these nanosensors to be measured through several centimetres of overly tissue. Such tissue would normally have to be surgically removed for imaging with conventional optical probes, with the animal likely being sacrificed after the procedure. The nanosensors will be constructed so that the intensity of red-light emission changes in the presence of oxygen: in effect they will act as an optical dimmer switch controlled by localised oxygen levels. The nanosensors will be guided and anchored to cells and tissues of interest by modifying their surface with appropriate biorecognition molecules. Further, the nanosensors can be modified to ensure that they are not harmful to cells. The nanosensors will be tested in blood, within cells, within bacteria, and within artificial constructs called phantoms, which will simulate the tissue of living animals. Testing will be conducted to ensure that the nanosensors are robust against variables such as pH, temperature, dissolved gases, and tissue pigmentation. This testing will demonstrate that the nanosensors are fit for deployment within living animals.This work will pave the way for the oxygen nanosensors to be developed in collaboration with commercial and academic partners. Dissemination of the nanosensor technology to biomedical end-users will reduce the number of animals sacrificed in biomedical research, providing additional benefits in reduced costs for research, reduced time-burdens, and improved data quality. This will add value to the UK economy and help meet the UK government's strategic aim of reducing animal sacrifice in scientific research.