A novel Deep Raman spectroscopy platform for non-invasive in situ molecular analysis of disease specific tissue compositional changes.

一种新型深度拉曼光谱平台，用于对疾病特定组织成分变化进行非侵入性原位分子分析。

• 批准号: EP/K020374/1
• 负责人: Nicholas Stone
• 金额: $ 92.46万
• 依托单位: UNIVERSITY OF EXETER
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2013
• 资助国家: 英国
• 起止时间: 2013 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FK020374%2F1
• 关键词: novel; Deep; Raman; spectroscopy; platform

Recently, we have pioneered a portfolio of revolutionary optical technologies in the area of laser spectroscopy, namely deep Raman spectroscopy, for non-invasive molecular probing of biological tissue. The developments have the potential of making a step-change in many fields of medicine including cancer diagnosis. The techniques comprise spatially offset Raman spectroscopy (SORS) and Transmission Raman (both patented by the applicants). The methods are described in detail in a tutorial review: http://www.rsc.org/Publishing/Journals/CS/article.asp?doi=b614777c . There is an urgent clinical need for early objective diagnosis and prediction of likely treatment outcomes for many types of subsurface cancers. This is not addressed by existing technologies. There are numerous steps along the cancer clinical pathway where real-time, in vivo, molecular specific disease analysis would have a major impact. This would allow for more accurate and immediate diagnosis at first presentation, by improving screening or surveillance techniques, leading to earlier diagnosis and better treatment outcomes. Secondly it would allow surgical margin assessment and treatment monitoring in real-time and thirdly identification of metastatic invasion in the lymphatic system during routine surgery. There are numerous other areas where a rapid molecular analysis of a tissue sample in the clinic or theatre environment would allow improved clinical decision-making. Clearly these approaches would be beneficial to the patient by reducing cancer recurrence rates; but also by minimising the numbers of invasive procedures required, thus reducing costs and patient anxiety.Raman spectroscopy is a highly molecular-specific method, which itself has proven to be a useful tool in early epithelial cancer diagnostics, although it has been restricted to sampling the tissue surface of less than 1 mm deep. Our new technology unlocks unique access to tissue abnormalities of up to several cm's deep, i.e. at depths one to two orders of magnitude higher than those previously possible with conventional Raman. We propose to make major breakthroughs in this area and advance diagnostics (including cancer margin assessment and staging) particularly focussed on breast cancer and lymph node metastasis initially as focused case studies and then potentially applied to prostate cancers (not included directly in this proposal). This will be explored as a joint cross-disciplinary venture between Profs Stone and Matousek, the two key researchers in this area, who between them have pioneered the concepts and have established a team of cross-disciplinary scientists and clinicians to advance this field.To fully capitalise on our international lead, we now seek funding to progress this work in a timely manner by developing a novel medical diagnostic platform. We propose to bring together key players from multidisciplinary areas covering physical sciences, spectroscopy, radiology, cancer diagnostic and therapeutic surgery, and histopathology to exploit all of the relevant skills and develop a critical mass of researchers. The principal collaborating teams at the heart of the programme will include: 1) Matousek group in Central Laser Facility at Rutherford Appleton Laboratory focussing on maximising the potential of the technique by implementing further technological developments. 2) Stone group with 17 years experience of applied clinical spectroscopy to develop and evaluate the technology applied to human tissues and undertake complex multivariate analysis to distil the data into relevant diagnostic outputs.

最近，我们在激光光谱学领域开创了一系列革命性的光学技术，即深度拉曼光谱，用于生物组织的非侵入性分子探测。这些发展有可能在包括癌症诊断在内的许多医学领域产生重大变化。这些技术包括空间偏移拉曼光谱(SOR)和传输拉曼(均由申请人申请专利)。这些方法在教程评论中进行了详细描述：http://www.rsc.org/Publishing/Journals/CS/article.asp?doi=b614777c。临床上迫切需要对许多类型的亚表面下癌症进行早期客观诊断和预测可能的治疗结果。现有技术没有解决这一问题。在癌症临床路径上有许多步骤，实时的、活体的、分子特异性的疾病分析将产生重大影响。这将通过改进筛查或监测技术，在首次出现时实现更准确和更迅速的诊断，从而导致更早的诊断和更好的治疗结果。其次，它将使手术切缘评估和治疗实时监测，以及第三，在常规手术中识别淋巴系统的转移侵犯。还有许多其他领域，在诊所或剧院环境中对组织样本进行快速分子分析将有助于改进临床决策。显然，这些方法将通过降低癌症复发率而对患者有利；还通过最大限度地减少所需的侵入性手术的数量，从而降低成本和患者的焦虑。拉曼光谱是一种高度分子特异性的方法，其本身已被证明是在早期上皮癌诊断中的有用工具，尽管它被限制在对深度小于1毫米的组织表面进行采样。我们的新技术解锁了对深达几厘米的组织异常的独特访问，即深度比传统拉曼技术高一到两个数量级。我们建议在这一领域取得重大突破，推进诊断(包括癌症边缘评估和分期)，特别是最初以乳腺癌和淋巴转移为重点的病例研究，然后潜在地应用于前列腺癌(不直接包括在本提案中)。这将作为这一领域的两位关键研究人员斯通教授和马图塞克教授的联合跨学科项目进行探索，他们共同开创了这一概念，并建立了一支跨学科科学家和临床医生团队来推动该领域的发展。为了充分利用我们的国际领先地位，我们现在寻求资金，通过开发一个新的医疗诊断平台来及时推进这项工作。我们建议将来自多学科领域的关键参与者聚集在一起，包括物理科学、光谱学、放射学、癌症诊断和治疗外科以及组织病理学，以利用所有相关技能并培养一支关键的研究人员队伍。该计划核心的主要合作团队将包括：1)卢瑟福·阿普尔顿实验室中央激光设施的Matousek小组，专注于通过实施进一步的技术开发来最大限度地发挥技术的潜力。2)具有17年临床应用光谱学经验的Stone小组，开发和评估应用于人体组织的技术，并进行复杂的多变量分析，将数据提炼成相关的诊断输出。

项目成果

Noninvasive Determination of Depth in Transmission Raman Spectroscopy in Turbid Media Based on Sample Differential Transmittance

• DOI: 10.1021/acs.analchem.7b01469
• 发表时间: 2017-09-19
• 期刊: ANALYTICAL CHEMISTRY
• 影响因子: 7.4
• 作者: Gardner, Benjamin;Stone, Nicholas;Matousek, Pavel
• 通讯作者: Matousek, Pavel

Noninvasive simultaneous monitoring of pH and depth using surface-enhanced deep Raman spectroscopy

• DOI: 10.1002/jrs.5875
• 发表时间: 2020-03-20
• 期刊: JOURNAL OF RAMAN SPECTROSCOPY
• 影响因子: 2.5
• 作者: Gardner, Benjamin;Stone, Nicholas;Matousek, Pavel
• 通讯作者: Matousek, Pavel