Supplement: Bio CaRGOS: Capture and release gels for optimized storage of Cancer Biospecimens

补充：Bio CaRGOS：捕获和释放凝胶以优化癌症生物样本的储存

• 批准号: 10381281
• 负责人: Gautam Gupta
• 金额: $ 3.5万
• 依托单位: UNIVERSITY OF LOUISVILLE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10381281
• 关键词: Achievement; Albumins; Amylases; Antigens; Area; Biological Markers; Buffers; Cancer Model; Cell Line; Chemical Engineering; Clinical; Complex; Cryopreservation; Detection; Diagnosis; Disease; Doctor of Philosophy; Due Process; Early Diagnosis; Electrolytes; Engineering; Equipment; Experimental Designs; Fibrinogen; Formulation; Freezing; Future; Gel; Globulins; Glucose; Goals; Grant; Immunoassay; Individual; Ionic Strengths; Malignant Neoplasms; Malignant neoplasm of pancreas; Measures; Methanol; Methodology; Methods; Modeling; Monitor; Nature; Patient Monitoring; Performance; Pharmaceutical Preparations; Pharmacologic Substance; Phosphate Buffer; Physiological; Plasma; Plasma Proteins; Play; Polymerase Chain Reaction; Process; Property; Proteins; Protocols documentation; RNA vaccine; Recovery; Recurrence; Reproducibility; Research; Research Personnel; Reverse Transcription; Role; Saline; Sampling; Silicon Dioxide; Students; Techniques; Technology; Temperature; Time; Uric Acid; Virus; Work; anticancer research; aqueous; base; biomaterial compatibility; cancer biomarkers; cost; digital; innovation; insight; interest; microwave electromagnetic radiation; parent grant; preservation; skills; solute; specific biomarkers; undergraduate student; user-friendly

Biomarkers play a central role in the detection, diagnosis, management and monitoring of patients with cancer. Factors such as analytical sensitivity and reproducibility are critical to the clinical utility of plasma-based biomarkers in the setting of longitudinal surveillance and early detection of disease and or recurrence. Currently, the state of preservation of biospecimens is accomplished primarily using sub freezer techniques and it is cost prohibitive and certainly not practical in most scenarios. There is clearly a dearth of techniques that can preserve the biospecimens at room temperature for long periods of time. Therefore, there is a critical unmet clinical need for storing a plethora of biospecimens acquired routinely. In the parent grant, we proposed to demonstrate stability and integrity of Pancreatic Cancer Specific biomarkers (CA-A19, miRNA21, and ctDNA) in buffers as well as plasma for extended periods of time at room temperature utilizing a 1-step microwave based sol-gel process. The specific aims were: The specific aims of this research were: (A) Achieve complete integrity and stability of cancer biomarkers in physiologic electrolytes at room temperature. (B) Demonstrate integrity and stability of cancer biomarkers in presence the major plasma proteins (albumin, globulin and fibrinogen). (C) Investigate the integrity of induced cancer biomarkers and native biomarkers present in plasma Solutes such as glucose, uric acid, and other nominal proteins can have an effect on CaRGOS. In the Supplement Grant, Lindsay will develop a reverse engineering approach and will work closely with the PIs and students to directly stabilize biomarkers in plasma. Lindsay started working on this approach and have observed critical challenges including: (i) biocompatibility of the process due to even minimal presence of methanol (ii) possible interference of silica with characterization techniques such as dd PCR. (iii) intensive extraction protocols for extraction of biomarkers from plasma and their compatibility with the silica. These three major hurdles form the basis of the supplement grant, where we will need to advance our fundamental understanding of the nature of interactions of silica precursors with a complex matrix such as plasma. The specific aims of the Supplement grant are: (A) Elimination of methanol from the precursor sol prior to addition of biomarker/plasma. (B) Develop robust protocols to separate silica from the biomarkers at the point of downstream processing During the first year, Lindsay will be an undergraduate researcher and obtain her B.S. in Chemical Engineering. During the second year she will obtain her master’s in engineering enabling her to enrich her skill set in this area. This focused project will allow Lindsay to become an independent and confident researcher in future that aligns with her goals to obtain a MD/PhD.

生物标志物在患者的检测、诊断、管理和监测中发挥着核心作用 得了癌症分析灵敏度和重现性等因素对临床分析至关重要。 基于血浆的生物标志物在纵向监测和早期检测中的实用性 疾病或复发。目前，生物标本的保存状态已经完成， 主要使用亚冷冻器技术，成本过高，在大多数情况下当然不实用， 场景很明显，目前缺乏在室内保存生物标本的技术。 温度长时间。因此，对于储存一种药物存在关键的未满足的临床需求。 大量的生物样本 在母基金中，我们提议证明胰腺癌的稳定性和完整性， 缓冲液以及血浆中的特异性生物标志物（CA-A19、miRNA 21和ctDNA），用于延长 在室温下使用1-步基于微波的溶胶-凝胶法。的 具体目标是： 本研究的具体目标是：（A）实现癌症的完全完整性和稳定性 生理电解质中的生物标志物。(B)展示诚信和稳定 在主要血浆蛋白（白蛋白、球蛋白和纤维蛋白原）存在的情况下，癌症生物标志物。（丙） 研究诱导的癌症生物标志物和血浆中存在的天然生物标志物的完整性 诸如葡萄糖、尿酸和其他标称蛋白质的溶质可以对CaRGOS具有影响。 在补助金，林赛将开发一个逆向工程的方法，将工作 与PI和学生密切合作，直接稳定血浆中的生物标志物。林赛开始工作 并观察到关键挑战，包括：（i）工艺的生物相容性 由于甚至最小的甲醇存在（ii）二氧化硅对表征的可能干扰 技术，如ddPCR。(iii)用于提取生物标志物的密集提取方案 等离子体及其与二氧化硅的相容性。这三个主要障碍构成了 补充补助金，在那里我们需要推进我们的基本理解的性质， 二氧化硅前体与复杂基质如等离子体的相互作用。的具体目标 补充补助金为： (A)在添加生物标志物/血浆之前从前体溶胶中消除甲醇。（B） 开发可靠的方案，在下游点将二氧化硅与生物标志物分离 处理 在第一年，林赛将是一个本科研究员，并获得学士学位。化学 工程.在第二年，她将获得工程硕士学位，使她能够 丰富她在这方面的技能。这个重点项目将使林赛成为一个独立的 和自信的研究人员在未来，符合她的目标，以获得MD/博士学位。