A non-invasive nanotechnology-based skin patch for multiplexed diagnostics

基于纳米技术的非侵入性皮肤贴片，用于多重诊断

• 批准号: 8265831
• 负责人: Lance Allen Liotta
• 金额: $ 19.64万
• 依托单位: GEORGE MASON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-01 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8265831
• 关键词: Adhesives; Affinity; Albumins; Animal Model; Artificial nanoparticles; Binding; Biological; Biological Assay; Biological Markers; Biological Preservation; Calcitonin; Cavia; Chemicals; Chemistry; Clinical; Collection; Cystic Fibrosis; Detection; Devices; Diagnostic; Diagnostic tests; Disease; Drug Delivery Systems; Dyes; Electrolytes; Estradiol; Evaluation; Exclusion; FDA approved; Feasibility Studies; Female; Foundations; Grant; Harvest; Hour; Human; Human Volunteers; Hydrogels; IL8 gene; Immunoassay; Incubated; Institutional Review Boards; Interleukin-6; Interleukins; Iontophoresis; Liquid substance; Mails; Mass Spectrum Analysis; Measurement; Measures; Membrane; Modeling; Molecular Weight; Nanotechnology; New Zealand; One-Step dentin bonding system; Oryctolagus cuniculus; Particle Size; Patch Tests; Patients; Peptide Hydrolases; Peptides; Physiological; Process; Progesterone; Proteins; Running; Sampling; Screening procedure; Serum; Skin; Solutions; Source; Surface; Sweat; Sweating; TNF gene; Technology; Temperature; Testing; Testosterone; Textiles; Thick; Time; Toxic effect; Transudate; base; chemical release; disease diagnosis; eccrine; healthy volunteer; interest; male; nanoparticle; nervous system disorder; new technology; novel; particle; poly-N-isopropylacrylamide; prevent; protein metabolite; skin irritation; skin patch; uptake; volunteer

DESCRIPTION (provided by applicant): Sweat is an unexploited biological fluid that can provide a wealth of diagnostic information. We propose a novel technology to be used at the bedside or in the field: a diagnostic skin patch which harvests, concentrates, and stabilizes a panel of biomarkers derived from skin transudate or sweat. While drug delivery patches are routinely used, the technology proposed here has exactly the opposite function: the harvesting of diagnostic markers. Using mass spectrometry we have identified 228 proteins and peptides that were not previously known to exist in human sweat. In order to exploit this new class of analytes we propose to create novel affinity bait nanoparticles, bound within an adhesive skin patch. The proposed technology is transformative because it overcomes all the major physiological barriers that have prevented the use of this biologic fluid for diagnostic testing. Sweat disease biomarkers a) are subject to rapid degradation due to proteases present in sweat and normal skin bacterial flora, and b) exist in extremely low abundance, far below the detection sensitivity of standard analysis platforms. Harvesting hydrogel nanoparticles are engineered with chemical high affinity baits so that they sequester the low abundance target analytes, and protect them from degradation indefinitely. We propose to integrate the nanoparticles into the fabric of an adhesive skin patch. Once applied to the skin, the nanoparticles in the patch harvest minute by minute, and protect from degradation, all candidate analytes in the sweat underneath the patch. The core shell bait nanoparticles are a completely novel technology that can amplify the sensitivity of biomarker detection by 100 fold. No other technology exists that has a similar yield, concentration ability, and stabilization function. Once the collection is complete, the patch can simply be mailed to the diagnostic lab at room temperature. Upon receipt, the nanoparticle-captured analytes of interest can be eluted from the patch for routine measurement using any platform. Our feasibility studies demonstrate virtually 100 percent capture and 100 percent elution yield of low abundance interleukins in model sweat solutions. We will engineer the nanoparticles, and construct test patch devices. The test patches will be evaluated in animal models to verify lack of skin irritation. We will collect sweat from healthy volunteers under IRB approval using an FDA approved iontophoresis sampling device used for electrolyte measurement. We will apply the collected sweat to the novel nanoparticle patch ex vivo at the point of collection. Mass spectrometry will be used to discover novel sweat biomarkers that have been concentrated and preserved in the patch. Low abundance labile sweat biomarkers harvested from the nanoparticles will be measured by clinical immunoassays to verify sensitivity and precision. The derived list of eccrine sweat proteins will be an important deliverable as a foundation for the general field of sweat biomarker testing. The technology is especially suited to the evaluation of neurological disorders as it is non invasive and would be fully acceptable as a routine screening procedure.

描述（由申请人提供）：汗液是一种未开发的生物液体，可提供丰富的诊断信息。我们提出了一种用于床边或现场的新技术：一种诊断皮肤贴片，它可以收集、浓缩和稳定一组来自皮肤渗出液或汗液的生物标志物。虽然药物递送贴片是常规使用的，但这里提出的技术具有完全相反的功能：诊断标记物的收获。使用质谱分析，我们已经确定了228种蛋白质和肽，这些蛋白质和肽以前不知道存在于人类汗液中。为了利用这类新的分析物，我们建议创建新的亲和诱饵纳米颗粒，粘合剂皮肤贴片内绑定。所提出的技术是变革性的，因为它克服了所有主要的生理障碍，这些障碍阻碍了这种生物液体用于诊断测试。汗液疾病生物标志物a）由于汗液和正常皮肤细菌植物群中存在的蛋白酶而经历快速降解，和B）以极低的丰度存在，远低于标准分析平台的检测灵敏度。收获水凝胶纳米颗粒用化学高亲和力诱饵进行工程化，使得它们螯合低丰度目标分析物，并保护它们不被无限期降解。我们建议将纳米颗粒整合到粘性皮肤贴片的织物中。一旦应用到皮肤上，贴片中的纳米颗粒每分钟都在收集，并保护贴片下方汗液中的所有候选分析物免受降解。核壳诱饵纳米颗粒是一种全新的技术，可以将生物标志物检测的灵敏度提高100倍。不存在具有类似产率、浓缩能力和稳定功能的其他技术。一旦收集完成，补丁可以简单地在室温下邮寄到诊断实验室。在接收时，纳米颗粒捕获的感兴趣的分析物可以从贴片洗脱，用于使用任何平台进行常规测量。我们的可行性研究表明，几乎100%的捕获和100%的洗脱率低丰度白细胞介素在模型汗液解决方案。我们将设计纳米粒子，并构建测试贴片设备。将在动物模型中评价供试贴剂，以验证无皮肤刺激。我们将在IRB批准下使用FDA批准的用于电解质测量的离子电渗采样装置收集健康志愿者的汗液。我们将在收集点将收集的汗液应用于离体的新型纳米颗粒贴片。质谱法将用于发现新的汗液生物标志物，这些生物标志物已被浓缩并保存在贴片中。将通过临床免疫测定来测量从纳米颗粒收集的低丰度不稳定汗液生物标志物，以验证灵敏度和精确度。外分泌汗液蛋白的衍生列表将成为汗液生物标志物测试一般领域的基础。该技术特别适合于神经系统疾病的评估，因为它是非侵入性的，并且作为常规筛查程序是完全可以接受的。

项目成果

Unlocking the secrets to protein-protein interface drug targets using structural mass spectrometry techniques.

使用结构质谱技术解开蛋白质-蛋白质界面药物靶点的秘密。

• DOI: 10.1586/14789450.2015.1079487
• 发表时间: 2015
• 期刊: Expert review of proteomics
• 影响因子: 3.4
• 作者: Dailing,Angela;Luchini,Alessandra;Liotta,Lance
• 通讯作者: Liotta,Lance

Application of Nanotrap technology for high sensitivity measurement of urinary outer surface protein A carboxyl-terminus domain in early stage Lyme borreliosis.

• DOI: 10.1186/s12967-015-0701-z
• 发表时间: 2015-11-04
• 期刊: Journal of translational medicine
• 影响因子: 7.4
• 作者: Magni R;Espina BH;Shah K;Lepene B;Mayuga C;Douglas TA;Espina V;Rucker S;Dunlap R;Petricoin EF;Kilavos MF;Poretz DM;Irwin GR;Shor SM;Liotta LA;Luchini A
• 通讯作者: Luchini A

Proteomic analysis of eccrine sweat: implications for the discovery of schizophrenia biomarker proteins.

• DOI: 10.1021/pr2007957
• 发表时间: 2012-04-06
• 期刊: Journal of proteome research
• 影响因子: 4.4
• 作者: Raiszadeh MM;Ross MM;Russo PS;Schaepper MA;Zhou W;Deng J;Ng D;Dickson A;Dickson C;Strom M;Osorio C;Soeprono T;Wulfkuhle JD;Petricoin EF;Liotta LA;Kirsch WM
• 通讯作者: Kirsch WM

Protein painting reveals solvent-excluded drug targets hidden within native protein-protein interfaces.

• DOI: 10.1038/ncomms5413
• 发表时间: 2014-07-22
• 期刊: NATURE COMMUNICATIONS
• 影响因子: 16.6
• 作者: Luchini, Alessandra;Espina, Virginia;Liotta, Lance A.
• 通讯作者: Liotta, Lance A.

Cancer metabolism and mass spectrometry-based proteomics.

• DOI: 10.1016/j.canlet.2013.11.003
• 发表时间: 2015-01
• 期刊: Cancer letters
• 影响因子: 9.7
• 作者: Weidong Zhou;L. Liotta;E. Petricoin