CAREER:"ASSURED" electrochemical platform for multiplexed detection of Cancer Biomarker Panel using Shear-Enhanced Nanoporous-Capacitive Electrodes

医疗点设备中使用的许多生物传感器存在选择性和灵敏度限制，限制了它们在检测和监测传染病(如艾滋病毒和某些癌症)方面的应用。为了缓解这些局限性，将开发一种新的高灵敏度和高选择性的电化学生物传感器。选择性和灵敏度的提高将通过在电极之间填充纳米结构来产生高剪切力来实现。预期的结果是一种生物传感器，可以在非常低的浓度下检测、识别和量化多个乳腺癌生物标记蛋白。相关科学开辟了令人兴奋的新途径，如用于检测水中阿片类药物的电化学测量，以及治疗药物新制造技术的开发。首席研究员将寻求研究、实验和教育的紧密结合。该中心将培养对生物传感技术领域感兴趣的下一代科学家和工程师，并指导本科生和研究生水平的研究人员(包括少数族裔和女性)，并通过动手演示启发K-12科学和工程领域的学生在其学习生涯的早期阶段。用于传染病或癌症早期诊断的生物传感器对于早期干预、患者护理和降低患者死亡率至关重要。目前的生物传感器通常在低浓度时失效，因为它们不够灵敏(防止假阴性)或选择性(防止假阳性)。该项目的总体目标是开发一种新的电化学传感方法，该方法使用剪切增强、流动、纳米孔和电容电极技术，从而产生非常灵敏和选择性的生物传感器。新型生物传感器的性能将超过现有生物传感器的性能，因为(I)电极的纳米孔度将促进氢键量级的剪切力的发展，通过减轻非特异性吸附，将显著提高选择性；(Ii)生物传感器的设计将消除寄生双电层电容等信号伪影，从而有助于快速、高分辨率地表征结合信号，显著降低噪声，从而提高灵敏度；以及(Iii)纳米多孔电极结构将增加感兴趣的分析物到传感元件的对流传输，从而克服扩散限制并减少分析时间。为了促进生物传感器的发展，PI将调查、分析和模拟生物传感器从单一物种的目标生物分子与其互补的生物传感元件结合的电化学响应。我们将详细研究纳米孔电容电极的物理化学特性与增强剪切力之间的关系。将开发一种多路电化学表征方法，以使用真实世界的复杂样本来测试乳腺癌生物标记物面板，并验证生物传感器技术与商业分析的对比。该项目的多学科性质将用于培训各级学生的实验室和实验技术，并增加他们选择跨学科研究作为职业道路的可能性。这项外展工作将利用社交媒体，利用我们现有的教育关系，包括课堂演示、教师培训和与NJIT荣誉学院的教育同行指导会议。这次STEM宣传活动的目标人群包括新泽西州纽瓦克和新泽西州尤尼翁等地的市中心高中，这些学校主要服务于代表人数较少的学生群体。还将为研究生开发统计培训讲习班和相关工具，以增加统计循证培训。经过验证的评估工具将被用来评估这些外展和教育活动的成功。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

Many biosensors used in point-of-care devices suffer from selectivity and sensitivity limitations that restrict their application in detecting and monitoring infectious diseases (such as HIV and certain cancers). To mitigate these limitations, a new electrochemical biosensor with high sensitivity and selectivity will be developed. The improvement in selectivity and sensitivity will be realized through packing nanostructures between electrodes to generate high shear forces. The expected outcome is a biosensor which detects, identifies and quantifies multiple breast cancer biomarker proteins at very low concentrations. The related science opens exciting new avenues such as electrochemical measurements for the detection of opioids in water and the development of new manufacturing techniques for therapeutic drugs. The principal investigator will seek close integration among research, experiments and education. The PI will train the next generation of scientists and engineers who are interested in the area of biosensing technology, and mentor researchers (including minorities and female) at undergraduate and graduate level, as well as inspire K-12 students in science and engineering fields at the early stage of their learning career through hands-on demonstrations. Biosensors for early diagnostics of infectious diseases or cancer are vitally important for early intervention, patient care, and reduction of patient mortality. Current biosensors often fail at low concentrations, as they are not sufficiently sensitive (to prevent false-negatives) nor selective (to prevent false-positives). The overall objective of this project is to develop a new electrochemical sensing method that uses a shear-enhanced, flow-through, nanoporous and capacitive electrode technology, resulting in a very sensitive and selective biosensor. The performance of new biosensor will exceed that of current biosensors as (i) the electrode nanoporosity will facilitate the development of shear forces of the order of a hydrogen bond that will significantly increase selectivity by mitigating non-specific adsorption; (ii) the design of the biosensor will negate signal artifacts such as the parasitic double layer capacitance, thus facilitating rapid, high-resolution characterization of the binding signal with a significant reduction in noise leading to increased sensitivity; and (iii) the nanoporous electrode architecture will increase convective transport of the analyte of interest to the sensing element, thus overcoming diffusion limitations and reducing assay times. To facilitate the development of the biosensor, the PI will investigate, analyze and model the electrochemical response of the biosensor from the binding of a single species of target biomolecule to its complementary biological sensing element. The effects of physiochemical characteristics of the nanoporous capacitive electrode along with the enhanced shear forces will be studied in detail. A multiplexed electrochemical characterization method will be developed to test for breast cancer biomarker panel using real-world, complex samples and to validate the biosensor technology against commercial assays. The multidisciplinary nature of this project will be used to train students at all levels in laboratory and experimental techniques, and increase the likelihood that they would choose interdisciplinary research as a career path. This outreach effort will harness social media, leverage our existing educational relationships, and include classroom demonstrations, teacher training, and educational peer-mentored conference with NJIT Honors College. Among the target populations of this STEM awareness campaign are inner-city high schools in the locales of Newark, NJ and Union, NJ that primarily serve largely underrepresented student bodies. Statistical training workshops and related tools will be also developed for graduate students to increase statistical evidence-based training. Validated assessment tools will be used to evaluate the success of these outreach and educational activities.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.