Nanoliter Lab-on-a-Chip for Blood Diagnostics

描述(申请人提供)：使用大型仪器进行诊断需要大量的血液(毫升)，在极低出生体重的早产儿中，内源性失血或“出血进入实验室”是实施小容量输血的重要原因。研究发现，用于诊断的抽血量和随后的输血量之间存在直接的相关性。对于新生儿，可能没有收集到足够的血液样本来进行所有必要的测试。此外，在现场(事故、灾难、战场等)对血液样本进行常规实验室分析。是不切实际的。 一种手持、自动化、廉价、多分析和多路复用的血液化学分析仪将有助于将血液分析量从毫升减少到纳升，减少进一步输血的需要，并使分析仪可在护理地点(诊所、手术室和急诊室、重症监护病房和现场)使用。基于我们之前演示的从芯片储存库分配的纳米升大小的试剂和样品的电润湿操作、高速传输、混合、分解和稀释以及分析的比色检测，将开发一种一次性芯片实验室。最终，将开发一种用于血液化学的一次性芯片实验室，其中1微升的人类血液将作为手持系统的输入，并以完全自动化的方式输出血液化学。 第一阶段的工作将侧重于制造一个微流控平台，在该平台上，将从微升大小的来源液滴中分配纳米升的血清液滴、参考标准液滴和试剂液滴，以二维方式运输、混合、检测和处置。将开发专门针对微流控系统的分析方法。人体血清中四种重要和常见的分析物(血尿素氮、肌酐、葡萄糖和乳酸)的比色分析将被证明为建立纳升芯片实验室用于血液化学的可行性。

DESCRIPTION (provided by applicant): Large volumes of blood (milliliters) are required for diagnostics with large instruments, latrogenic blood loss or "bleeding into the laboratory" is an important reason for administration of small volume transfusions in very low birth weight, premature infants. A direct correlation was found between the volume of blood drawn for diagnostics and subsequent volume transfused. In neonatal infants, there may not be enough collected blood sample to perform all the necessary tests. Also, conventional laboratory analysis of blood samples while in the field (accidents, disasters, battlefield, etc.) is impractical. A handheld, automated, inexpensive, multi-analyte and multiplexed blood chemistry analyzer will help reduce the blood analysis volume from milliliters to nanoliters, reduce the need for further transfusions, and make the analyzer available at the point-of-care (clinics, operating and emergency rooms, intensive care units, and in the field). Based on our previous demonstrations of electrowetting manipulation of nanoliter-sized droplets of reagents and sample for dispensing from on-chip reservoirs, high-speed transport, mixing, splitting and dilution, and colorimetric detection of the assays, a disposable lab-on-a-chip will be developed. Ultimately, a disposable lab-on-a-chip for blood chemistry will be developed where 1 microliter of human blood will be the input to the handheld system and it outputs the blood chemistry in a completely automated fashion. Phase I work will focus on fabricating a microfluidic platform upon which nanoliters of blood serum droplets, reference standards, and reagent droplets will be dispensed from microliter-sized source drops, transported in 2 dimensions, mixed, assayed, and disposed. Assays specific to the microfluidic regime will be developed. Colorimetric assays of four important and common analytes (blood urea nitrogen, creatinine, glucose, and lactate) in human blood serum will be demonstrated establishing just feasibility of a nanoliter lab-on-a-chip for blood chemistry.