Portable DNA-Probe-Array Synthesis System Using Acoustic-Wave Ejector and Atomizer Array

为了有效和方便地进行DNA测序，我们建议开发一种便携式的按需DNA探针阵列合成系统，使用二维MEMS喷射器阵列(以任何所需的顺序将DNA碱基射出到DNA探针芯片上)和原子化器阵列(将未结合的DNA碱基从探针芯片上分散开)。所提出的系统的技术创新如下：(1)喷射器阵列(不同于喷嘴式喷射器)可以以任何角度喷射液滴，并且不必移动来墨迹带有四个DNA碱基的斑点；(2)原子化器阵列(在一个斑点步骤之后)雾化未结合的DNA碱基，并在转移到另一个斑点步骤用于DNA合成之前吹掉不需要的碱基，从而省去了昂贵的洗涤和干燥步骤。此外，我们将在单个硅芯片上集成2-D喷射器阵列与微通道、腔和其他微流体处理部件，以实现一个小型、便携、负担得起的系统。便携式DNA探针合成系统将允许遗传学家在其站点的芯片上产生任何DNA序列的任意二维阵列。主要研究目标之一是开发一种灵活、低成本的技术，用于高效的基因分型，以表征数百个DNA样本的特定突变，用于分子遗传学或分子流行病学研究。基因分型目前非常耗时(因此非常昂贵)，现在正是开发一种高效和灵活的基因分型技术的时候，这种技术可以根据需要在玻璃芯片上形成任何DNA序列。拟议的活动还将包括(1)让来自代表性不足群体的学生参与研究(通过积极搜索此类申请者并对选定的学生进行更多的指导)；(2)通过互联网网站传播数据和信息，该网站通过喷墨打印DNA碱基或多肽在芯片表面合成DNA和蛋白质微探针阵列的详细信息；以及(3)与南加州大学医学院的一个研究小组密切合作，该研究小组专门从事用于基因分型和公共卫生问题表型分析的DNA测序。

For efficient and convenient DNA sequencing, we propose to develop a portable system for on-demand DNA probe-array synthesis, using two-dimensional MEMS ejector array (to shoot out DNA bases onto a DNA probe chip in any desired sequence) and atomizer array (to scatter away unbound DNA bases from the probe chip). The technical innovations of the proposed system are as follows: (1) the ejector array (unlike a nozzle-based ejector) can eject liquid droplets at any oblique angle, and does not have to be moved to ink a spot with four DNA bases, and (2) the atomizer array atomizes the unbound DNA bases (after a spotting step), and blows off the unwanted bases before moving to another spotting step for DNA synthesis, thus removing the costly step of the washing and drying steps. Also, we will integrate the 2-D ejector array with microchannels, chambers and other microfluidic handling components on a single silicon chip for a small, portable, affordable system. The portable DNA probe synthesis system will allow geneticists to produce any two dimensional array of any DNA sequence on a chip at their sites.One major research objective is to develop a flexible, low cost technology for an efficient genotyping to characterize hundreds of DNA samples for specific mutations for molecular genetic or molecular epidemiologic research. Genotyping is currently very time-consuming (and, therefore, very expensive), and it is timely to develop an efficient and flexible genotyping technique that allows formation of any DNA sequences on a glass chip on demand. The proposed activity will also include (1) research involvement of students from underrepresented groups (through active search of such applicants and more than usual mentoring of the selected students), (2) data and information dissemination through an internet web site that describes detailed information on DNA and protein microprobe-array synthesis on a chip surface through ink-jet printing of DNA bases or peptides, and (3) close collaboration with a research group (at USC's medical school) that specializes on DNA sequencing for genotyping and phenotyping for public health concerns.