One of the most tangible benefits of scientific research to society is in the field of medicine where novel therapies and diagnostics have extended and improved the lives of billions of individuals. The key to the success of many of these diagnostic methods for past 40 years has been the monoclonal antibody which lies at the heart of clinical analytical methods, has an important emerging role in therapeutics, and is a vital research tool.

While tremendously important, antibodies have a number of limitations including high cost, thermal instability, and the requirement that they be generated from cells and animals. In contrast, aptamers are single stranded nucleic acids ligands which offer many advantageous features, including lower cost, thermal stability, and the ability to be chemically synthesized, making them a potential alternative to antibodies. However, two major challenges have impeded their broader use in commercial applications. Specifically, the aptamer generation process requires substantial time and resources, and selections often fail to yield molecules with affinities suitable for high performance diagnostics and therapeutics.

Towards both understanding and overcoming these challenges we developed a microfluidic selection process that can be used to obtain high affinity aptamers against diverse protein targets. We also show that affinity can be further enhanced through directed evolution of a DNA scaffold to position multivalent aptamers with atomic level precision. The ultimate goal is the rapid generation of affinity reagents against the entire proteome on demand.

But the best performing assays are useless if their cost and complexity curtail their widespread deployment. The best way of solving the unmet diagnostic needs of the next century and beyond will be to leverage existing proven technologies with newer ones which lower the barriers to their widespread use. To that end, we demonstrate that a commodity desktop computer can function as a thermal cycler for PCR with no hardware modifications (PC-PCR). With PC-PCR amplification we can detect pathogenic DNA from whole blood samples without any sample processing and perform rapid post-PCR analysis using an ordinary mobile phone camera. By using a common desktop computer and mobile phone camera, and by avoiding tedious sample preparation, we can accelerate the sample-to-answer process and facilitate the shift of molecular diagnostics out of centralized facilities and closer to the individuals that rely on its results.