For the last 60 years, the steady rise of Moore's law has created the electronic computer chip, and with it the computer and smartphone revolutions. In the last 20 years it has become clear that integrating biological molecules and a variety of functional nanoparticles with computer chips will create new revolutions. From DNA and proteins to carbon nanotubes to semiconductor quantum dots, molecular and particulate nanodevices exhibit performance and properties which are hard to achieve with conventional silicon microfabrication. They will be the basis of new biochips that read DNA sequences and detect proteins, as well as new types of quantum computers.

Unfortunately, most such devices must be synthesized or processed in solution. To get molecular and particulate nanodevices out of solution and onto chips where we can connect them to electronics, and control them or read out the information they generate, is a very difficult challenge.  DNA origami shapes, which are themselves giant 100-nanometer molecules, have provided a way to solve this problem. When used as a carrier for a nanodevice, DNA origami shapes act as an adaptor, bridging the nano-world of the device and the micro-world of the chip. We use the techniques of semiconductor microfabrication to print binding sites for the DNA origami on the surface of a chip, so that they can be attracted to the chip and form a well-ordered grid.  This means that any devices they carry are similarly arranged neatly into a grid.

This project solved two remaining problems for how to use DNA origami to integrate nanodevices with chips. First, asymmetric DNA origami shapes were devised, analyzed theoretically, and synthesized to show that they could be used to control the orientation of nanodevices on surfaces. Without control of orientation, many devices might land upside down, or at the wrong angle relative to other devices on the chip surface. We demonstrated this principle by landing fluorescent molecules in a pattern that reveals the polarization of incident light. This process is very expensive so we devised a second, low-tech process that could be done in a home kitchen. It enables grids of devices to be created at a much lower cost, although it does not allow the orientation of the devices to be controlled. It is suitable for many applications in biology, such as DNA sequencing, where the orientation of a single molecule is often irrelevant.

Despite the success of DNA origami as adaptors for manipulating novel nanodevices on chips, there remain some problems with their use. They are expensive to make chemically and they do not interface well with living biological systems.  To solve these challenges, we turned to RNA origami, which can be biologically synthesized very inexpensively, via bacteria, and which natural interfaces with a variety of proteins, enabling them to serve as scaffolds for enzymatic factories. RNA origami, as a field, is much less mature than DNA origami, and they are difficult to design and synthesize.  Thus, a third major outcome of this award was a validated software package that allows large RNA origami to be designed. To demonstrate the utility of the software package, we synthesized dozens of RNA origami, of record-breaking size, and used a number of them as scaffolds, to define the spacing between proteins and small molecules that bind them.

Taken together, the results of this award make a dramatic impact on the scalable nanomanufacturing of DNA and RNA based nanodevices.

Last Modified: 05/10/2021
Modified by: Paul W.K. Rothemund