This Small Business Innovation Research Phase I project aims to develop a commercial optically resonant nanotweezer chip. The nanotweezer technology, originally developed at Cornell University, uses photonic resonance to localize optical forces so they can be used to directly manipulate biological (nucleic acids & proteins) and non-biological (nanoparticles) materials as small as a few nanometers in size. It has recently been used to demonstrate the manipulation of the smallest dielectric matter ever, as well as individual strands of DNA. We will focus our efforts on developing a commercial system which facilitates the study of the single molecule interactions, as this has the most immediate market appeal. At present, research into the understanding of how single molecules interact is greatly impeded by the lack of a simple technique which can: (1) capture and suspend small molecules in free solution for an indefinite period of time (2) effectively "concentrate" the set of molecules of interest to a point where protein-protein or other multi-molecule interactions can be studied and (3) allow rapid modulation of the external environmental conditions. The nanotweezer system to be developed here has the potential to solve all three of these problems simultaneously.
The broader impact/commercial potential of this project is that it will result in a commercially available product that can directly manipulate extremely small particles and molecules, and could be transformative to scientific and industrial advancement in a number of areas including: (1) the analysis of individual nucleic acids for rapid sequencing and direct haplotyping, (2) the directed assembly of new forms of nanomaterials for energy production, and (3) the understanding of faulty protein-protein events and other single molecule interactions. The importance of the latter of these (which is the target application for the initial version of this chip) is highlighted by the large number of diseases that have been linked to such events, in particular neurodegenerative disorders such as Alzheimer's, Parkinson's and Huntington's. The development of tools that can facilitate experimental studies of how single biomolecules and small aggregates interact can reveal information about the fundamental molecular processes that lead to these deficiencies. The nanotweezer technology has a series of key advantages over existing commercial technologies that can enable researchers to better understand these phenomena in environments closer to the physiological state. We believe that these advantages will give us a significant commercial advantage over competing products.
The objective of this Small Business Innovation Research project was to develop a technology that will allow researchers in molecular biology to directly manipulate (move, trap and release) very small biological entities like proteins, and DNA so that their fundamental mechanical and biological behavior can be studied. The core technology that makes this type of manipulation possible is called photonics, which is a means to manipulate the way light is guided on a chip much like a computer chip guides electricity. Briefly, our proprietary technology works much like the tractor beams from the Starship Enterprise(r) in Star Trek(r), but it is designed to capture small biological molecules in liquids as opposed to enemy ships in space. That is why we call this technology the Molecular NanoTweezer. Our technology walks around the fundamental physical limitations that other competing technologies like traditional optical tweezers simply cannot overcome. With the unique ability to manipulate biological matter such a small scale, we believe our instrument offers molecular biologists the unique capability of performing their experiments and analysis of proteins without interruption and for extended periods of time by keeping their proteins or targets of interest in a precise (trapped) place where they can be studied. The technology is not only designed to help enable new experiments, but to automate their traditionally tedious experiments which rely on sluggish surface chemistry techniques. Our envisioned system, consists of an instrument and a chip consumables which host the core of the technology. This business model allows us to scale production due to the mass producibility of the semiconductor materials used for chips. The major outcomes of this project for this SBIR Phase I were: 1)Designed a robust packaging of the Molecular NanoTweezer chip. It was important to design a robust and shippable chip, and this SBIR allowed us to take the initial technology which was developed at Cornell University, and turned it into a microscope add-on that can be easily incorporated into a traditional molecular biologist's workflow. For this we built a microscope adapter, made the fluidic packaging more robust and worked on a simple way to introduce light on our chips in a way that does not require a highly trained biophysicist. 2): Demonstrate an array of capabilities of the Molecular NanoTweezer chip: We were able to use our chips to manipulate biological and nonbiological matter from 200nm to 10 nm in size (from the size of large viruses down to small proteins) suspened in liquid solutions and pushed our design to function with a type of laser light that ensures that almost no heat is imparted on to the molecules by the trapping process. 3) Began instrument design and fabrication: Most of the work was done on the heart of the technology which is the chips, as it was proposed. However, we also designed and began building the instrument that will deliver the laser light (again used for trapping) and the reagents (proteinsor other biological matter suspended in solution) to the chips. To ensure that traditional molecular biologists will adopt our instrument, we also began building a software package to make the system as easy to use and automated as possible. With these 3 key technical accomplishments achieved in Phase I of this effort, we will primarily use the funds in Phase II for device development and to bring us one step closer to commercialization.
