CONSPECTUS: Nucleic acids have become powerful building blocks for creating supramolecular nanostructures with a variety of new and interesting behaviors. The predictable and guided folding of DNA, inspired by nature, allows designs to manipulate molecular-scale processes unlike any other material system. Thus, DNA can be co-opted for engineered and purposeful ends. This Account details a small portion of what can be engineered using DNA within the context of computer architectures and systems. Over a decade of work at the intersection of DNA nanotechnology and computer system design has shown several key elements and properties of how to harness the massive parallelism created by DNA self-assembly. This work is presented, naturally, from the bottom-up beginning with early work on strand sequence design for deterministic, finite DNA nanostructure synthesis. The key features of DNA nanostructures are explored, including how the use of small DNA motifs assembled in a hierarchical manner enables full-addressability of the final nanostructure, an important property for building dense and complicated systems. A full computer system also requires devices that are compatible with DNA self-assembly and cooperate at a higher level as circuits patterned over many, many replicated units. Described here is some work in this area investigating nanowire and nanoparticle devices, as well as chromophore-based circuits called resonance energy transfer (RET) logic. The former is an example of a new way to bring traditional silicon transistor technology to the nanoscale, which is increasingly problematic with current fabrication methods. RET logic, on the other hand, introduces a framework for optical computing at the molecular level. This Account also highlights several architectural system studies that demonstrate that even with low-level devices that are inferior to their silicon counterparts and a substrate that harbors abundant defects, self-assembled systems can still outperform conventional systems. Further, the domain, that is, the physical environment, in which such self-assembled computers can operate transcends the usual limitations of silicon machines and opens up new and exciting horizons for their application. This Account also includes a look at simulation tools developed to streamline the design process at the strand, device, circuit, and architectural levels. These tools are essential for understanding how to best manipulate the devices into systems that explore the fundamentally new computing domains enabled by DNA nanotechnology.
Using a microarray platform for allergy diagnosis allows for testing of specific IgE sensitivity to a multitude of allergens, while requiring only small volumes of serum. However, variation of probe immobilization on microarrays hinders the ability to make quantitative, assertive, and statistically relevant conclusions necessary in immunodiagnostics. To address this problem, we have developed a calibrated, inexpensive, multiplexed, and rapid protein microarray method that directly correlates surface probe density to captured labeled secondary antibody in clinical samples. We have identified three major technological advantages of our calibrated fluorescence enhancement (CaFE) technique: (i) a significant increase in fluorescence emission over a broad range of fluorophores on a layered substrate optimized specifically for fluorescence; (ii) a method to perform label-free quantification of the probes in each spot while maintaining fluorescence enhancement for a particular fluorophore; and (iii) a calibrated, quantitative technique that combines fluorescence and label-free modalities to accurately measure probe density and bound target for a variety of antibody–antigen pairs. In this paper, we establish the effectiveness of the CaFE method by presenting the strong linear dependence of the amount of bound protein to the resulting fluorescence signal of secondary antibody for IgG, β-lactoglobulin, and allergen-specific IgEs to Ara h 1 (peanut major allergen) and Phl p 1 (timothy grass major allergen) in human serum.
wileyonlinelibrary.comvariety of mechanisms such as DNA strand displacement, [ 3,[6][7][8] excited singlet saturation, [ 9,10 ] and optochemically accessed dark states of standard chromophores. [11][12][13][14][15][16][17] To store state in these networks, researchers have developed RET based fl ip-fl ops [ 16 ] and write-once polychromatic RET based storage devices with densities 1000 times greater than current standards. [ 18 ] Tying all of these circuit elements together is an impressive array of RET wires that can transport excitons through geometrically complex DNA nanostructures spanning more than 20 nm in length. [19][20][21][22][23][24] Given these extensive contributions, it is clear that the foundations for building more complex RET circuits have already been established.Despite these advances in essential circuit elements, the intrinsic energy loss of these networks currently prohibits large scale circuit fabrication. Energy loss is defi ned as the red-shifting Stokes effect that excitons incur as they traverse a set of RET donor-acceptor pairs. Once in the excited state, vibrational relaxation forces each fl uorophore's emission spectrum to be red-shifted with respect to its excitation spectrum. This shift requires an acceptor's excitation spectrum be lower in energy than its donor. Accordingly, as an exciton traverses any RET network from input to output it loses energy. Without a way to restore this energy, the output of one network cannot act as the input to a subsequent network, thereby prohibiting the cascading of independently designed RET networks to form larger circuitry. In certain cases, it may be possible to design an entire set of cascaded logic operations as a single RET network ensuring that the design does not violate this downhill energy fl ow; however, such solutions cannot be scaled to fabricate arbitrarily large circuits. Instead, we have engineered a device that will restore the energy of the excitons as they transition from one network to the next. This concept is analogous to a buffer in digital logic that decouples two networks and restores the signal between them. To achieve this restoration, we explored the use of upconversion.Upconverting processes combine many low energy inputs to form high energy outputs. The most commonly utilized upconversion processes rely entirely on far-fi eld interactions, e.g., multiphoton excitation of fl uorophores or excited state absorption in upconverting laser media. Such far-fi eld mechanisms, however, are unfi t for restoring energy in RET Networks of fl uorophores arranged at the nanoscale can perform basic computation using resonance energy transfer (RET) to transport and manipulate information in the form of excitons. As excitons travel through RET circuits, they are red-shifted due to vibrational energy loss at each transfer event. This loss prohibits RET circuits from being cascaded to form larger, more computationally complex systems. To address this issue, a nanoassembly capable of converting three or more low energy excitons into a si...
We demonstrate an optically controlled molecular-scale pass gate that uses the photoinduced dark states of fluorescent molecules to modulate the flow of excitons. The device consists of four fluorophores spatially arranged on a self-assembled DNA nanostructure. Together, they form a resonance energy transfer (RET) network resembling a standard transistor with a source, channel, drain, and gate. When the gate fluorophore is directly excited, the device is toggled on. Excitons flow freely from the source to the drain, producing strong output fluorescence. Without this excitation, exciton flow through the device is hindered by absorbing paths along the way, resulting in weak output fluorescence. In this Letter, we describe the design and fabrication of the pass gate. We perform a steady-state analysis revealing that the on/off fluorescence ratio for this particular implementation is ∼8.7. To demonstrate dynamic modulation of the pass gate, we toggle the gate excitation on and off and measure the corresponding change in output fluorescence. We characterize the rise and fall times of these transitions, showing that they are faster and/or more easily achieved than other methods of RET network modulation. The pass gate is the first dynamic RET-based logic gate exclusively modulated by dark states and serves as a proof-of-concept device for building more complex RET systems in the future.
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