Nanobiotechnology: Nanoscience & Nanotechnology

Nanobiotechnology: MOLECULAR MANUFACTURING FOR THE GENOMIC AGE

hen it comes to understanding into his expanding nanobiotech world. SPEED AND RESOLUTION biology, Professor Carl A. Batt “A human hair is 100 000-nm wide, the There is a powerful rationale behind Batt’s W believes that size matters – average circuit on a Pentium chip is 180 claim that size is important to the under- especially at the Cornell University-based nm, and a DNA molecule is 2 nm, or two standing of biology. Nanoscale devices Nanobiotechnology Center that he co- billionths of a meter,”Batt told the audience. can acquire more information from a small directs. Founded in January 2000 by “We’re not yet at the point where we sample with greater speed and at better virtue of its designation as a Science and can efficiently and intelligently manipulate resolution than their larger counterparts. Technology Center and supported by the single molecules,” he continued, “but that’s Further, molecular interactions such as National Science Foundation, the center the goal. With advances in nanotechnology, those that induce disease, sustain life, and seeks to fuse advances in microchip tech- we can build wires that are just a few stimulate healing all occur on the nano- nology with the study of living systems. atoms wide. Eventually, practical circuits meter scale, making them resistant to study Batt, who is also professor of Food will be made up of series of individual via conventional biomedical techniques. Science at Cornell, recently presented an atoms strung together like beads and “Only devices built to interface on the Academy gathering – entitled “Nanotech- serving as switches and information stor- nanometer scale can hope to probe the nology: How Many Angels Can Dance on age devices.” mysteries of biology at this level of detail,” the Head of a Pin?” – with a tiny glimpse Batt said. “Given the present state of the

Nanoscience & Nanotechnology: BUILDING A BIG FUTURE FROM SMALL THINGS

anotechnology has gained wide- a revolutionary field. Rather, it is the para- assembly offers the potential to produce spread recognition with the prom- digm shift from top-down manufacturing, structures with enhanced and/or com- N ise of revolutionizing our future which has dominated most areas of tech- pletely new function. Unlike conventional through advances in areas ranging from nology, to a bottom-up approach. top-down fabrication, bottom-up assem- computing, information storage and The bottom-up paradigm can be bly makes it possible to combine materials communications to biotechnology and defined simply as one in which functional with distinct chemical composition, struc- medicine. How might one field of study devices and systems are assembled from ture, size and morphology virtually at will. produce such dramatic changes? well-defined nanoscale building blocks, To implement and exploit the potential At the most obvious level nanotechnol- much like the way nature uses proteins power of the bottom-up approach ogy is focused on the science and tech- and other macromolecules to construct requires that three key areas, which are nology of miniaturization, which is widely complex biological systems. The bottom- the focus of our ongoing program at recognized as the driving force for the up approach has the potential to go far Harvard University, be addressed (Figure). advances made in the microelectronics beyond the limits of top-down technology First and foremost, the bottom-up industry over the past 30 years. However, by defining key nanometer-scale metrics approach requires nanoscale building I believe that miniaturization is just one through synthesis and subsequent blocks with precisely controlled and small component of what makes and will assembly – not by lithography. tunable chemical composition, structure, make nanoscale science and technology Of equal importance, bottom-up morphology and size, since these charac-

4 Update October 2002 technology, there’s no limit to what we can build. The necessary fabrication skills are all there.” Scientists like Batt and his colleagues SIS/ artist name at Cornell and the center’s other academic partners are proceeding into areas previ- ously relegated to science fiction. While their work has a long way to go before there will be virus-sized devices capable of fighting disease and effecting repairs at the cellular level, progress is substantial. Tiny biodegradable sensors, already in development, will analyze pollution levels and measure environmental chemicals at multiple sample points over large dis- tances. Soon, we’ll be able to peer directly into the world of nano-phenomena and understand as never before how proteins fold, how hormones interact with their receptors, and how differences between single nucleotides account for distinctions between individuals and species. The trick – and the greatest challenge Continued on page 6

teristics determine their corresponding physical (e.g. electronic) properties. From the standpoint of miniaturization, much emphasis has been placed on the use of molecules zenges in establishing reliable electrical contact to molecules has limited the development of realistic schemes for scalable interconnection and integration without having key feature sizes being defined by the conventional lithography used to make interconnects. My own group’s work has been focused on the nanoscale wires and, in particular, nanosystems. nanoscale field-effect transistors, light- semiconductor nanowires as building Currently, semiconductor nanowires emitting diodes, bipolar junction transistors blocks. This focus was initially motivated can be rationally synthesized in single and complementary inverters – components by recognition that the one-dimensional crystal form with all key parameters – that potentially can be used to assemble a nanostructures represent the smallest including chemical composition, diameter wide range of powerful nanosystems. morphology structure for efficient routing and length, and doping/electronic proper- Tightly coupled to development of our of information — either in the form of ties – controlled. The control that we have nanowire building blocks have been stud- electrical or optical signals. Subsequently, over these nanowire properties has corre- ies of their fundamental properties. Such we have shown that nanowires can also spondingly enabled a wide range of measurements are critical for defining exhibit a variety of critical device function, devices and integration strategies to be their limits as existing or completely and thus can be exploited as both the pursued. For example, semiconductor new types of device elements. We have wiring and device elements in functional nanowires have been assembled into Continued on page 6

October 2002 Update 5 Continued from page 5 patible. Batt names proteins, nucleic acids the traditional integrated circuit industry. posed by an emerging field that is melding and other polymers as the appropriate But for industry outsiders, the traditional the physical and life sciences in unprece- building blocks of the new devices, which technology is already complex enough. dented ways – is to adapt the “dry,” silicon- will rely on chemistries that bridge the Anna Waldron, the Nanobiotechnology based technology of the integrated circuit organic and inorganic worlds. Center’s Director of Education, routinely to the “wet” environment of the living cell. In silicon-based fabrication, some conducts classes and workshops for materials that are common in biological schoolchildren, undergraduates and grad- BRIDGING THE ORGANIC – systems – sodium, for example – are con- uates to initiate them into the world of INORGANIC DIVIDE taminants. That’s why nanobiotech fabri- nanotechnology, encourage them to pur- Nanobiotechnology’s first order of busi- cation must take place in unique facilities sue careers in science, and foster science ness is to go beyond inorganic materials designed to accommodate a level of and technology literacy. and construct devices that are biocom- chemical complexity not encountered in In a hands-on presentation originally designed for elementary-school children, Waldron gives the audience a taste – both literally Figure Caption. Building the and figuratively – of photolithog- future is as easy as 1-2-3. Key raphy, a patterning technique stages of the bottom-up paradigm that is the workhorse of the are illustrated for nanowires: (1) semiconductor industry. Instead The synthesis of well-defined of creating a network of wells nanowire building blocks and and channels out of silicon, how- elucidation of novel properties/ ever, Waldron works her magic device concepts, such as a on a graham cracker, a choco- crossed nanowire field-effect transistor, which have the poten- tial for massive integration by assembly. (2) Scalable assembly of nanowires into parallel and more complex arrays from fluid solutions, where sequential steps ful and scalable approach for can be used to combine different assembly on multiple length scales. materials. (3) Implementation of In this method, sequential ‘layers’ nanowire arrays as functional of different nanowires can be systems for nanoscale computing deposited in parallel, crossed and and multicolor light sources. more complex architectures to build up functional systems (2, Figure). In addition, the readily Continued from page 5 lead to greatly improved device charac- accessible crossed nanowire matrix developed a new strategy for nanoscale teristics such as high gain, high speed and represents an ideal configuration since transistors, for example, in which one low power dissipation. Moreover, this new the critical device dimension is defined by nanowire serves as the conducting chan- approach has enabled highly integrated the nanoscale cross point, and the nel and the other crossed nanowire as the nanocircuits to be defined by assembly. crossed configuration is a naturally a gate electrode (1, Figure). Significantly, Second and central to the bottom-up scalable architecture that can enable the three critical device metrics are natu- concept has been the development of massive system integration. rally defined at the nanometer scale in hierarchical assembly methods that can Third, combining the advances in assembled crossed nanowire transistors: organize building blocks into integrated nanowire building block synthesis, under- (1) a nanoscale channel width determined structures. To obtain highly integrated NWs standing of fundamental device properties by the diameter of the active nanowire; circuits require techniques to align and and development of well-defined assem- (2) a nanoscale channel length defined by assemble them into regular arrays with bly strategies has allowed us to move well the crossed gate nanowire diameter; and controlled orientation and spatial location. beyond the limit of single devices and (3) a nanoscale gate dielectric thickness We have shown that fluidics, in which begin to tackle the challenging and determined by the nanowire surface solutions of nanowires directed in chan- exciting world of integrated nanosystems. oxide. These distinct nanoscale metrics nels over a substrate surface, is a power- Significantly, high-yield assembly of

6 Update October 2002 late bar and a marshmallow, manufactur- tion reservoir of genomics into vital insights made devices which can correct genetic ing a mouthwatering “nanosmore” chip in that illuminate the relationship between mutations by cutting and pasting DNA at a matter of minutes. structure and function,” he said. the 2-nanometer scale. One of the great- Graham crackers are substituted for Also down the road, ATP-fueled molec- est obstacles to their development, Batt silicon substrate, while chocolate provides ular motors may drive a whole series of said, doesn’t lie in building the devices, the necessary primer for the surface. ultrasmall, robotic medical devices. A but in powering them. Once the right ener- Marshmallows act as the photoresist, an “lab-on-a-chip” will test new drugs, and a gy sources are identified and channeled, organic polymer that, when exposed to “smart pharmacist” will roam the body to we’ll have a technology that speaks the light, radiation, or, in this case, a heat gun, detect abnormal chemical signals, calcu- language of genomics and proteomics, can be patterned in the desired manner. late drug dosage and dispense medication and decodes that language into narratives Finally, a Teflon “mask” is placed on top of to molecular targets. we can understand. –Carl A. Batt the marshmallow layer and a blast from Thus far, however, there are no man- the heat gun transfers the mask’s design to the marshmallow’s surface – a result that appeared to leave a lasting impres- sion on the Academy audience as well. Microbiologist Carl A. Batt is Professor of Food WHAT’S NEXT? Science at Cornell University and Co-Director of According to Batt, it won’t be too long the Nanobiotechnology Center, an NSF-supported before the impact of the nanobiotech rev- Science and Technology Center. He also runs a lab- olution will be felt in the fields of diagnos- oratory that works in partnership with the Ludwig tics and biomedical research. “Progress in Institute for Cancer Research. these areas will translate the vast informa-

crossed nanowire structures containing addressable memory element with a poten- spectrum can be directly assembled from multiple active cross points has led to the tial for integration at the 1012/cm2 level. emissive electron doped binary and terna- bottom-up organization of OR, AND, and In a completely different area, we have ry semiconductor nanowires crossed with NOR logic gates, where the key integration shown that nanowires can serve as nearly nonemissive hole doped silicon nanowires did not depend on lithography (3, Figure). universal electrically based detectors of (3, Figure). These nanoscale light-emitting Moreover, we have shown that these chemical and biological species with the diodes can excite emissive molecules for nanologic gates can be interconnected potential to impact research in biology, sensing or might be used as single photon to form circuits and, thereby, carry out medical diagnostics and chem/biowarfare sources in quantum communications. primitive computation. detection. Lastly, and to further highlight The bottom line – focusing on the diverse These and related advances have this potential, we have shown that science at the nanoscale will provide the created tremendous excitement in the nanoscale light-emitting diode arrays with basis for enabling truly unique technolo- nanotechnology field. But I believe it is colors spanning the ultraviolet to near- gies in the future. –Charles M. Lieber the truly unique characteristics of the infrared region of the electromagnetic bottom-up paradigm, such as enabling completely different function through rational substitution of nanowire building Dr. Charles M. Lieber moved to Harvard University in 1991 as a blocks in a common assembly scheme, Professor of Chemistry and now holds a joint appointment in which ultimately could have the biggest the Department of Chemistry and Chemical Biology, where he impact in the future. The use of modified holds the Mark Hyman Chair of Chemistry, and the Division of nanowire surfaces in a crossed nanowire Engineering and Applied Sciences. He is the principal inven- architecture, for example, has recently led tor on more than 15 patents and recently founded a nanotech- to the creation of nanoscale nonvolatile random access memory, where each nology company, NanoSys, Inc. cross point functions as an independently

October 2002 Update 7