Nanobiotechnology, Biosensors & Bioinspired Devices
(Cady Group)

Scope: The Cady group focuses on the unique interface between nanotechnology and biology. Research in our group falls into the following two general categories:

Approaching nanotechnology from the biological world -
Nanoscale innovations and technologies from the biological world are harnessed to manipulate and control materials at the nanoscale. Drawing knowledge from biological systems enables unique approaches to nanotechnological design, engineering, processing and manufacturing.

Approaching biology from the nanoscale -
Nanoscale phenomena, technologies or processes are used to study biology at its fundamental level – the nanoscale. Similarly, nanoscale devices, materials, or phenomena can be harnessed for therapeutics, diagnostics, medicine, pharmaceuticals, and many other biological applications.

Goals: Develop cutting-edge nanotechnologies for biological research and employ biological principles for developing novel nano-devices.

TOPIC 1: Antifouling and Biofilm Remediation
Microbial fouling of surfaces and subsequent formation of biofilms is a major problem in medicine, industrial processes, and infrastructure. To combat fouling and biofilm formation, we are pursuing methods to limit bacterial attachment to surfaces and interrupt biofilm formation (or disrupt established biofilms). We are currently developing 3D nanomanufacturing strategies to create nanoscale topographical features that can be used to limit the attachment of bacterial cells to stationary surfaces (Figure 1). Our work has shown that topography in the 0.5 – 1 micrometer size scale is effective in reducing bacterial adhesion to surfaces, and that larger scale topography can increase surface attachment (as compared to flat reference surfaces). We are also exploring the combined use of topography and surface chemistry to further limit cell attachment and subsequent biofilm formation. These experiments are performed in novel microfluidic flow systems that allow us to observe surfaces microscopically during the experiment. This “real-time” view of the experimental system allows us to have a unique understanding of the various phases of biofouling, including initial surface attachment, surface motility/rearrangement, growth, and propagation/biofilm formation.

Figure 1: Topographically patterned surfaces used for antifouling experiments in the Cady group (NanoLIFE, 2012).

We are also working with collaborators (including Prof. Rabi Musah, UAlbany – Dept. of Chemistry and Prof. Alexander Rickard, UMichigan-School of Public Health) to develop molecular antagonists of biofilm formation and methods of delivering these antagonists for prophylactic or therapeutic treatment against biofilms. Our initial work in this area has focused on the inhibition of bacterial biofilm formation by a library of natural products inspired compounds. Prof. Musah’s group has developed these compounds, which we have shown to have efficacy against Pseudomonas aeruginosa biofilm formation. Interestingly, we also showed that these compounds are effective in reducing cell signaling (quorum sensing) behavior of P. aeruginosa. Our hypothesis is that disruption of quorum sensing pathways in P. aeruginosa affects the expression of genes involved in biofilm formation. While we are continuing to investigate this system, we are also pursuing this approach for organisms involved in oral biofilm formation. To this end, Dr. Musah’s group is synthesizing a new library of compounds with structures that mimic quorum sensing signal molecules found in many Gram positive oral biofilm formers (eg. Streptococcus mutans, Streptococcus sanguinis, Actinomyces oralis). Our goal is to isolate compounds that reduce biofilm formation in these organisms and then develop strategies to use them prophylactically, or integrate them into dental devices for cavity prevention.

Figure 2: Confocal micrographs of P. aeruginosa biofilms inhibited by natural products inspired compounds (PLoS One, 2012).

Related Recent Publications:
N.C. Cady, J. Behnke, R. Kubec, K. McKean, and R.A. Musah. Inhibition of Biofilm Formation, Quorum Sensing and Infection in Pseudomonas aeruginosa by Natural Products-Inspired Organosulfur Compounds. (2012) PLoS One. 7(6): e38492.

J.F. Ling, M.V. Graham, N.C. Cady. Topographically patterned poly(dimethylsiloxane) surfaces affect Pseudomonas aeruginosa adhesion and biofilm formation. (2012) Nano LIFE. 2(4): 1242004.

A.P. Mosier, A.E. Kaloyeros, N.C. Cady. Determination of Bacterial Biofilm Elastic Properties using Microfluidic-Assisted AFM Analysis. Accepted for publication in “Journal of Microbiological Methods” July 2012. In press.

TOPIC 2: Cell Patterning/Tissue Engineering
To better understand how cells behave in complex microenvironments, the Cady group has pursued novel patterning strategies to attach cells to surfaces in fixed geometric patterns, which has resulted in a novel direct cell printing technology. This cell printing technology grew out of a collaboration with the company BioForce Nanosciences, that developed a nanoscale printing instrument called the Nano eNabler. My group beta-tested this instrument and developed our own microscale “quill pen” printing components for live, whole-cell printing. This approach to live cell printing is much different than technique such as ink-jet or laser-based cell printing, both of which impart high thermal and shear forces on cells during the printing process. We have currently been using our cell printing methods to study innate cell signaling (eg. bacterial quorum sensing), as well as metabolic cross-feeding in synthetic or evolved bacterial systems (with our collaborator, Prof. Christopher Marx at Harvard University – Dept. of Organismic & Evolutionary Biology). We also use “quill pen” printing for various tissue engineering related projects. This has resulted in successful printing of mouse embryonic stem cells (mESCs), as shown in Figure 3. We have expanded our surface patterning efforts to a collaboration with Prof. Michelle Lennartz (Albany Medical College) and are also pursuing tissue engineering related work with Prof. Melinda Larsen (University at Albany).

Figure 3: Confocal micrograph of quill-pen patterned mouse embryonic stem cells in Extracel matrix (hyaluronic acid, gelatin, crosslinker).

Related Recent Publications:
S.J. Sequeira, D.A. Soscia, B. Oztan, A.P. Mosier, R. Jean-Gilles, A. Gadre, N.C. Cady, B. Yener, J. Castracane, M. Larsen. The regulation of focal adhesion complex formation and salivary gland epithelial cell organization by nanofibrous PLGA scaffolds. (2012) Biomaterials. 33: 3175-3186.

S.J. Sequeira, D. Soscia, B. Oztan, A. Mosier, R. Jean-Gilles, A. Gadre, N. Cady, B. Yener, J. Castracane, M. Larsen. Nanofiber scaffolds regulate focal adhesion complex formation and salivary gland epithelial cell organization. (2012) Biomaterials. 33: 3175-3186.

N.C. Cady, J.L. Behnke, A.D. Strickland. Copper-based nanostructured coatings on natural cellulose: Nanocomposites exhibiting rapid and efficient inhibition of a multi-drug resistant wound pathogen, A. baumannii, and mammalian cell biocompatibility in vitro. (2011) Advanced Functional Materials. 21(13): 2506-2514.

D.A. Soscia, N.A. Raof, Y. Xie, N.C. Cady, A.P. Gadre. Antibiotic-loaded PLGA nanofibers for wound healing applications. (2010) Advanced Engineering Materials: Special Issue “Advanced Biomaterials”. 12(4): B83-B88.

TOPIC 3: Biosensor Development
We are currently focusing on field effect transistors (FETs) for sensitive detection and analysis of DNA hybridization and/or DNA damage events. A major focus of this work is to develop unique DNA immobilization strategies that optimize device sensitivity while also retaining native DNA structure and function. This includes the study of DNA interactions on materials used in modern nanoscale electronics, including high-K dielectrics, metal oxides, and compound semiconductors, as well as fabrication and testing of FET-based DNA sensors. This work is performed in collaboration with semiconductor physicists and engineers at the College of Nanoscale Science & Engineering, including Prof. Serge Oktyabrsky and Prof. Shadi Shahedipour-Sandvik. These collaborators focus on device engineering, while my group focuses on the interactions of biomolecules with device materials. We have developed unique strategies for linking DNA to semiconductor materials, including direct, coordination based linkage of phosphate-terminated molecules with metal oxides and Group III-nitride materials (Figure 4).

Figure 4: DNA attachment to hafnium oxide surfaces via terminal phosphate linkage. (ACS Applied Materials and Interfaces, 2012)

In addition to work on FET-based biosensors, our group is also focused on integrated biosensing platforms. Integrated platforms include components for sample preparation and target detection. Through a collaboration with Dr. David Lawrence (Wadsworth Institute), we are developing a sensor platform that incorporates a microfluidic blood fractionation device with a grating coupled surface plasmon resonance sensor. This work is supported by a National Cancer Institute grant for development of new technologies for evaluating circulating tumor cells.

Figure 5: Microfluidic blood fractionation chip.

Related Recent Publications:
N.M. Fahrenkopf, P.Z. Rice, M. Bergkvist, N.A. Deskins, N.C. Cady. Immobilization mechanisms of deoxyribonucleic acid (DNA) to hafnium dioxide (HfO2) surfaces for biosensing applications. (2012) ACS Applied Materials Interfaces. 4(10): 5360–5368.

N.M. Fahrenkopf, F. Shahedipour-Sandvik, N. Tokranova, M. Bergkvist, N.C. Cady. Direct attachment of DNA to semiconductor materials for biosensor applications. (2010) Journal of Biotechnology. 150(3): 312-314.

N.C. Cady, S. J. Stelick, and C. A. Batt. PCR-based detection of Bacillus anthracis using an integrated microfluidic platform. (2011) International Journal of Biomedical Nanoscience & Nanotechnology. 211(2): 152-166.

C. Lui, S.J. Stelick, N.C. Cady and C.A. Batt. Low-Power Microfluidic Electro-hydraulic Pump (EHP). (2010) Lab on a Chip. 10: 74-79.

TOPIC 4: Resistive Memory Devices (Memristors)
The Cady group has worked closely with the Center for Semiconductor Research (CSR) during 2012 on the projects titled above to produce resistive memory devices (RMDs, aka: memristors). These devices behave similar to neural synapses, as their “memory state” depends on the current and voltage history of the device. This is a good example of bioinspired/biomimetic research, since the biological process of synapse formation is being mimicked by a physical device. The goal of our Air Force Research Laboratory supported research program is to develop RMDs that can be integrated into reprogrammable, low-power encryption systems. RMDs have a metal-insulator-metal structure and controllably change between resistance states by applying voltage/current. Two oxide materials have been investigated to produce back-end-of-line (BEOL) compatible RMDs: HfOx and CuxO. Devices fabricated form these oxides have shown promising results. HfOx-based RMDs exhibited consistent on- and off-voltages from 10 µm to 48 nm, as shown in the figure below (left). To avoid the interfacial voiding that occurs in copper oxidation, the Cady group has invented a novel oxygen implantation process to synthesize copper oxide. We have demonstrated RMDs fabricated from implantation-synthesized copper, titanium and tantalum oxides.

Figure 6: (a) Typical bipolar switching behavior from an implantation-synthesized tantalum oxide RMD. (b) Graph showing the SET and RESET voltage in TaOx RMDs as a function of the SET current.

Related Recent Publications:
S.M. Bishop, B.D. Briggs, P.Z. Rice, J.O. Capulong, H. Bakhru, N.C. Cady. Ion implantation synthesis and conduction of tantalum oxide resistive memory layers. (2012) Journal of Vacuum Science & Technology B. 31(1): 012203.

P.Z. Rice, B.D. Briggs, S.M. Bishop, N.C. Cady. Development of a silicon oxide based resistive memory device using a spin-on hydrogen silsesquioxane precursor. (2012) Journal of Materials Research. Online Publication - DOI: 10.1557/jmr.2012.390

S.M. Bishop, H. Bakhru, J.O. Capulong, N.C. Cady. Influence of the SET current on the resistive switching properties of tantalum oxide created by oxygen implantation. (2012) Applied Physics Letters. 100, 142111.

N.R. McDonald, S.M. Bishop, B.D. Briggs, J.E. Van Nostrand, N.C. Cady. Influence of the plasma oxidation power on the switching properties of Al/CuxO/Cu memristive devices. (2012) Solid-State Electronics. Online publication:

S.M. Bishop, H. Bakhru, S.W. Novak, B.D. Briggs, R.J. Matyi, and N.C. Cady. Ion Implantation Synthesized Copper Oxide-based Resistive Memory Devices. (2011) Applied Physics Letters. 99, 202102.