BioForce Nanosciences Holdings, Inc.

BioForce Nanosciences, Inc. (BFNH.OB) develops and commercializes nanotechnology tools and applications for the life sciences. The company is based in Ames, Iowa, and has two divisions – instruments and applications. The instrument division includes the Nano eNabler™ system and associated consumables (SPT™ print cartridges and Sindex™ substrates) and a surface decontamination device known as the ProCleaner™. The applications division develops Nano eNabler-based applications for a variety of purposes. The current application pipeline includes the patented ViriChip™ pathogen detection and identification system, the Chip-On-A-Tip™ ultraminiaturized cancer biomarker detection system and a proprietary method for high-throughput molecular interaction screening known as FAST™. The unique capabilities of the Nano eNabler system allow the creation of novel applications that take advantage of vastly reduced spatial scales and sample volumes. Popular applications of the Nano eNabler system include: functionalizing biosensors, including micro-electromechanical systems/nano-electromechanical systems devices; patterning surfaces with molecules to study cell growth, behavior and differentiation; performing ultrasensitive bioassays; and printing arrays in confined spaces in microfluidic devices.

Novel quill-type cantilever-based surface patterning tools (SPTs) were designed and constructed for use in controlled placement of femtoliter volumes of biological molecules on surfaces for biological applications. These tools were fabricated from silicon dioxide using microelectromechanical systems (MEMS) techniques. They featured a 1 microm split gap, fluidic transport microchannels and self-replenishing reservoirs. Experimental trials were performed using these tools on NanoArrayer molecular deposition instrumentation. Cy3-streptavidin was loaded as a biological sample and patterned on an amine-reactive dithiobis-succinimidyl undecanoate (DSU) monolayer on gold. Results showed these tools were capable of generating high quality biological arrays with routine spot sizes of 2-3 microm. The spot size could potentially achieve sub-micron dimensions if these SPT designs are reduced in size by more precise microfabrication techniques. The geometric designs of these tools facilitated sample replenishment from the local reservoir on the cantilever which allowed printing of large numbers of spots without sample reloading.

Antibody adsorption to solid surfaces creates a number of constraints that may interfere with epitope recognition and ligand-antibody interaction. By optimizing the conditions of adsorption, one may minimize these constraints. We have studied several factors that affect the antibody adsorption using atomic force microscopy (AFM) as a readout mechanism. AFM provides a highly sensitive, label-free method for detecting and analyzing molecular interactions. In this report, AFM was used to study antibody properties, the efficiency of particle capture and ligand-antibody interaction using anti-bacteriophage fd antibodies in a solid phase assay format. The capture efficiencies of anti-fd preparations adsorbed onto gold surfaces under various conditions including pH and antibody concentration were determined and compared. The relative sensitivities of each antibody for the capture of phage fd as a function of applied phage concentrations was evaluated. The collective data indicates that AFM is effective as an analytical instrument for studying the functionality of surface adsorbed antibodies in particle capture assays. This method of analysis can be extended to rapidly screen and select antibodies or other ligands with a specific set of characteristics. As the number and complexity of chip-based analytical platforms in proteomics increases, rapid selection/screening processes such as that described here will become invaluable.