Nanolytica 2016, held May 20 at the University of California at Berkeley, was organized by PerkinElmer (PE, Shelton, Conn.) and the Bay Area Nanotechnology Council of the IEEE (www.ieee.org). PE has an outstanding reputation for developing and marketing analytical instruments. IEEE promotes material science, particularly in solid-state electronics.
Nanolytics attempts to exploit changes in properties and experimental design that occur when sizes are reduced to the low-nanometer or single-molecule scale. For example, when there are two or more molecules of a drug–antibody conjugate, what can be surmised about the homologs containing different drug-to-antibody ratios? Is the sample a homogeneous or heterogeneous mixture? What is the distribution of drug occupancy at particular sites? How do changes in occupancy and adjacency affect safety and efficacy? In hetergeneous catalysis, is the active site of a nanometal cluster the surface, the edge or, perhaps, a corner? In one case, presented by Dr. Matteo Cargnello (Stanford University, Palo Alto, Calif.), the active site for oxidation is at the corner of the metal cluster. Chemists seek to improve catalytic activity by increasing access to corners in metal clusters.
Dr. Meyya Meyyappan (NASA’s Ames Research Center, Santa Clara, Calif.) described the use of carbon nanotubes (CNTs) as sensors for complex mixtures. CNTs have a specific surface area of 1600 m2/g and are thermally stable. Rates of adsorption of gases and vapors are very high, which provides rapid responses. CNTs can be doped with sorbents that change electrical capacitance, resistance and dielectric constant; when the sorbent captures target molecules, the dielectric constant changes, which then changes the capacitance of the solvent-nanotube structure. When assembled into a small array, the pattern of electrical changes provides qualitative and quantitative information. Typical arrays are 32 CNTs in a 4 × 8 configuration. So far, the arrays have been tuned to detect HCN, HCl, Cl2 NO and C6H6. Others have been used to characterize radioactive emissions.
Hydrophobic nanocoating reduces fouling and drag
Aquatic organisms attach to polar surfaces with very high tenacity: the resulting deposits can impede fluid flow, whether within a pipe or along a ship bottom. Since the attachment often requires specific strong bonds between the organism and the supporting surface, replacing a polar surface with a hydrophobic surface made of CNTs should reduce fouling. Resistance to liquid flow on a large scale, including pipeline transport, consumes about 1% of the global energy diet; thus, reduced surface fouling could be beneficial throughout industry.
Drug uptake
The efficacy of platinum-containing drugs used in chemotherapy is not uniform. About a third of patients receiving cis-platinum show little benefit; others have much better outcomes. Platinum drugs are attracted to bends in the DNA, where they disrupt transcription. Previously, drug distribution was measured over a population of cells, but the resulting overall average was not very useful. Dr. Lauren Amable (NIH, Bethesda, Md.) measured the uptake in single cells using ICP/MS. While this sounds easy, she encountered several challenges. Removing cells from the well wall is difficult and, once removed, the cells need to be dispersed. This was accomplished with a dilute solution of DNAse. The suspended cells were sensitive to freeze/thaw cycles. Software needed to be created to provide F/T history of individual samples. Cells settled while waiting for their turn in the sample queue. Amable found that the metal content of individual cells varies over a tenfold range.
Now that there is a tool (ICP/MS) that shows heterogeneity of uptake, the problem has shifted to how to use the data.
Quantum dots
Quantum dots are often made from CdSe. However, Cd+2 is toxic, which limits utility for imaging living organisms. Dr. Folarin Erogbogbo (California State University at San Jose) described work on making quantum dots from silicon. These fluoresce at specific wavelengths depending upon size, from blue to near-infrared (NIR).
Instruments for nanolytics
PerkinElmer has over a dozen instruments relevant to different aspects of nanoanalytics. Systems for measuring physical properties, particularly for mechanical properties and stability, include the TMA 4000 thermomechanical analyzer and DMA 8000. These are used in designing composites and for controlling production processes for solar cells. In proteomics, post-translational modification (PTM) of proteins adds “molecular foliage” such as methylation, glycosylation and polyethylene glycol, which are studied by LC/MS and UV/VIS/IR instruments like the Altus SQ LC/MS and Lambda 1050 UV/VIS/NIR spectrophotometer.
Nanoparticle composition can be measured with PE NexION 350 ICP/MS series instruments. The Titan MPS microwave sample preparation system is used in the analysis of viruses, dendrimers, quantum dots and liposomes. Rounding out the analytics for antibodies, proteins and nucleic acids, including aptamers, are the PE LS 55 fluorescence spectrometer and TG-IR GC/MS.
Dr. Cady Stephan (PerkinElmer, Waltham, Mass.) pointed out that nanomaterials are already appearing in a variety of products, including cell phones and cosmetics. On a larger scale, nanoparticles are used to impart beneficial properties to a variety of composites. Stephan described an ICP/MS that detects single nanoparticles (NPs) with parts-per-quadrillion (ppq) limits. The instrument uses ambient ion ionization to ablate material from a surface and ionize it for assay in a time-of-flight (TOF) mass analyzer.
Another interesting instrument was the TGA 4000, a thermogravimetic (TG) unit that fed an evolved gas to an infrared or mass spectrometer. Infrared spectroscopy provided the fingerprint of evolved pyrolysis gases, while MS delivered sensitive quantitation. Dr. Changseok Han (U.S. EPA, Cincinnati, Ohio) described the use of thermogravimetric analysis (TGA) to study adsorption of pollutants on nanoparticles. Upon heating, volatile analytes sorbed on the nanoparticles are released; thus, Dr. Han was able to study weathering of the composites.
Molecular Vista (San Jose, Calif.) presented a poster on the Vista IR system for nanochemical imaging. A noncontact atomic force microscope (AFM) serves as the base. Sample is irradiated with light from a tunable IR laser. As the AFM traverses the surface, a second laser is focused on the cantilever, delivering photo-induced force microscopy, which resolves sub-wavelength features. Applications include imaging molecular spectra of block copolymers and topography of physical micromixture polymers. Run times are a few minutes to a few tens of minutes, depending on the sample and application.
Commercial nanoanalytics
Several speakers focused on the evolving nanomaterials business. Dr. Kumar Virwani (IBM Almaden Research Center, San Jose, Calif.) reported the frustrating results to date on developing a lightweight lithium/air battery. Discharge is good, but recharging is difficult due to low solubility of the products.
Ms. Sarah Applebaum (Pangaea Ventures, Vancouver, B.C.) discussed the point of view of Canadian venture capital firms on material research and nanotechnology. They like to invest just prior to exit points, which generally occur when technical feasibility (~3 years after initial funding) is demonstrated or just prior to going to market (~10 years).
Dr. Ross Kozarsky of Lux Research Inc. (Boston, Mass.) focused on the life cycle of material technology and firms. Companies are looking for materials that are better and less expensive, and seek to invest in ventures demonstrating market pull, usually offered by partnerships already serving a significant market. According to Kozarsky, only 7–10% of startups are successful.
Nanolytica 2016 presented a balanced program where dreams were confronted with reality. Lectures described the chemistry supporting the dream, while reports of practical problems and low success rates were the reality.
Robert L. Stevenson, Ph.D., is Editor Emeritus, American Laboratory/Labcompare; e-mail: [email protected].