Chip-based nLC-TOF-MS is a highly stable technology for large-scale high-throughput analyses

Many studies focused on the discovery of novel biomarkers for the diagnosis and treatment of disease states are facilitated by mass spectrometry-based technology. HPLC coupled to mass spectrometry is widely used; miniaturization of this technique using nano-liquid chromatography (LC)-mass spectrometry (MS) usually results in better sensitivity, but is associated with limited repeatability. The recent introduction of chip-based technology has significantly improved the stability of nano-LC-MS, but no substantial studies to verify this have been performed. To evaluate the temporal repeatability of chip-based nano-LC-MS analyses, N-glycans released from a serum sample were repeatedly analyzed using nLC-PGC-chip-TOF-MS on three non-consecutive days. With an average inter-day coefficient of variation of 4 %, determined on log₁₀-transformed integrals, the repeatability of the system is very high. Overall, chip-based nano-LC-MS appears to be a highly stable technology, which is suitable for the profiling of large numbers of clinical samples for biomarker discovery.     

Experimental study of copper leveling additives and their wafer and pattern-scale effect on copper planarization

The impact of Cu leveling additives on electrodeposited Cu topography and subsequent planarization behaviour was studied on both the pattern and wafer scales. The leveling agent significantly reduces as-deposited Cu topography, especially “mounding”. The reduction in topography results in a higher effective Cu removal rate during subsequent Cu planarization, both at the pattern and wafer scales. On the wafer scale, this effect is more evident for lower overburdens as the topography must be eliminated in a shorter total polish time. For Cu electrodeposited from leveler additive-free chemistries, significant pattern-scale topography persists throughout almost the entire planarization process, whereas for Cu deposited using a leveling agent only very wide features (～ > 100 μm) show any significant topography evolution during Cu polish. It is shown that excess electrodeposited Cu topography can lead to poor in-plane Cu wiring leakage performance.     

Analysis of Overlapped and Noisy Hydrogen/Deuterium Exchange Mass Spectra

Noisy and overlapped mass spectrometry data hinder the sequence coverage that can be obtained from hydrogen deuterium exchange analysis, and places a limit on the complexity of the samples that can be studied by this technique. Advances in instrumentation have addressed these limits, but as the complexity of the biological samples under investigation increases, these problems are re-encountered. Here we describe the use of binomial distribution fitting with asymmetric linear squares regression for calculating the accurate deuterium content for mass envelopes of low signal or that contain significant overlap. The approach is demonstrated with a test data set of HIV Env gp140 wherein inclusion of the new analysis regime resulted in obtaining exchange data for 42 additional peptides, improving the sequence coverage by 11 %. At the same time, the precision of deuterium uptake measurements was improved for nearly every peptide examined. The improved processing algorithms also provide an efficient method for deconvolution of bimodal mass envelopes and EX1 kinetic signatures. All these functions and visualization tools have been implemented in the new version of the freely available software, HX-Express v2.

The Use of tert-Butyl Vinyl Ether in Stepwise Electrophilic Addition Reactions

tert-Butyl vinyl ether (1) reacts with p-TolSCl to give 2-tert-butoxy-2-chloroethyl p-tolyl sulfide (2). In the presence of SnCl₄, 2 reacts with silyl enol ethers, allyltrimethylsilane, and vinyl ethers to form a C-C bond. In the case of vinyl ethers, the reaction proceeds through the formation of the 5-membered sulfonium salt intermediate which in turn can react with H₂O, TMSCN, allyltrimethylsilane, and Grignard reagents.     

Polarizing-alignment layers for twisted nematic cells

We describe polarizing films formed from the lyotropic liquid crystalline phases of dyes dissolved in water. The dye polarizers possess a high dichroic ratio close to that of conventional polarizers. In addition, the dried dye films provide a uniform homogeneous orientation for thermotropic nematic materials. Therefore, thin dye films can simultaneously serve as internal polarizers and as alignment agents. These properties make them especially suitable for twisted nematic devices based on low cost birefringent plastic substrates.     

Tetrakis(imidazolyl)borate-based coordination polymers: group II network solids,M[B(Im)4]2(H2O)2 (M = Mg,Ca, Sr)

We are using the coordinating anion tetrakis(imidazolyl)borate to construct new metal-organic framework structures. In this report, we present three alkaline earth metal network solids incorporating this anion. All three compounds have the same formula, M[B(Im)(4)](2)(H(2)O)(2) (M = Mg, Ca, Sr), and the same coordination environment about the metal. However, the three compounds have different network structures with different degrees of hydrogen bonding; the Mg material forms a two-dimensional network and the Ca and Sr compounds form one-dimensional chains. In addition, we present the structure of the protonated anion B(HIm)(Im)(3) as a model for the default structure of this anion and discuss how the conformation of tetrakis(imidazolyl)borate can affect the structure of network solids.     

Electrically actuated, pressure-driven microfluidic pumps

In order to make the lab-on-a-chip concept a reality, it is desirable to have an integrated component capable of pumping fluids through microchannels. We have developed novel, electrically actuated micropumps and have integrated them with microfluidic systems. These devices utilize the build-up of electrolysis gases to achieve pressure-driven pumping, only require small voltages (approximately 10 V), and have approximate dimensions of 5 cm x 3 cm x 2 cm. Furthermore, these micropumps are composed of relatively inexpensive materials, and the reversible sealability of their poly(dimethylsiloxane) body to different microfluidic arrays enables repeated uses of the same pump. Under an applied potential of 10 V, three different micropumps had average flow rates of 8-13 microL min(-1) for water being pumped through five different 2 cm-long, 5500 microm(2) cross-sectional-area channels in poly(methyl methacrylate), in approximate agreement with predicted pump rates. We have also evaluated pump operation at the lower applied potential of 8 V and observed an average flow rate of 6.1 microL min(-1) for a pump-channel system. The current micropump design is capable of sustaining pumping pressures in the range of 300 kPa. The various advantages of these micropumps make them well suited for use in lab-on-a-chip analysis techniques.     

Amphiphilic Heterografted Molecular Bottlebrushes with Tertiary Amine-Containing Side Chains as Efficient and Robust pH-Responsive Emulsifiers

By combining the unique characteristics of molecular bottlebrushes (MBBs) and the properties of stimuli-responsive polymers, we show that MBBs with randomly grafted poly(n-butyl acrylate) and pH-responsive poly(2-(N,N-diethylamino)ethyl methacrylate) (PDEAEMA) side chains are efficient and robust pH-responsive emulsifiers. Water-in-toluene emulsions were formed at pH 4.0 and disrupted by increasing the pH to 10.0. The emulsion generation and disruption was reversible over the ten cycles investigated, and the bottlebrushes remained intact. The exceptional emulsion stability stemmed from the high interfacial binding energy of MBBs, imparted by their large molecular size and Janus architecture at the interface, as evidenced by the interfacial jamming and wrinkling of the assemblies upon reducing the interfacial area. At pH 10.0, PDEAEMA became water-insoluble, and the MBBs desorbed from the interface, causing de-emulsification. Consequently, we have shown that the judicious design of MBBs can generate properties of particle emulsifiers from their large size, while the responsiveness of the MBBs enables more potential applications.     

Progress in the quality assurance of environmental trace organic analysis

An overview is given on the stepwise learning programmes undertaken to identify the main sources of error associated with the determination of the mandatory organic contaminants in the marine monitoring programmes. Details are given on the preparation and use of LRMs and CRMs to maintain analytical control and quantify the laboratory errors in relation to the measurement of changes in the environment.