Abstract
Laboratory Automation and High-Throughput Chemistry
High-Throughput Screening and Evolution of a Library of Ligands in Asymmetric H-Transfer Reduction of Acetophenone
A library of 117 ligands is combined by C. de Bellefon et al. with three transition metals Ru, Rh, and Ir, and screened with three different operating conditions for the asymmetric H-transfer reduction of acetophenone into phenylethanol. The combinatorial approach is based on the evolution of a first library containing 60 ligands. For the evolution, operators, such as replication, regression, crossover, and mutation, are used. The study is performed with an XYZ robot and fast chiral GC analysis. Over only four generations, the average targeted criterion, enantioselectivity, increased from 20% to ca. 80% for the fourth generation. The best results provide enantiomeric excess up to 93% (Comb. Chem. High Throughput Screen.
Solution-Phase Parallel Synthesis of Substituted 3-Phenylsulfonyl[l,2,3]triazolo [l,5-a]quinazolines: Selective Serotonin 5-HT6 Receptor Antagonists
O. D. Mitkin et al. report the solution-phase parallel synthesis of a combinatorial library consisting of 776 new substituted 3-phenylsulfonyl-[l,2,3]triazolo [l,5-a]quinazolines and a study of the relationship of their structure with a 5-HT6 receptor antagonistic activity in functional cell analysis and radioligand competitive binding. The authors find highly active and selective 5-HT6R antagonists. The most active 5-HT6R antagonists have inhibitory concentration < 100 nM in a functional assay, and Ki <10 nM in a binding assay, which is 100 times higher than the activity with respect to other serotonin receptors (J. Comb. Chem.
Automated Maskless Photolithography System for Peptide Microarray Synthesis on a Chip
Maskless photolithographic peptide synthesis is performed by Y. S. Lee et al. on a glass chip using an automated peptide array synthesizer system. The peptide array synthesizer is built in a closed box, which contains optical and fluidic systems. The conditions for peptide synthesis are fully controlled by a computer program. For the peptide synthesis on a glass chip, protected amino acids are synthesized. The coupling efficiencies of two model peptide sequences are examined. The results demonstrate that the photolithographic peptide array synthesis method efficiently quantifies the binding activities of protein— peptide interactions, and it can be used for additional biological assay applications (J. Comb. Chem.
Privileged Scaffolds for Library Design and Drug Discovery
B. R. Stockwell et al. describe the concept of using privileged scaffolds to identify biologically active compounds by building chemical libraries. The authors aim to accomplish three main objectives: to provide one of the most comprehensive listings of privileged scaffolds; to reveal through four selected examples the present state of the art in privileged scaffold library synthesis; and to offer some thoughts on how new privileged scaffolds might be identified and exploited (Curr. Opin. Chem. Biol.
Current Strategies for Diversity-Oriented Synthesis
Compounds accessed through diversity-oriented synthesis (DOS) are showing promise in modulating the activities of several targets that are currently considered undruggable. Recently, many new DOS pathways have been developed using multicomponent reactions (MCRs), cycloadditions, ring-closing metathesis, and tandem processes. Functional group pairing and build/couple/pair strategies have been described as a means for generating structural diversity. Efforts have also been directed toward developing DOS libraries based on privileged scaffolds. S. Dandapani and L. A. Marcaurelle describe how recent studies provide several compelling examples for the utility of DOS compounds for producing novel biological probes, and application of DOS in the context of drug discovery is extremely appealing (Curr. Opin. Chem. Biol.
Recent Advances in Multicomponent Reactions for Diversity-Oriented Synthesis
Interest in
Selecting Chemicals: The Emerging Utility of DNA-Encoded Libraries
Over the past 10 years, several academic and industrial research groups have developed strategies for the synthesis and interrogation of DNA-encoded small-molecule libraries. These strategies can be divided into those in which DNA directs small-molecule synthesis and those in which it records the synthesis. M.A. Clark reviews how these libraries have started to yield novel modulators of biological targets, including SH3-domain-binding peptoids; macrocyclic peptide-based Bcl-XL/BH3 interaction disruptors; ligands for tumor necrosis factor, albumin, streptavidin, and others; and small-molecule kinase inhibitors (Curr. Opin. Chem. Biol.
Microfluidic Chip Technology and Micro Reactor Technology
Development and Application of a Solution-Phase Automated Synthesizer, ChemKonzert
One of the trends in synthetic organic chemistry has been to use automated synthesizers for high-speed synthesis of libraries to meet the requirements for bioassay studies. In their article, K. Machida et al. from the Development Department of ChemGenesis Incorporated (Tokyo Institute of Technology, Tokyo, Japan) describe the development of a fully automated solution-phase synthesizer, ChemKonzert, which can be used to prepare a wide variety of organic compounds. (Chem. Pharm. Bull.
ChemKonzert is designed on a unit concept, which means that the instrument is divided by functions—in particular, two reaction units, two solvent units, two reagent units, and a workup unit. Each unit and all the glassware are connected by Teflon tubes, which make up the flow-line system, and can be rinsed with water or acetone. Subsequently, lines can be dried by a vacuum pump and kept in an inert atmosphere. The footprint is decisively influenced by the use of rotary valves, stated to be only 1550(W) × 540(D) × 730(W) mm.
With this setup, the authors carry out typical solution-phase reactions used in the pharmaceutical and chemical industries, including (1) two-phase reaction to demonstrate the mixing ability, (2) temperature controlled reaction at reflux and 0 °C, (3) handling of air- and moisture-sensitive reagents, (4) handling precipitates after reaction is completed, and (5) a continuous two-step reaction. The construction and function of the units, the software, and the flowcharts for the different implemented syntheses are described in detail.
A Novel Multi-Channel Reactor System Combined with Operando UV/Vis Diffuse Reflectance Spectroscopy: Proof of Principle
High-throughput experimentation (HTE) for the development and optimization of heterogeneous catalysts is still a challenging field, particularly in combination with simultaneous catalyst characterization. M. J. G. Fait et al. from Leibniz Institute for Catalysis at Rostock University (Rostock, Germany) have introduced a 36-channel reactor system combining HTE with operando ultraviolet/visible (UV/vis) diffuse reflectance (UV/vis-DR) spectroscopy and applied it for the oxidative dehydrogenation of propane to propene (Catalysis Today
Besides testing the reliability of the analytical data and performance of the implemented catalysts, a detailed characterization of the VO2, V2O3, and V2O5 during the catalytic reaction is realized, and profound results are discussed. As a result, the catalyst working behavior studied under reaction conditions is in strong accordance with literature data, and vanadium species in different oxidation states along the catalyst bed can be identified unambiguously. In addition, the reactor can be used for the monitoring of coke formation and to trace certain calcinations or reduction procedures.
High-Throughput Analytics
Emerging Analytical Separation Techniques with High-Throughput Potential for Pharmaceutical Analysis, Part I: Stationary Phase and Instrumental Developments in LC
In recent years, increasing the sample throughput of the ever-growing number of necessary (routine) analyses has become a popular way for the pharmaceutical industry to save precious time. For the last 30 years, HPLC has been the leading analytical technology in the pharmaceutical industry; however, because serial analyses typically requires 10-45 min, it can become a sample throughput-limiting barrier. Lately, the fundamentals of HPLC have been exploited to raise new technologies that can speed up analyses to groundbreaking limits without compromising separation efficiency. Y. V. Heyden et al. review some promising technologies, that is, totally porous sub-2-μm particles accompanied by pressures up to 1000 bar (ultra-performance liquid chro-matography), fused-core particle technology, monolithic supports, and high-temperature liquid chromatography (Comb. Chem. High Throughput Screen.
Emerging Analytical Separation Techniques with High-Throughput Potential for Pharmaceutical Analysis, Part II: Novel Chromatographic Modes
In a second review article by Y. V. Heyden et al., the high-throughput potential of some novel chromatographic modes is surveyed. The modes are hydrophilic-interaction liquid chromatography, supercritical fluid chromatography, and polar organic solvent chromatography. Their high-throughput potentials are discussed in three domains, that is, drug discovery, bioanalysis in clinical drug development, and quality control (QC) testing, and is illustrated with some examples (Comb. Chem. High Throughput Screen.
Rapid Identification of Stabilizers in Polypropylene Using Time-of-Flight Mass Spectrometry and DART as Ion Source
Polyolefins are distinguished by outstanding material properties, such as chemical resistance, electrical insulating properties, and their favorable cost-performance ratio, and are one of the most important groups of synthetic materials. They can, however, be degraded by oxidation, which decreases the mechanical stability and changes the material color (yellowing). To prevent this degradation, stabilizers are added during the compounding process. Stabilizers are compounds with large variety, and in many cases, the exact mode of action is not completely determined. In most instances, a mixture (blend) of more than one stabilizer is used to protect the polymer. The material quality and the performance of a final product made of polyolefins are dependent on the stabilizer type and its concentration. Therefore, suitable analysis methods for stabilizer additives in bulk synthetic materials and in the final product are a fundamental requirement. Haunschmidt et al. present a fast method for identification of stabilizers in polypropylene using time-of-flight MS and direct analysis in real time (Analyst
The method does not require any previous sample pre-treatment and is distinguished by short analysis times. In the first step of this study, for a test set of 21 commonly used stabilizers, standard solutions and extracts prepared by a procedure for HPLC analysis are determined. In the subsequent step, commercial solid polymer samples containing stabilizers and, finally, decomposition products from polymer stabilizers are analyzed. The method presented enables a fast qualitative and quantitative analyses of up to 21 stabilizers in polymer samples in the form of extracts and solid materials without sample pretreatment. The detection of additive degradation during polymer compounding and supplemental processing is possible.
Automated Mass Spectrometric Analysis of Urinary and Plasma Serotonin
The neurotransmitter serotonin is involved in central nervous system neurotransmission processes and is a crucial hormone in a number of physiological processes outside the brain. Liver cell regeneration, valvular heart disease, bone formation, and psychiatric diseases are characterized by a depletion of serotonin. In contrast, extensive serotonin production has been noted in carcinoid tumors. It was found that platelet and urinary serotonins are the most accurate markers for the diagnosis of carcinoids. De Jong et al. developed an automated online solid-phase extraction (SPE)-liquid chromatographic method with tandem mass spectrometric detection for sample pretreatment and analysis of serotonin (Anal. Bioanal. Chem.
The sample cleanup is performed by online SPE using weak ion-exchange cartridges. The analyte serotonin is directly eluted on the analytical column. Subsequent samples are handled in parallel, and the cartridges are regenerated. The tandem mass spectrometer enables more specific detection than regularly used conventional HPLC methods. The selection of the precursor to product-mass transition is used for the identification of the analyte. The method presented is distinguished by easy handling, portability, and reduction of cost per sample. This is achieved by reduced sample preparation time (total runtime of 6 min), high-throughput operating, and reuse of the cartridges. Serotonin concentrations are analyzed in platelet-poor plasma and urine samples of metastatic patients and healthy controls. De Jong et al. provide an automated sample preparation and analytical method for serotonin determination with high sensitivity and specificity. This method can be applied for precise quantification of serotonin levels in platelet-poor plasma and urine samples in the field of routine diagnostics. Furthermore, the method enables investigations of the role of serotonin in serotonin-related disorders.
Fingerprinting of Yogurt Products by Laser Desorption Spray Post-Ionization Mass Spectrometry
Lactic acid beverages have a large market share in dairy products, especially in China. These are made by adding water and sugar and flavoring using milk powder or fermented milk. Some manufacturers try to imitate the flavor of yogurt. Such products are distinguished by a lower amount of lactic acid and a lower price. Adulterated and counterfeit yogurt may result in adverse consequences to health. Furthermore, these products are detrimental to businesses. The development of easy-to-use, rapid, and reliable analytical techniques is very important for product authentication and QC of yogurt and related products. Liu et al. present a laser desorption spray post-ionization MS (LDSPI-MS)-based method for fast, simple, and reproducible classification and detection of counterfeit yogurt without sample pretreatment (Rapid Commun. Mass Spectrom.
A commercial ion-trap mass spectrometer is extended by an external infrared (IR) laser and a home-made versatile spray-ion source. Immediately after the deposition on a gold surface, the yogurt samples are irradiated by the
To mathematically test the capability of
Bioautomation and Screening
Application of Chemistry-Based Functional Proteomics to Screening for Novel Drug Targets
Pharmaceutical companies are being forced by market competition to find new ways of novel drug target screening. The completion of human genome sequencing has provided a flood of new information that might help identify potential drug targets. Finding promising novel drug targets from this flood of information remains challenging. For de novo drug target screening, the interactions between a drug and cellular components must be comprehensively characterized for better understanding of the pharmacological activities of the drug. Multidisciplinary chemistry-based functional proteomics can be used to elucidate the interactions, because it provides a method to focus initial new drug target identification toward proteins that are more easily validated and most likely to be effective, thereby creating a higher potential for success. A review by C. Huang et al. covers major chemistry-based functional proteomic approaches and highlights their recent advances in applications for novel drug target screening (Comb. Chem. High Throughput Screen.
High-Throughput Cherry Picking of Solvated Samples
Advances in the design of automated compound storage systems have made it possible to store large collections of research compounds in individual single-use aliquots dissolved in dimethyl sulfoxide and rapidly retrieve a specific group of them. This cherry-picking approach offers researchers the opportunity to request large numbers of compounds desired for testing without also having to retrieve all the other compounds stored on the same rack or plate. This makes it possible to meet the increasing demand for samples from HTS and therapeutic area teams without adding staff to dispense powder each time without the constraints imposed by storage in solvated compounds in fixed-well 96- or 384-way plates, and without sacrificing sample quality or shelf life by storing at room temperature. R. Schmitt et al. describe how this approach is implemented at Abbott Laboratories’ central compound repository to provide smaller amounts of more compounds faster and with high quality (Comb. Chem. High Throughput Screen.
High-Throughput Screening Methodologies Classified for Major Drug Target Classes According to Target Signaling Pathways
When HTS technologies are categorized according to drug target class, assay formats can be subdivided into early-hit-stage assays (usually ligand-binding based) that are often straightforward and robust up to analysis of final cellular effects exerted by ligands. The latter provide not only higher content data but also better represent anticipated effects in the body. These assay formats are often elaborate, nonro-bust, and very time consuming to conduct, but become pivotal when going from the hit-to-lead discovery stage.
Looking at the hit-to-lead process, new assay possibilities in terms of measured effects and readout principles are continuously reaching the screening arena. Furthermore, at the early lead discovery stage, other targets also have to be evaluated to study, for example, target selectivity and
Enhancements of Screening Collections to Address Areas of Unmet Medical Need: An Industry Perspective
The past 20 years have witnessed an impressive expansion of the drug space defined as the intersection of the medicinal chemistry space and the biologically active space relevant in the quest for new treatments for disease. Despite the success of known lead discovery tactics, areas of unmet medical need are often linked to challenging or novel targets and are poorly served by current screening collections. David H. Drewry and Ricardo Macarron describe that a successful strategy to fill the gaps is to diversify the approaches taken in the enhancement of screening collections. Possible strategies include investments through proven methods, exploring areas of chemical space previously neglected (e.g., hydrophilic compounds, natural product mimics) and applying tactics to the lead discovery process that are complementary to HTS (e.g., fragment-based screening or multidisciplinary team efforts to tackle new target classes) (Curr. Opin. Chem. Biol.
Expanding the Range of “Druggable” Targets with Natural Product-Based Libraries: An Academic Perspective
Existing drugs address a relatively narrow range of biological targets. As a result, libraries of drug-like molecules have proven ineffective against a variety of challenging targets, such as protein-protein interactions, nucleic acid complexes, and antibacterial modalities. In contrast, natural products are known to be effective at modulating such targets, and new libraries are being developed based on underrepresented scaffolds and regions of chemical space associated with natural products. D. S. Tan et al. describe how this has led to several recent successes in identifying new chemical probes that address these challenging targets (Curr. Opin. Chem. Biol.
Apparent Activity in High-Throughput Screening: Origins of Compound-Dependent Assay Interference
Expansive compound collections made up of structurally heterogeneous chemicals, the activities of which are largely undefined, present challenging problems for HTS. Foremost is differentiating whether the activity for a given compound in an assay is directed against the targeted biology or whether the result of surreptitious compound activity involves the assay detection system. Such compound interference can be especially difficult to identify if it is reproducible and concentration dependent-characteristics generally attributed to compounds with genuine activity. Although reactive chemical groups on compounds were once thought to be the primary source of compound interference in assays used in HTS, recent work suggests that other factors, such as compound aggregation, may play a more significant role in many assay formats. J. Inglese et al. describe progress that has been made in profile-representative compound libraries in an effort to identify chemical classes susceptible to producing compound interference, such as compounds commonly found to inhibit the reporter enzyme firefly luciferase. Such work also has led to the development of practices that have the potential to significantly reduce compound interference, for example, through the addition of nonionic detergent to assay buffer to reduce aggregation-based inhibition (Curr. Opin. Chem. Biol.
Cheminformatic Approaches to Analyze Diversity in Compound Screening Libraries
Cheminformatics is playing an increasingly important role in selecting new compounds for diverse screening libraries. New visualization techniques, such as multifusion similarity maps, scaffold trees, and principal moments-of-inertia plots, provide complementary information on compound libraries and enable the identification of unexplored regions of chemical space with potential biological relevance. Quantitative metrics have been developed to analyze libraries for properties, such as natural product likeness and shape complexity. Analysis of HTS results and drug discovery programs identify compounds problematic for screening. L. B. Akella and D. DeCaprio claim that these approaches can be used to increase the diversity of biological outcomes available in compound screening libraries and to improve the success rates of HTS against new targets without making significant increases in the size of compound libraries (Curr. Opin. Chem. Biol.
Diversity-Oriented Fluorescence Library Approaches for Probe Discovery and Development
Diversity-oriented fluorescence library approaches have significantly accelerated the development of new sensors. By making use of combinatorial chemistry and HTS, they can circumvent limitations in designing probes for particular recognition processes. Combinatorial chemists have proved how to derivatize fluorogenic scaffolds, tune their photophysical spectra, and adjust their properties (from cell permeability to quantum yields) to generate libraries of potential sensors. Several platforms (in vitro assays, cell-based imaging) also have been optimized to screen these libraries in a high-throughput manner, and with recent progress in image acquisition and analysis, their scope has been expanded toward more diverse and demanding biological systems. Supported by successful examples of fluorescent sensors for bio-molecules, proteins, or even phenotypes, Y. T. Chang et al. review the important role that diversity-oriented approaches will continue to play in probe development (Curr. Opin. Chem. Biol.
Imaging and Analysis Platform for Automatic Phenotyping and Trait Ranking of Plant Root Systems
The imaging and analysis of root growth is fundamental for the characterization of the root system architecture (RSA). Plant fitness and survival depend on RSA, which is, therefore, a major determinant of yield in crop plants. Modification of RSA also contributes to improvements of other desirable agronomic traits, such as tolerance against drought, salt, and nutrient deficiencies. Traditional methods of observing RSA, such as excavation or washed soil cores, destroy the topology of the root system and are not well suited for such analyses because of their invasive character. In contrast, there are newer nondestructive methods, such as X-ray computed tomography or imaging by magnetic resonance or nuclear magnetic resonance for the analysis of roots grown in soil. However, the application of these methods is mostly limited by different factors (e.g., high costs, difficulties in access to equipment, imaging time, container size, or resolution).
To circumvent these problems, Iyer-Pascuzzi et al. present a platform for the noninvasive automatic imaging and analysis of complex root systems. For this purpose, rice plants are grown in solid and transparent media in 2-L glass cylinders. After 14 days, the cylinders as placed on an automated turntable with a computer and a digital camera. Pictures of the roots are then taken from 20 angles, which takes about 10 min for each plant. After image preprocessing. several traits of root growth are determined and used for quantification of RSA. The described procedure enables the authors to establish an automatic image-analysis pipeline for the high-throughput analysis of complex root systems predominantly found in crops. In combination with support-by-vector-machine analysis, this platform makes it even more possible to use RSA data for quantitative trait locus experiments in which hundreds of plants must be imaged. The flexibility of this system in terms of species, traits and conditions, low costs, and speed will make a large contribution to increase crop productivity (Plant Physiol.
Genetic Screening Identifies Cyanogenesis-Deficient Mutants of Lotus japonicus and Reveals Enzymatic Specificity in Hydroxynitrile Glucoside Metabolism
Cyanogenesis, the release of hydrogen cyanide from damaged plant tissues, can limit the use of particular harvests for human or animal consumption. This happens as a result of enzymatic degradation of cyanogenic glucosides by ß-glucosidases in a number of crops. To circumvent this problem, adequate processing is required to remove cyanogenic glucosides from a number of forage grasses, legumes, and other crops before consumption by humans or cattle. Consequently, there is considerable interest in breeding lines of these species with low or even no cyanogenic content.
In this article, the authors report an HTS method to screen for mutants of Lotus japonicus with diminished cyanogenesis that easily can be adapted to other crops. The method is based on the colorimetric detection of HCN gas after a freeze-thaw cycle of a single leaf in 96-well microtiter-plates. Whatman 3MM paper is pretreated with a solution of tetra base (4,4'-methylenebis-(N, N-dimethylaniline)) and copper(II) ethylacetoacetate dissolved in chloroform. This paper is dried and placed between lid and microtiterplate for 3-h incubation time. It turns blue after oxidation of the tetra base when it comes in contact with the HCN gas that is produced. Normally, blue spots appear over wells with undisturbed cyanogenesis, and the coloring is weaker or even disappears over wells and leaves with inhibited formation of HCN.
The application of cyanide-sensitive paper, which was first described by Feigl and Anger (1966), enable the authors to screen 44,000 plants in high-throughput manner and to isolate mutants in reduced time. The establishment of this HTS method is an impressive example of the combination of classical analytical chemistry with novel investigative approaches to address actual questions and challenges in plant breeding. Because the described method can be adapted for other crops, it is very likely that this HTS approach for screening lines affected in cyanogenesis will find wide application (Plant Cell.
Automation Systems and Software
MS-LIMS, a Simple Yet Powerful Open-Source Laboratory Information Management System for MS-Driven Proteomics
MS-based proteomics produces large amounts of mass spectra that require processing, identification, and possibly quantification before interpretation can be undertaken. In literature, proteomic laboratories acquire millions of MS/MS spectra per proteome analysis to get large-scale proteome maps. High-throughput studies require automation of various workflow steps and data management in association with the results obtained. This article presents the so-called MS-LIMS (http://genesis.UGent.be/ms-lims), a freely available, open-source system. The client-server solution is based on a central structures query language database (such as my structures query language) and supports automated data management and processing in MS-driven proteomics analyses. The generic system concept, tool integrations, the IT functionalities of important steps of start-to-end workflows, and the contrast to other LIMS are discussed. MS-LIMS has been developed and used in international teamwork for more than 5 years (Proteomics
Using Laboratory Information Management Systems as Central Part of a Proteomics Data Workflow
This article considers data management in distributed applications of bioinformatics. The organization and storage of proteomic mass data are challenging issues today and even more challenging for the rising amount of information in the future. This review article describes the advantages of using LIMS in proteomic laboratories. Seven typical LIMS are explored in detail to describe their role in even greater interrelation. LIMS are discussed as a central IT component of proteomic data workflow, starting with data generation and ending with publication in journals and repositories. Storage of raw data and peak lists from MS-LIMS to store experimental parameters, data sets, and results, as well as analysis of quantitative and other data are discussed. Existing LIMS are reviewed with regard to their features and usability. A user definition of LIMS for proteomic data workflow and selection criteria for choosing the most interesting LIMS for proteomics are the purposes of this article (Proteomics
Liquid and Solid Delivery Technologies
Development and Characterization of a Cartridge-Type Pneumatic Dispenser with an Integrated Backflow Stopper
Today, there is an increasing demand for liquid delivery systems to handle volumes down to the nanoliter scale. Especially for biologic applications, these systems have to be built in a way that avoids cross-contamination. Sangmin Lee and Joonwon Kim propose a simple and low-cost, cross-contamination-free disposable dispenser that is able to dispense liquid samples between 100 and 400 nL. The system comprises a reservoir, a dispenser, and an active pneumatic actuation part. The reservoir can be of any kind, as long as its outlet opening is compatible with the dispenser. The dispenser is a cartridge-shaped part made from glass, silicon, and polydimethylsiloxane. These materials, state the authors, make the device harmless to most biosamples. It is, furthermore, designed in a way that does not need a valve to stop backflow. Hence, all contaminated parts of the system (reservoir and dispenser) can be manufactured at low cost and are disposable. To dispense, the reservoir and the cartridge dispenser are attached to the pneumatic actuator. The actuator applies pressure to the dispenser's membrane, which, in course, generates droplets. While the membrane forces the liquid toward the nozzle, it also closes the fluid path to the reservoir and stops backflow.
The system was validated by computer vision and weighting of accumulated droplets dispensed into an oil bath to prevent evaporation. The dispenser is able to dispense drops between 100 and 400 nL depending on the applied pressure. The pneumatic actuator is the only part equipped with expensive pneumatics and electronic control. It would be part of the robotic system, whereas the dispenser cartridge and the reservoir are disposable. In this way, it is possible to realize a very cost-efficient, robotic, cross-contamination-free liquid delivery system (J. Micromech. Microeng.
On-Demand Generation of Droplet in Size over a Wide Range by Microfluidic Control
Emulsification of liquids is an emerging technology and is, for example, used as an encapsulation of DNA or nanopar-ticles. Feng et al. describe the layout of a magnetically driven microtool (MMT) to produce emulsion droplets on a chip. MMTs are soft, and thus, do not harm cells being manipulated. A driving unit is needed to control the chip. The MMT uses two parallel plates and is, thereby, constrained in translational motion. By moving the microtool into the flow channel, the continuous phase can be cut into size-variable droplets, and the dispersed phase can inflow into the microchannels to produce size-controlled droplets on demand. The authors state that a novel hydraulic design enlarges the dynamic range of the droplet radius. It ranges from 40 to 180 μm. The correct function of the MMT is validated with olive oil and ethanol and with three different flow rates (Int. Symp. Micro-NanoMechatronics Human Sci., Nagoya (JP), 8-11.11.
Waveform Design Methods for Piezoelectric Ink-Jet Dispensers Based on Measured Meniscus Motion
Drop-on-Demand liquid handling systems used in the laboratory must be calibrated for every reagent. Kwon describes a new method to calibrate the system, that is, the voltage pulse that drives the piezo, which does not need to actually spot the reagent into waste. A setup in which a camera is coupled with light-emitting diodes that are synchronized with the jetting signal is described. It facilitates the observation of the meniscus at the nozzle tip if the pulse strength is chosen such that no drop formation occurs. The author shows that the meniscus motion depends on the fluid properties of the reagent and, hence, that a valid pulse waveform can be derived from it. He concludes that an efficient pulse waveform can be found, but that issues, such as satellite droplet and exact droplet volumes, cannot be handled yet (J. Microelectro-mech. Syst.
Footnotes