Pipetting robots

The sample throughput of nanoESI is limited by the comparatively time-consuming procedure of manual capillary loading. A chip-based nanoESI sprayer on an etched silicon wafer allows for the automated loading of the sprayer array by a pipetting robot (Fig. 11.7). The chip provides a 10 x 10 array of nanoESI... 

NMR-tomographic method, any commercially available NMR spectrometer can be used. To inject samples from 384-format deep-well microtiter plates into the bundle automatically, an in-house-developed pipetting robot with a modified tray was used. 

Pipetting robot, e. g., Genesis, and Gemini and Facts software (Tecan, Maenne-dorf, Switzerland)... 

The micro-mixer is supplied continuously with two carrier fluids, either two immiscible liquids or a gas and a liquid. During screening, pulses of the dissolved catalyst to be screened and the substrate are injected simultaneously by a pipetting robot. The pulses are then mixed in a micro-mixer and form short defined reacting segments that move along the tubular reactor. 

The authors applied this concept to both gas/liquid (see Figure 3.75) and liquid/ liquid systems (see Figure 3.76). This set-up consisted in the core of a tubular reactor with an interdigital micro mixer as dispersion unit (compare Figure 3.77). The peripheral equipment consisted of an automated pipetting robot, a fraction collector and a gas-chromatograph equipped with an automatic injector. 

Once the final compound has been cleaved from the solid support, the contents of the blocks are drained into a standard 96-well microtiter plate. The solvent is removed in a vacuum oven and appropriate daughter plates (master chemistry plate, master biology plate and analytical plate) are prepared using a 96-channel pipetting robot. The average production capacity of such a work station is between 1000 and 2000 single spatially dispersed compounds per day. 

Avdeef introduced an alternative approach. Aliquots of DMSO stock solutions are pipetted robotically into incubation well plate containing an aqueous buffer. The concentration of the test compound should be between 50-150 iM in order to keep the DMSO content below 0.5 %. After a time of incubation, the plate is filtered and the solved compound is quantified with an UV plate reader. The method is fast, robust and reported to be reliable (Kerns). 200-300 compounds can be measured per day. Additionally, pH solubility profiles can be set up easily (Kibbey). 

Numerous modifications are in place at each lab regarding incubation conditions like substrate concentration, incubation time, cofactor use and concentration, protein concentration etc. These modifications depend on the purpose of the method, e.g. as a high through-put screen in early drug discovery or as a tool to characterize a development compound in vitro for regulatory files. Besides these modifications on the biological part of the assay, specific protocols on pipetting robots and conditions used for evaluation by LC-MS/MS also in combination with the instrumental equipment available are applied which are typically not published. Besides LC-MS/MS also LC-UV (Shearer 2002 Stratford 1999) and capillary electrophoresis (Clohs et al. 2002) are described. 

Pipetting stations may be used to automate an analytical procedure for which an automated analyzer does not exist or cannot be cost justified. Most pipetting robots are relatively easy to program, rarely malfunction, and can deliver liquids with extreme precision and accuracy. Multiple-channel pipetting robots allow parallel processing of specimens with 8- or 12-channel probes to handle microtiter plates. 

A similar experiment was performed in a 96-well plate format. The components of the polymerization mixture were the same except for the solvent (CH3CN was used instead of CH2C12). The polymerization was thermally initiated. The solutions were dispensed using a pipetting robot (Fig. 7.7) and the supernatants analyzed in series by HPLC-UV or in parallel with a plate reader. Eleven WellMIPs were prepared and screened for each monomer. As seen in Fig. 7.9, the reproducibility of the automated procedure is good and the fast parallel assessment delivers similar results as the serial analysis by HPLC. 

The array presented is applicable for resistive as well as for capacitive measurements. In addition, the design allows efficient and automated pipetting, robot assisted sample preparation and coating. 

Another inexpensive approach that can be automated with the aid of a standard pipetting robot is to use cartridges equipped with a hydrophobic membrane that allows a heavy organic phase to pass but retains the aqueous phase (Whatman, Separtis). It is even possible to separate emulsions. These membrane materials are also available in bulk and various shapes. An obvious Hmitation is that only solvents with a higher density than water, i.e. chlorinated solvents, can be used. 

Before or during any synthesis involving solid supports, the appropriate amount of solid support must be dispensed into each reaction vessel. With increasing numbers of reaction vessels, this becomes quite labor-intensive and tedious. While it is possible to use a manual pipette or a pipetting robot and suspensions of resin in isopycnic solvent mixtures, other methods and devices for dry dispensing have come to the fore. 

Zinsser market automated resin dispensers that employ powder dispensing technology borrowed from the pharmaceutical industry. As a stand-alone device (REDI) or integrated in a standard pipetting robot (LIFOS, Eig. 13), a vacuum pipette with adjustable tips is used that is available in various sizes. Typical reproducibility is specified at 2 % for 50 mg and 1 % for 150 mg of support With one tip, resin can be dispensed, for example, into the 96 wells of a microtiter plate within about 15 min. 

Pipetting robots to distribute synthesis building blocks, reagents, and solvents... 

Until today, most of the revenue in the field of lab-on-a-chip is created on a business-to-business, but not on a business-to-consumer basis [21], as the vast majority of research in the field only approaches the stage of demonstrators and is not followed by the development of products for end-users. Among the hurdles for market entry are high initial investments and running fabrication costs [22]. Furthermore, the multitude of individual lab-on-a-chip solutions developed so far cannot compete with the flexibility of state of the art liquid handling approaches, e.g. with pipetting robots. 

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