Showing papers in "Journal of Laboratory Automation in 2002"
TL;DR: In addition to bioactive fluid dispensing, ink-jet based microdispensing allows integration of features (electronic, photonic, sensing, structural, etc.) that are not possible, or very difficult, with traditional photolithographic-based MEMS fabrication methods.
Abstract: Applications of microfluidics and MEMS (micro-electromechanical systems) technology are emerging in many areas of biological and life sciences. Non-contact microdispensing systems for accurate, high-throughput deposition of bioactive fluids can be an enabling technology for these applications. In addition to bioactive fluid dispensing, ink-jet based microdispensing allows integration of features (electronic, photonic, sensing, structural, etc.) that are not possible, or very difficult, with traditional photolithographic-based MEMS fabrication methods. Our single fluid and mutlifluid (MatrixJet™) piezoelectric microdispensers have been used for spot synthesis of peptides, production of microspheres to deliver drugs/biological materials, microprinting of biodegradable polymers for cell proliferation in tissue engineering requirements, and spot deposition for DNA, diagnostic immunoassay, antibody and protein arrays. We have created optical elements, sensors, and electrical interconnects by microdeposition of polymers and metal alloys. We have also demonstrated the integration of a reverse phase microcolumn within a piezoelectric dispenser for use in the fractionation of peptides for mass spectrometer analysis.
82 citations
54 citations
TL;DR: In this article, the authors explored the use of UV laser ablation micromachining to construct microfluidic devices in polymers, which can create microchannels rapidly and modify the resulting polymer surface in a single step.
Abstract: We have recently begun to explore the use of UV laser ablation micromachining to construct microfluidic devices in polymers. This technique can create microchannels rapidly and modify the resulting polymer surface in a single step. By ablating under different atmospheres, it is possible to alter both the surface chemistries and physical surface morphologies of the microchannels. We have employed electroosmotic flow measurements, chemical mapping, and optical microscopy to characterize the microfluidic devices. In addition, we have studied the parameters affecting the ablation, such as the laser wavelength, laser fluence, laser firing repetition rate, and the material being ablated.
39 citations
TL;DR: In this article, the authors present the implementation of cell assays on a microfluidic platform using disposable microfluideic chips, where cells are hydrodynamically focused and pass the fluorescence detector in single file.
Abstract: Lab-on-a-chip technology achieves a reduction of sample and reagent volume and automates complex laboratory processes Here, we present the implementation of cell assays on a microfluidic platform using disposable microfluidic chips The applications are based on the controlled movement of cells by pressure-driven flow inside networks of microfluidic channels Cells are hydrodynamically focused and pass the fluorescence detector in single file Initial applications are the determination of protein expression and apoptosis parameters The microfluidic system allows unattended measurement of six samples per chip Results obtained with the microfluidic chips showed good correlation with data obtained using a standard flow cytometer
33 citations
TL;DR: The strengths and weaknesses of several possible optimization methods, including the stochastic tunneling method, are discussed, particularly applied to protein structure prediction and receptor ligand docking.
Abstract: We discuss the use of stochastic optimization methods for biomolecular structure prediction, particularly applied to protein structure prediction and receptor ligand docking. After a brief introduction we give an overview of the dominating physical effects that are important for protein structure prediction and outline our strategy to address this problem. We discuss the strengths and weaknesses of several possible optimization methods, including the stochastic tunneling method. Finally we give examples of applications of this methodology both for protein structure prediction and receptor ligand docking.
19 citations
TL;DR: MagneSil™ Paramagnetic Particles are silica-paramagnetic particles with an affinity for nucleic acids under defined conditions as mentioned in this paper, and they can be altered to select nucleic acid types.
Abstract: MagneSil™ Paramagnetic Particles are silica-paramagnetic particles with an affinity for nucleic acids under defined conditions. Particle structure and solution composition can be altered to selecti...
18 citations
TL;DR: In this article, the authors present a microfluidic chip with unique properties yet to be fully exploited, such as negative control, signal acquisition from slow-conversion enzymes, translation of a time series into a single data point per compound, reagent adhesion in the channels, and fluid property mismatches.
Abstract: The push for higher throughput screening coupled with the desire to use smaller volumes of material has sparked the development of new technologies. Caliper Technologies, Corp. (Mountain View, CA) has designed a microfluidics chip with unique properties yet to be fully exploited. The translation from a traditional plate-based assay to a microfluidic chip format has provided insights into assay development, screening data requirements, and the technology itself. Running a screen with this new technology presented challenges in throughput, signal acquisition from slow-conversion enzymes, the provision for a negative control, the translation of a time series into a single data point per compound, reagent adhesion in the channels, and fluid property mismatches. Overcoming these obstacles has resulted in a simple, robust system with significant savings in reagent use. Measures to improve throughput and generalize the system will be discussed.
13 citations
TL;DR: This work has developed proprietary technologies for executing continuous flow assays in biochips which mimic human capillaries and presents an instrument capable of doing so in the form of a microfluidic enabling platform.
Abstract: We have developed proprietary technologies for executing continuous flow assays in biochips which mimic human capillaries. Such technologies are integral to the rapidly growing laboratory instrumentation sector for applications in drug discovery, biotechnology, medical diagnostics and environmental studies. A common link between all sectors is the movement toward miniaturization to increase throughput, accuracy and efficiency in the development of new drugs. The miniaturization process itself leads to a demand for new instruments and tools capable of handling microlitre quantities of biological fluids and reagents, thus, we present an instrument which is capable of doing so in the form of a microfluidic enabling platform.
13 citations
TL;DR: In this paper, the authors describe the automation of an imaging internal source laser desorption Fourier transform mass spectrometer (I2LD-FTMS) using a commercial data acquisition system.
Abstract: This paper describes the automation of an imaging internal source laser desorption Fourier transform mass spectrometer (I2LD-FTMS). The I2LD-FTMS consists of a laser-scanning device [Scott and Tremblay, Rev. Sci. Instrum. 2002, 73, 1108–1116] that has been integrated with a laboratory-built FTMS using a commercial data acquisition system (ThermoFinnigan FT/MS, Bremen, Germany). A new user interface has been developed in National Instrument's (Austin, Texas) graphical programming language LabVIEW to control the motors of the laser positioning system and the commercial FTMS data acquisition system. A feature of the FTMS software that allows the user to write macros in a scripting language is used creatively to our advantage in creating a mechanism to control the FTMS from outside its graphical user interface. The new user interface also allows the user to configure target locations. Automation of the data analysis along with data display using commercial graphing software is also described.
13 citations
TL;DR: This article describes the customization of a preparatory scale SFC system purchased from Berger Instruments, Inc., Newark, DE, with the ability to collect fractions into the same disposable test tubes and racks which are already employed in HPLC.
Abstract: Preparative Scale Supercritical Fluid Chromatography is emerging as a powerful alternative to HPLC for the purification and separation of complex chemical reaction mixtures. Advantages include greatly reduced solvent usage (and thus lower cost and environmental impact), higher throughput, and in some cases higher resolution. While there are commercially available prep SFC instruments, none currently offer all the features desired by many medicinal chemists engaged in the drug discovery process. These include: the ability to collect an unlimited number of fractions per sample with high recovery and negligible carryover, fully automated capacity to collect several hundred fractions, and the ability to collect fractions into the same disposable test tubes and racks which are already employed in HPLC. This article describes the customization of a preparatory scale SFC system purchased from Berger Instruments, Inc., Newark, DE. (a subsidiary Mettler-Toledo International, Inc., of Greifensee, Switzerland) in or...
11 citations
TL;DR: The simulation results for various electrode dimensions may serve as a general design rule for DEP devices and outline how the combination of forced convection and DEP allows for bacteria separation at increased flow rates.
Abstract: We present the simulation, development and experimental validation of a μ-concentrator based on dielectrophoresis, DEP. In a first step dielectrophoretic force fields of various electrodes are computed and compared. The simulation results for various electrode dimensions may serve as a general design rule for DEP devices. Favorable electrode designs were realized in gold on glass substrates. The performance of the DEP chips is validated by concentration of E.-Coli bacteria, a separation efficiency of 99.93% was achieved. Furthermore, we outline how the combination of forced convection and DEP allows for bacteria separation at increased flow rates.
TL;DR: In this article, the relationship between flexibility and throughput is examined in three very different industries, i.e., the bakery, high throughput screening (HTS) and mobile phone assembly.
Abstract: Over the past few years, there has been much discussion about transferring industrial technology to laboratories. While it is easy to look at the superficial similarities, it is more important to examine the different requirements of different industries. In this way, it is possible to identify the technologies and techniques that can be successfully transferred to the laboratory to improve performance.This paper takes three very different industries — the bakery, High Throughput Screening (HTS) and mobile phone assembly and examines their different requirements. These industries have been selected from among the many sectors where the RTS Group operates — thus allowing real data from a number of situations to be used.One of the most important areas in automation design is the relationship between flexibility and throughput. This paper focuses on this relationship and its influence over machine configuration when comparing the requirements of the different industries.
TL;DR: The quality of gene arrays is dependent on spotting pins for production of uniform spots, which are consistent and consistent as discussed by the authors, which is not the case in the case of microarraying.
Abstract: Microarraying technologies have emerged as key tools for determining genomic expression. The quality of gene arrays is reliant on spotting pins for production of uniform spots, which are consistent...
TL;DR: A reagent system and robotic methods for the purification of PCR fragments from other contaminating amplification reaction components using the MagneSil™ paramagnetic particle chemistry to isolate double stranded DNA fragments from 150bp to 23kbp are described.
Abstract: Here we describe a reagent system and robotic methods for the purification of PCR (a) fragments from other contaminating amplification reaction components. The methods use the MagneSil ™ paramagnetic particle chemistry (b) to isolate double stranded DNA fragments from 150bp to 23kbp. Purified fragments are eluted in water ready for downstream applications such as cloning, fluorescent DNA sequencing and microarray printing. This method has been adapted to a number of liquid handling robotic platforms, including the Biomek ® FX and Biomek ® 2000 Laboratory Automation Workstations, in both 96 and 384-well formats.
TL;DR: The article describes the new proprietary spot-on™ technology developed by Allegro Technologies, Ltd., for nanolitre and microlitre dispensing of liquids for the drug discovery, genomics and proteomics industries.
Abstract: The article describes the new proprietary spot-on™ technology developed by Allegro Technologies, Ltd., for nanolitre and microlitre dispensing of liquids for the drug discovery, genomics and proteo...
TL;DR: In this paper, a glass microdevice for both electro-osmotic indirect pumping (EOIP) and EOP using porous barriers is presented, where electrical contact between the main and side channels is achieved by electrical breakdown.
Abstract: The manipulation of liquids within a microcapillary network
remains a considerable challenge in the development
of miniaturized total chemical analysis systems
(μTAS). Fluid manipulation can be achieved using (micro)
mechanical pumps connected or integrated into the device, and by
using an electric field (E) for generation of electro-osmotic flow
(EOF). For glass microdevices, electro-osmotic pumping (EOP) is
most attractive, since no moving parts and/or valves are required.
In its simplest embodiment, EOP in microfluidic devices
involves imposing an E along the full length of the channel by
immersing electrodes into open solution reservoirs situated at both
ends of the channel. Electrolytically generated gases at the electrodes
drift to the surface of the solution reservoirs and escape into the air.
In more complex situations, however, EOP in a subsection of a
microchannel may be required. For sampling, for example, from
brain tissue in living organisms, the presence of electrodes in the
‘sample reservoir’ (i.e., the brain), and thus outside the microdevice
is undesirable, since potentials applied to external electrodes interfere
with the sampling environment. In these cases, electrodes need
to be integrated into the microfluidic device. The use of electrodes
in a microchannel, however, is not trivial. Electrolytic gases get
caught in the sealed microchannel and hence effectively interrupt
the electric field, and thus fluid movement. A number of
approaches to avoid bubble formation during spatially localized
application of voltages in microfluidic networks have been
reported. In one example, a 1-mm-thick poly(dimethylsiloxane)
(PDMS) substrate containing the microchannel was sealed with a
glass cover plate containing the electrodes.1 Electrolytic gases
formed at the electrodes dissipated through the highly gas-permeable
PDMS film into the air.
An alternative method for application of the electric field is the
use of a conducting barrier between the electrodes and the channel.
A Nafion membrane has been presented as an interface
between an open reservoir containing the electrode and a
microchannel.2 Electrolytic gases dissipate into the air via the open
reservoir, while the electrical contact afforded by the membrane
ensured that an E was applied to the closed microchannel. A similar
approach involves the use of adjacent side channels, which are
electrically connected, via porous barriers, but where fluid
exchange is strongly limited.3,4 Either the porous membrane was
formed using a thin layer of potassium silicate, in or the contact
was directly over the glass wall separating adjacent channels.
The three approaches mentioned above allow the creation of
field-free zones in addition to regions where the field is applied. In
the field-free regions, charge-independent fluid transport can be
controlled by EOP elsewhere in the microfluidic system, an effect
we term “electro-osmotic indirect pumping” (EOIP) to distinguish
between EOP in- and outside the electric field.
In this paper, a glass microdevice for both EOP and EOIP using
electrically connected side channels is presented. Electrical contact
between the main and side channels is achieved by electrical breakdown
of the glass barrier between these channels. Electrical breakdown
for initiating liquid contact between disconnected channels
has been demonstrated in PDMS devices.5 To our knowledge, this
is the first time that electrical breakdown for initiation of electrical
contact between glass microchannels is presented. Cross injection
by a combination of EOP and EOIP is demonstrated.
Abstract: An automated instrument was designed and constructed to facilitate the performance of pharmaceutical degradation studies. A brief theoretical background on degradation kinetics is given to rationalize the design of the instrument and representative data are provided to illustrate its successful application. This system was found to be capable of conducting multiple simultaneous isothermal and nonisothermal kinetic studies with user-defined temperature profiles, sampling periods, and data logging.
TL;DR: A survey of directors of screening organizations was conducted in 2001 to evaluate their perceptions of the current vs. desired state of high-throughput screening (HTS) automation.
Abstract: A survey of directors of screening organizations was conducted in 2001 to evaluate their perceptions of the current vs. desired state of high-throughput screening (HTS) automation. The survey encom...
TL;DR: In this paper, the position of a compound along the linear support encodes its synthetic history, which can be used for full library analysis in the context of combinatorial chemistry.
Abstract: We have developed a novel method for combinatorial chemistry that allows for fully parallel synthesis and full library analysis. The key feature is the use of linear supports for synthesis, where the position of a compound along the support encodes its synthetic history. Use of an optical fiber as the linear support allows for the optical evaluation of libraries: the location of an emitting fluorophore can be determined using fluorescent optical time domain reflectometry. We have demonstrated that limitations on the spatial resolution imposed by the fluorescence lifetimes are overcome by using a second fiber as an optical delay.
TL;DR: Green fluorescent protein (GFP) has many applications as a marker in living cells, and has become widely used as a reporter gene in microbial, plant and animal cells.
Abstract: Green fluorescent protein (GFP) has many applications as a marker in living cells, and has become widely used as a reporter gene in microbial, plant and animal cells. Screening microbial colonies f...
TL;DR: A custom system for reading 2-D DataMatrix bar codes imprinted on the base of tubes stored in a rack is described and an example is given that illustrates how to call the custom software from Microsoft® Excel and insert the returned data directly into a spreadsheet.
Abstract: We describe the development of a custom system for reading 2-D DataMatrix bar codes imprinted on the base of tubes stored in a rack. The system software drives a standard flatbed scanner in order to acquire an image, interprets DataMatrix bar codes at predefined locations in the image, and returns in an array the interpreted bar code data along with other associated information. Commercial software components were used for the image acquisition and bar code interpretation portion of the software. An example is given that illustrates how to call the custom software from Microsoft® Excel and insert the returned data directly into a spreadsheet.
TL;DR: In this paper, induction based fluidics (IBFluidics) is used for transporting liquids in the micro and the macro world, where electric fields are shown to energize liquid/s in a container/s to execute an array of purposes.
Abstract: Induction based fluidics (IBF), a new, simple patented approach for transporting liquids in the micro and the macro world, is discussed. Electric fields are shown to energize liquid/s in a container/s to execute an array of purposes. IBF is shown uniquely to energize N liquids in simple off the shelf devices, inductively. We discuss calibration and other issues, as we demonstrate how simple devices can dispense nanoliters and microliters with high precision and accuracy. Furthermore, we show preliminary single and eight channel data for the Zip Tip™ made by Millipore where the device transports liquids “electrically.” We briefly consider how such new devices, “electric” Zip Tips™, might automate desalting and the placement of digests for MALDI TOF analysis.
TL;DR: An automated system is reported here the development of an automated system, the MegaMate, for carrying out high throughput (over 100,000 clones per day) yeast two-hybrid screens with full data tracking.
Abstract: Protein-protein interactions are a vital component in both the function and regulation of virtually all biological processes. In the yeast two-hybrid system, one of the most commonly-used methods for studying protein-protein interactions, protein-protein interactions are detected by expression of a reporter gene driven by the interaction between bait and prey proteins. We report here the development of an automated system, the MegaMate, for carrying out high throughput (over 100,000 clones per day) yeast two-hybrid screens with full data tracking.
TL;DR: The μFill, a 96-/384-well microplate reagent dispenser capable of running stand-alone or computer-controlled as part of a robotics system, and the microprocessor-controlled syringe pump, based on a tested, low-maintenance design that requires no calibration, yet provides a high degree of accuracy and precision.
Abstract: Today's biomedical research requires instrumentation that is both functional and versatile. While high throughput screening (HTS) and drug discovery laboratories require instrumentation that can be automated, pilot assay laboratories may not necessarily need total automation. Towards that end, Bio-Tek has developed the μFill, a 96-/384-well microplate reagent dispenser capable of running stand-alone or computer-controlled as part of a robotics system. The μFill is compatible with both 96- and 384-well microplates, and using a specially designed adaptor can also dispense to deep-well microplates. It is capable of dispensing from 10–3000 μl for 96-well plates and 5–1500 μl for 384-well plates in 1-μl increments. The μFill can dispense 20 μl into a 96-well plate in four seconds and into a 384-well microplate in 12 seconds. The microprocessor-controlled syringe pump is based on a tested, low-maintenance design that requires no calibration, yet provides a high degree of accuracy and precision. The accuracy wit...