WO2009117032A2 - High throughput methods for analysis of contamination in environmental samples - Google Patents
High throughput methods for analysis of contamination in environmental samples Download PDFInfo
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- WO2009117032A2 WO2009117032A2 PCT/US2008/087498 US2008087498W WO2009117032A2 WO 2009117032 A2 WO2009117032 A2 WO 2009117032A2 US 2008087498 W US2008087498 W US 2008087498W WO 2009117032 A2 WO2009117032 A2 WO 2009117032A2
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
- G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
- G01N21/64—Fluorescence; Phosphorescence
- G01N21/645—Specially adapted constructive features of fluorimeters
- G01N21/6452—Individual samples arranged in a regular 2D-array, e.g. multiwell plates
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5025—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures for parallel transport of multiple samples
- B01L3/50255—Multi-well filtration
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
- G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
- G01N21/64—Fluorescence; Phosphorescence
- G01N21/6428—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes"
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/06—Fluid handling related problems
- B01L2200/0689—Sealing
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/04—Closures and closing means
- B01L2300/046—Function or devices integrated in the closure
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/08—Geometry, shape and general structure
- B01L2300/0809—Geometry, shape and general structure rectangular shaped
- B01L2300/0829—Multi-well plates; Microtitration plates
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/02—Burettes; Pipettes
- B01L3/0289—Apparatus for withdrawing or distributing predetermined quantities of fluid
- B01L3/0293—Apparatus for withdrawing or distributing predetermined quantities of fluid for liquids
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/24—Earth materials
Definitions
- the present invention relates to the detection of contaminants in environmental and industrial hygiene samples using high throughput methods. This method can be used to analyze environmental samples of soil, air, water, surfaces and any others for contamination by metals and compounds.
- Environmental and industrial hygiene samples originate from a number of places, such as industrial sites, waste storage and dumps, around these areas in air, water and soil, or those that may have been contaminated by terrorist, military or other acts.
- Some of the toxic industrial materials are lead, hexavalent chromium, cadmium, mercury and beryllium to name a few prominent ones. These materials are typically analyzed by extracting the toxin or the contaminant in a liquid medium (using acids, bases and other solvents and solutions) and then subjecting this to analysis.
- Typical analysis involves taking these samples and analyzing them sequentially through chromatography (e.g., high performance liquid or gas chromatography), inductively coupled plasma along with atomic emission or a mass spectrometer (ICP-AES and ICP-MS respectively).
- the samples are eluted into the equipment in a sequence with enough gaps or purges so that there is no cross-contamination.
- autosamplers have been developed for such instruments. In these the samples are put in a queue, and the samples are automatically analyzed one after the other.
- ICP-MS instruments 200 samples may be queued which may take 10 hours to analyze. This causes many issues related to the drift in baseline, and for proper quantification one may require calibration standards to be run periodically during this long analysis time.
- microarray and microwell formats are routinely used and are then analyzed by optical scanners (by looking for fluorescence, luminescence and absorption/transmission changes and quantifying these).
- Typical microwell formats have 24, 96, 384 or 1536 or more wells in an area of about 8cm x 13cm. Such plates can be read by the optical scanners in a matter of minutes.
- Microarrays may have thousands of analytical spots on a plate. Further, standards occupy some of the spots or wells so that they are all read almost simultaneously (within minutes) avoiding temporal drift.
- One object of the present invention is to demonstrate that environmental and industrial hygiene samples can be measured at high throughputs.
- Another objective of this invention is to enable processes so that environmental and industrial hygiene samples could be prepared with high degree of automation such that they are ready for analysis.
- Yet another objective is to automate the sample preparation and analysis so that high throughputs are achieved.
- the present invention provides a method of preparation of samples and their analysis at high throughputs. This reduces cost, increases efficiency and also reduces chemical waste generated during analysis.
- This invention is particularly applicable for environmental and industrial hygiene analysis (typically soil, water, air and surface) to analyze toxic elements such as lead, mercury, cadmium, arsenic, beryllium, thallium, antimony, uranium and selenium and other suitable toxic materials.
- Figure 1 Schematics of a 96 well plate array
- Figure 2 Schematics of automation for sample preparation for beryllium analysis by fluorescence
- Figure 3 Schematics of filtration step in automation
- Figure 4 Change in fluorescence emission for different concentrations of beryllium when excited by optical radiation of 385nm and a bandwidth of 20nm (i.e., ⁇ lOnm centered around 385nm);
- Figure 5 Excitation spectrum for the peak at 476nm and at 545nm for beryllium assay, the ratio of the two spectra is also provided;
- Figure 6 Emission spectra of a beryllium assay when the sample is excited by 385nm and by 390nm optical radiation, the band width for both is ⁇ lOnm.
- Beryllium is a metal that is used in a wide variety of industries including electronics, aerospace, defense, and the Department of Energy (DOE) complexes. Exposure to beryllium containing particles can lead to a lung disease called Chronic Beryllium Disease (CBD). Recent new regulations from DOE dictate a permissible exposure limit of 0.2 ⁇ g/m 3 in air, a housekeeping level of 3 ⁇ g/100cm 2 on a surface, and a release level for materials after beryllium exposure where the surface contamination due to beryllium must not exceed 0.2 ⁇ g/100cm 2 .
- CBD Chronic Beryllium Disease
- Optical analysis methods such as fluorescence, luminescence and absorption (or change in transmission) have been highly developed for high throughput analysis of biological samples.
- the fluorescent method for beryllium is well described in US patent 7,129,093 and US patent application 2005/0221498 and PCT application WO2008/130,737. All of these are incorporated herein by reference.
- Electron or x-ray induced fluorescence may also be used in an array format.
- the samples are typically made by putting probes on surfaces or liquid samples in plates with microwells. Examples of microarrays can be found in US patents 5,700,637; 5,744,305; and 7,195,872 and US patent application 2003/0027129. Microwells have been used for a long time in biological analysis.
- Typical plates with microwells are available in standard wells of 24, 96, 384 and 1536 (Fisher Scientific, Pittsburgh, PA) where a typical plate size is about 8x13 cm.
- Samples in array or microwells can provide a high throughput analysis if the test can be configured to take advantage of this in the field of analytical chemistry.
- Using an autosampler on an ICP instrument can take almost 6 hours to analyze 90 samples by either AES or MS (Mass Spectrometer), or even using atomic absorption spectrometer (AAS). During this period the calibration curves may shift and one may have to check these periodically extending the analysis time further.
- a plate with 96 wells (or samples) in a fluorescent system can be read in the order of a few minutes (usually less than 10 minutes, typically less than 1 minute). It is also preferred that some of the wells (typically 4 to 12) are occupied by the standards so that the standards are read at about the same time as the samples, and the unknown concentrations in the samples are detected by calibrating against the standards.
- the wells holding the calibration standards can be in a particular row or column or be distributed in any order within the plate. This is also different from conventional instruments, where the instrument has to be calibrated first in order to read the samples.
- Figure 1 shows a schematic of a 96 well plate.
- the rows and columns are designated by a matrix of letters and numbers.
- well B4 will be the well in the second row of the fourth column.
- standards can be in a column from Al to Hl or in A6 to H6, or in a row or in wells distributed throughout the plate. Some of these may be standards for calibration, while the others may be standards to check or verify the accuracy of the results, particularly if some of the results are extrapolated.
- the samples corresponding to 20 ⁇ g and 0.01 ⁇ g are also included to check the extrapolation outside the range of highest interest and to check the detection limit of the method respectively.
- Another way for large dynamic ranges is to calibrate on a log-log scale. Typically this is useful when the range of interest is more than two orders of magnitude (i.e., a difference of 100 times or more).
- a significant advantage of the optical method is the speed at which the plates or arrays can be read. This allows a laboratory to purchase a single machine which can process thousands of samples that replaces a bank of ICP machines which are highly expensive. Further, in the plate readers one can typically read in a number of formats, i.e. at different wavelengths or different modes such as fluorescence, absorbance, polarized fluorescence, etc.
- the false signals can be particularly strong when one is looking at ultralow concentrations, which are typically below lppb (parts per billion) in analytical solutions.
- the measurement solutions can turn yellow.
- the sample yellowness can be typically seen by looking at absorbance anywhere in the range of 400 to 450nm.
- an optical filter transmitting in this range can be used to check this.
- hydrophilic filters e.g. polyether sulfone and hydrophilic polypropylene
- the sample requirement of optical methods is small, thus a small fraction of the sample is used for analysis and the rest can be stored to re-check if necessary.
- most ICP methods may consume 5ml to 15ml of sample where as for optical methods less than 2ml is required and in many cases less than ImI.
- the 96 well plate readers typically use less than 0.3ml per well and 384 well plate readers use less than 0.05ml per well. This also allows one to put several replicates of samples on the same plate to get high statistical accuracy.
- syringes and probes fine tubes for aspirating in liquids and dispensing them from one place to the other should be made or coated with organic polymers.
- polystyrene resins e.g., polypropylene
- halogenated polymers e.g., polytetrafluoroethylene and fluorinated ethylene/propylene and polyvinylidene fluoride and polyvinylidene chloride
- polycarbonate e.g., polysulphone
- polyacetal and polyesters e.g., polyethylene terephthalate and ethylene naphthalate
- thermoset polymers such as epoxies and alkyd resins.
- these coatings should be placed both on the exterior and the interior surfaces of the probe, while for syringes only the interior surfaces are sufficient.
- the probes and the syringes are constructed out of the polymeric materials, with exemplary materials listed above.
- ASTM method D7458 is for bulk soil analysis. In this method 50ml of ammonium bifluoride (ABF) solution is dispensed for each sample and then this is processed by heating and after that only a fraction of a ml of the solution is needed to prepare the final analyte for analysis.
- ABSTM method D7458 is for bulk soil analysis. In this method 50ml of ammonium bifluoride (ABF) solution is dispensed for each sample and then this is processed by heating and after that only a fraction of a ml of the solution is needed to prepare the final analyte for analysis.
- ABSTM method D7458 is for bulk soil analysis. In this method 50ml of ammonium bifluoride (ABF) solution is disp
- these vials are large and several liters of ABF solution will be required, it is desirable to preserve space on the expensive multi-purpose robotic system and to speed the analysis, a separate simple robotic system is used where the liquid is pumped through for initial pumping of ABF. After processing these vials may be placed on the multipurpose robotic system for preparation of the analyte which requires filtration, mixing with other reagents and preparation of the plate with samples and standards. In case the space on the multipurpose robotic assembly is restricted, one may design a carousel that can feed one or more vials at a time so that the fluid from these can be picked up by the multipurpose robotic probes.
- the fluid handling systems may be optionally integrated with liquid level sensors, bar code readers, etc. in order to reduce manual checking and data entry.
- One may also include a station for automatically weighing the individual samples, where the samples (prior to positioning them in the plates) may be placed robotically.
- cappers and decappers For handling large numbers of samples it is also preferred to use cappers and decappers to easily tighten the caps and remove them from a multitude of bottles or vials used to process the samples.
- water is typically used as "system fluid” and for washing the reagents as it runs through the system.
- the "system fluid” is typically degassed before use so that air bubbles in the line do not cause loss of precision and reliability in dispensing which can interfere with the results.
- inline degassers be added at the point of entry of system fluid, or in line with each of the fluid channels.
- inline degassers are available from Phenomenex (Torrance, CA) under the brand name of Degassex.
- the present invention is concerned with preparation and analysis of arrays of samples for environmental analysis, which are prepared using automation and read quantitatively by optical methods or by ionizing radiation such as x-rays and electron beams. Typical regulation limits for these materials are summarized in Table 2.
- the contaminant is drawn from a solid matrix in a liquid solution (unless the contaminant is already in liquid, such as water). This is done either by dissolution (or extraction of the contaminant or components including the contaminant) or by dissolving of the solid.
- a liquid solution unless the contaminant is already in liquid, such as water.
- dissolution or extraction of the contaminant or components including the contaminant
- dissolving of the solid One may use solutions from known methods to totally digest the sample in order to get the analyte in the solution.
- the methods from Environmental Protection Agency (EPA) such as SW846-3051 and 3050, or OSHA125G or NIOSH 7300 use concentrated acid, such as nitric acid, which may be mixed with hydrogen peroxide and concentrated hydrochloric acid, or one may use ammonium bifluoride aqueous solution, as given in NIOSH procedures 7704 and 9110 or ASTM D7202 and D7458.
- EPA Environmental Protection Agency
- NIOSH method 7300 for beryllium calls for treating the samples with a mixture of perchloric and nitric acid on a hot plate at 120C. More of this acid is added after a small volume is left, and this is repeated several times until the solution is clear. This is then washed with distilled water and heated to dryness at 150C, and more acid solution is added to dilute the material to a specific amount and then used.
- ABF aqueous solution has been principally used for beryllium, it may also be used for extracting elemental toxins, such as antimony, lead, thallium, mercury, arsenic, cadmium, selenium, uranium and hexavalent chromium from the media (filter or a wipe) or soils.
- elemental toxins such as antimony, lead, thallium, mercury, arsenic, cadmium, selenium, uranium and hexavalent chromium
- the time of treatment, concentration of ABF, temperature of treatment and the ratio of ABF to the sample may vary. However, common protocols are always preferred for automation so that the costs can be reduced.
- ABF concentrations less than 20% in the solution and a temperature of less than IOOC are adequate for such extractions.
- the ratio of soil (or the amount of material on the media) to ABF in the solution is preferably less than 1.
- high fired beryllium oxide found in air or that deposits on surfaces in beryllium processing facilities can be dissoluted in 1%ABF at 8OC in half an hour in 5ml solution.
- Beryllium metal can be dissoluted at room temperature under similar conditions in 30 minutes.
- beryllium has to be analyzed in soil samples then for 0.5g of soil sample 3%ABF solution is required at 9OC for 40 hours, and 50ml of solution is required for half gram of soil samples with particle sizes less than 100 microns (Agrawal, A. et al, Environmental Science and Technology and ASTM test method D 7458).
- the solvents to extract the toxic metals are acidic in nature (pH is typically less than 4). Since the toxicity of ABF is lower as compared to the concoction of concentrated acids that are used to typically dissolute toxins for environmental and industrial hygiene applications, the use of ABF solutions is desirable.
- Multistep dissolution processes may also be automated, where in the dissolution step various optical end point checking techniques may be incorporated.
- simple absorption or transmittance measurement optics for example an LED with a detector may be combined
- the tubes may be located in an oven or a hotblock.
- the tubes may be capped and these may be decapped and capped automatically in order to add the reagents.
- Such cappers and decappers are available from FluidX (Cheshire, United Kingdom) and Par Systems (Shoreview, MN) and J-KEM Scientific, Inc (Saint Louis, MO)
- Automated liquid handling systems increase speed, provide consistency in sample preparation and lower cost by reducing the labor
- radioactive materials such as uranium and thorium it can also provide sample preparation without human intervention to increase the safety
- Hexavalent chromium in NIOSH method 7600 is conducted by dissolution of the chromium from an air filter in an acidic or a basic medium where one uses sulfuric acid to extract soluble chromates and sodium hydroxide and a sodium carbonate mixture to extract insoluble chromates particularly in the presence of reducing agents
- Lead can also be detected by optical means, e g , NIOSH analytical method 7700 This looks at development of red color and is a qualitative test However, using similar principles quantitative tests ha ⁇ e been developed such as Hach (Loveland, CO) LeadTrakTM system Use of multiwell plates for analysis and automated sample preparation can expedite any of such test procedures
- a sequence of automation steps for beryllium using NIOSH procedures 7704 and 9110 or ASTM D7202 involves the steps as shown in Fig 1, which involves preparation of a 96 well plate to be read in a fluorescence plate reader
- Step 1 The samples are typically provided in individual tubes which are usually capped These samples are placed on a rack of the automated system
- the format of the rack should be similar to the multiwall plate that would be made for measurement
- a typical format is a matrix of 8 by 12.
- This rack may be removable or it may be a hot block.
- Standards may be included in some of the positions on the rack if they will be processed along with the standards. Alternatively, some of the positions may be left blank if standards of known concentrations will be placed in the equivalent positions of the multi-well plate.
- Step 2 The samples in the tubes may be a filter paper or a wipe with the sample particles or it may be soil. If the tubes are capped they may be uncapped manually or automatically by the system. After decapping all or one at a time, ABF (dissolution) solution in a known quantity is added to all the tubes. The tubes are then capped (or capped one at a time after adding the reagent)
- Step 3 In case the hot block was used as a rack, the program to treat these tubes for a specified time and temperature is initiated, or the rack is temporarily removed for such processing elsewhere. After the samples are processed and cooled, the caps may be removed manually or automatically.
- Step 4 The system picks up a specified amount of the fluorescent dye solution from a vial or a tank (or it is run to the probe from the system) and then picks a specified amount of the sample solution from one of the sample tubes, preferably after introducing an air gap (between the two fluids).
- Step 5 The two fluids are simultaneously dispensed in a filter cartridge or in a deep well plate with filters placed at the bottom of each well.
- the fluids may be aspirated and de-aspirated several times for good mixing.
- the tip is then washed or disposed for the next sample, i.e. steps 4 and 5 are sequentially repeated for all of the samples.
- a filter cartridge is used for each individual solution then these are preferably arranged in a similar matrix as the well plates (e.g., 8x12 for 96 well plates), and if a deep well plate with filters is used then this also is preferably for a 8x12 format to go with the microwell plate.
- Step 6 If the samples are in individual filter tubes, these may be pressurized so as to filter the contents in a matrix of elution tubes or an elution plate located below the tubes or the filtration cartridge (which ever is used). In the latter typically vacuum is used between the filter and the elution plate for filtration. If any of the compartments in the filtration cartridge are empty they should be filled with a fluid in the same volume as the other wells with samples. A fluid of choice in this case is water.
- Step 7 After filtration, the filter tube rack or the filtration plate is removed so that the filtered fluids in the elution plate or the elution tubes is accessible to the probes.
- a specified quantity of filtrate is removed (typically same quantity for every sample) with disposable or a washable probe into a microwell plate. For 96 well plate this is typically between 100 to 300 ⁇ l and for a 384 well plate this is between 20 to 50 ⁇ l.
- Step 8 Add standards as needed to those micro wells in the plate that were reserved for this purpose, and the plate is inserted manually or automatically in a plate reader.
- standards can be pre-processed, i.e., one may provide a vial comprising a standard concentration which may be diluted in a serial fashion to make concentrations in a desired range. These serial dilutions are then mixed with the dye solution and then dropped on to the wells reserved for the standards in the same volumetric quantity as the samples. All this is done on the same equipment that is used for the sample processing above.
- the multiwall reading plate may be automatically inserted in the fluorescence reader or it may be done manually. In many of the automation platforms for biological work, one uses disposable plastic pipette tips or reusable metal probes.
- the step in which the toxin from the sample is extracted in a liquid media, acidic media or acids are generally used.
- Polymeric probes and tubings are preferred, some of the preferred materials are polyethylene, polypropylene, polytetrafluoroethylene and fluo ⁇ nated ethylene-propylene
- both the probe and the attached tubing are made out of a plastic and the length of the tubing is adjusted so that the fluids that are picked up by the probe are confined to the tubing only and do not enter the syringes which may have metal or glass parts
- the volume of the probe and the tubing is typically 50ml or less If metal probes are used they should be preferably coated with acid resistant organic coatings, especially any surface that will come in contact with the acidic solutions
- Preferred materials are organic polymeric coatings with low susceptibility to moisture absorption Some of these materials for coatings are polyethylene, polypropylene, polyvinyhdene chloride, parylene and fluo ⁇
- the preferred microwell plates for such analysis are those that have dark sides (preferably black) between the wells This ensures that there is no optical contamination of signals from the adjacent wells
- For fluorescence one may use black bottom plates or those with clear bottom In the former, the background fluorescence from the substrates is reduced
- the excitation source is from the top of the open wells
- the readout is from the top for fluorescence or from the bottom for fluorescence and absorbance Even with the clear bottoms
- these plates have high absorbance for the optical wavelengths used for exciting the fluorescence signal
- these plates may have UV absorbers to absorb the radiation below 400nm
- the wells be either coated with materials to modify the surface tension so that the fluid being analyzed wets the walls of the wells (i.e., the contact angle between
- Another important aspect of analyzing the well plates is the sensitivity of background to the particulate contaminants that may float on top of the wells giving rise to disturbance in meniscus and also adding to the fluorescent signal depending on the dirt.
- the automated processing of samples minimizes handling and reduces contamination probability. It is good practice to keep the plates covered when not in use, and handle them with gloves so that oils are not transported on to the plates, which may also add to fluorescence. Insects can have strong fluorescence, and one should examine the plates manually to ensure that bugs have not been trapped in the wells.
- the disturbance of the meniscus can also be reduced by adding surfactants to the solutions being analyzed.
- the plate may be agitated in order to wet the dirt and allow it to sink or minimize disturbances on the surface.
- a transparent plate in the optical range of excitation and emission, e.g. quartz
- quartz in order to protect the microwells from the dust and other particulates.
- Some of the coating methods employed for depositing hydrophilic coatings onto the plates is from vapors and liquids, including chemical vapor deposition processes assisted by plasma. These may be organic or inorganic. Some of the metal oxide coatings that provide hydrophilicity are comprised of silica and titania. These coatings may be comprised of carbon to enhance hydrophilicity. Hydrophilicity may be also imparted by introducing nanopores (pores less than lOOnm in size). One may use precursors such as tetra-orthoethylsilane, methyl triethoxy silane, and adjust the oxygen stoichiometry by introduction of oxygen and ozone (e.g., see WO/2007/021679).
- titanium tetraisopropoxide may be used to deposit hydrophilic coatings of oxide of titanium.
- silicon and titanium precursors may also be mixed (e.g., see Nakamura, et al). These coatings only need to be present near the top rim of the wells where the liquid forms the meniscus in the wells, thus it is not necessary for these coatings to uniformly coat the entire depth of the well. These coatings must be compatible with the solutions being analyzed and should not compromise the analytical aspects.
- the surfactants may also be added to the solutions being analyzed. These may be ionic (cationic or anionic) or non-ionic. These are preferably present in quantities of less than 0.1% of the solution volume, and preferably less than 0.01% so as to keep their interactions low.
- Some examples of such surfactants are Triton® XlOO, Triton® X-114, Triton® X-405, NovecTM FC4430, NovecTM FC4432, NovecTM FC4434. The first three are available from Aldrich Chemical Co (Milwaukee, WI) and the last three from 3M (Minneapolis, MN).
- a preferred dynamic range for beryllium quantification in surface wipes or air filter samples is less than 0.2 and more than 4 ⁇ g on the media, and a more preferred range is less than 0.02 and more than lO ⁇ g on the media and the most preferred range is less than or from 0.005 to 20 ⁇ g or more of beryllium on the media.
- This method has high flexibility to be tailored to any desired range. If higher amounts of beryllium are suspected that go beyond the instrument range, one always has the option to dilute the solutions or to use an optical filter to lower the excitation or the emission intensity.
- a preferred range is from about 0.1 ⁇ g of beryllium/g of soil to about 2000 ⁇ g of beryllium/g of soil, a more preferred range being from about 1 ⁇ g of beryllium/g of soil to about 200 ⁇ g of beryllium/g of soil.
- FIG 3 shows a preferred setup for filtration process
- the robotic arm of the automated instrument is shown as 31 that assembles and/or disassembles the filtration set-up
- the filtration setup comprises of a reservoir plate (37) with wells to contain the filtrate
- a housing (38) through O-rings (39) connects a filter plate (34).
- O-rings In some cases instead of "O" rings flat joints are also used. This is located with aligned individual filters cells, each having an individual filter (35). For filtration process, vacuum is pulled in the housing (from 30), so that the liquid passes through the filter and is collected in the reservoir plate (37).
- the vacuum is typically in the range of 25cm to 55cm of mercury, with a preferred range being 40 to 55cm of mercury.
- all the components above the plate 37 are removed robotically so that the liquid probes can access the filtrate (37a) in plate 37 and continue with the analysis. It is found that at the bottom of several of the filter plate tips a liquid droplet remains (as shown by 36). This is not acceptable, as during the removal of this plate after completing the filtering process, these drops may be released and contaminate liquid in the other wells in the reservoir plate 37. To overcome this, so that all the liquid is drained in the filtration process, we found that sealing the top of the wells in the filter plate (34) is important while the vacuum is pulled for the filtration step.
- sealing the wells properly may not require that all the wells in the filter plate 34 need to have fluid in them to balance out the resistance to flow in each well.
- membranes have been used to cover the top opening of the wells, but it does not effectively seal all the wells to the point that after filtration none of them have any droplets (36) left.
- vacuum assist devices available for microplates, such as those from Whatman (Florham Park, NJ) with a product number 7705-0112.
- This sealing problem can be accomplished by a plate with individual elastomeric plungers, or plungers with individual O-rings that can seal every well around the perimeter.
- a simple innovative way of overcoming this was by using a thin elastomeric sheet which is pressed against the wells.
- the cushion helps in transmiting the pressure applied to it uniformly to the first flexible membrane (32a).
- a preferred way to apply pressure is by a dead weight 32b (e.g. a plate with an appropriate mass).
- the cushion layer 32c is usually thicker than the element 32a, and may be made out of a flexible open cell foam, closed cell foam, gel or viscoelastic pad or an elastomer generally ranging in thickness from about 0.2cm and thicker, preferably thicker than 0.5cm.
- the element 32c may be bonded to the dead weight 32b.
- the characteristics of 32a are very important as it needs to seal each of the wells and be flexible so that it does not pucker or crease while sealing. We found good results with elastomeric sheets that were 40 durometer or less in hardness and a thickness less than lmm. More preferably durometer 20 or lower and a thickness of 0.5mm or lower.
- the element 32c transfers the force from the dead weight or another mechanism more uniformly onto 32a, but does not have to bend with the same degree of precision as element 32a.
- the thinness of 32a also compensates for any nicks, molding reliefs, flow welds around the well perimeters that are difficult to seal with a thick sheet.
- Another important parameter was the pressure on this elastomer film. This was greater than 2.5g /cm 2 and preferably greater than 1Og /cm 2 of the total filter plate area 34 (including the cross-section of the wells) as projected normally.
- 32a Some of the preferred materials of construction for 32a are silicone, polyurethane, Viton®, ethylene-propylene diene monomer (EDPM) elastomers, polybutadiene, fluoroelastomers, polychloroprene and polyisoprene.
- 32c can be constructed from a wide variety of materials including the ones described above for 32a as a solid material or as a foam including cellulosic materials and polyolefins (specific examples being, closed cell foams made out of polyethylene, silicone, polyurethanes and ethyl vinyl acetate).
- the foams should be preferably soft characterized by firmness, typically less than 25% deflection when subjected to a force of less than about 10 psi (typically tested using ASTM method D5672).
- the membrane 32a is not bonded to the upper members so that it can deform freely
- all members dead weight or pressure plate along with flexible elements other than membrane 32a
- it is preferred that all members (dead weight or pressure plate along with flexible elements other than membrane 32a) are bonded together Since the bonding assembly will be used several times it is important that all the bonded flexible materials have a high resiliency Membrane 32a may be replaced after each filtration step or it may be reused
- a preferred excitation a range is between 365 to 395nm This maximizes the emission signal response between 470 and 480nm and maintains good linearity
- an excitation filter transmitting at 385nm with a bandpass of equal or less than ⁇ 20nm, preferably less than or equal to ⁇ lOnm results in high excitation
- the peak transmission in the range of 470 to 480 with a bandpass of ⁇ lOnm is preferred
- a preferred filter will have a peak transmission at 475 nm with a bandpass of ⁇ 5nm
- the most preferred filter will have a plateau in the peak transmission area, with the transmission dropping to about 0% in about 2nm on either side of the curve
- the transmission at the peak should be preferably greater than 50%
- Another, factor that leads to improvement in ultra-low detection is reducing the background fluorescence Background fluorescence from the solution may be substantially reduced by using higher purity materials, such as lysine, that have low fluorescence
- the addition of this material to the chromium comprising samples can be accomplished in minutes and transferred to an automated shaker (several plate readers have built in shakers as well e.g., Biotek's (Winooski, VT)Synergy 2 instrument), and then all the samples analyzed within minutes, thus increasing the precision of the measurements.
- an automated shaker severe plate readers have built in shakers as well e.g., Biotek's (Winooski, VT)Synergy 2 instrument
- typical limits established by various agencies in air are from 0.1 to 0.001mg/m3.
- Example 1 Treatment of Stainless steel probes for increased corrosion resistance.
- Stainless Steel coupons were coated with parylene using a vapor deposition process.
- the type of parlyene used was "C” and the coating thickness was 2.5 microns.
- the coatings were deposited to MIL-I -46058C specifications by Advanced Coating (Rancho Cucamonga, CA).
- the coupons were tested in 3 weight % ammonium bifluoride at 25 and 90 0 C and after 48 hours showed a slight increase in there weight due to water uptake of the polymer coating. The results of the test are shown in Table 4 and show that after 48 hours the stainless steel coupons were completely protected from corrosion by the polymer coating In all cases the soaking solution remained colorless.
- Example 3 [0061] The NIOSH method 7704 and 9110 using fluorescence for detecting beryllium was adapted for a fluorescence reader using a 96 well plate.
- the reader was a BioTek Synergy 2 fluorescence plate reader and the plate was a Corning Costar 3915 flat bottom non-treated non-sterile, black, polystyrene 96 well assay plate.
- the plate format was such that the 8 wells in the first column contained the beryllium standards and the remaining wells contained the unknowns.
- the excitation filter used was 365 ⁇ 10nm and the emission filter was 476 ⁇ 3.5nm.
- the light source was a tungsten lamp and readings were taken from the top of the well (50 readings/ well) with a mirror optics position of 400nm.
- the standards used to calibrate the BioTek reader were 0, 0.1, 0.5, 2.0, 10.0, 40, 100.0 and 200.0 ppb and the volume in the well was 230 ⁇ L. These were plotted in a linear form and a regression fit was used to calculate the correlation value R. Values of R > 0.999 were considered a good fit.
- the 0, 0.5 2.0 10.0 and 40.0 ppb calibrants were prepared by a 2OX dilution of the following beryllium standards: 0, 10, 40, 200, 800ppb supplied by Spex CertiPrep Metuchen, New Jersey.
- calibrant preparation is as follows: 0.1ml of the Spex standard was dissolved in 1.9 ml of the dye detection solution (2OX dilution) and 230 ⁇ L of this solution was placed in the well. Some of the other standards from SPEX were diluted with 1% ABF and then diluted 2OX with the dye solution to obtain calibrants with 0.05, 0.1 and 200pp of beryllium. In these standards the source of beryllium was beryllium acetate.
- the samples in the plate were solutions containing known beryllium acetate concentrations in the range 0.05 to 200ppb.
- the complete 96 well plate was read in a dual format where samples with beryllium ⁇ 40ppb were read using a "Fine" standard calibration curve based on 0, 0.1, 0.5, 2.0, 10.0 and 40ppb standards and samples with "Coarse" beryllium content (> 40pb) where read using 40, 100 and 200ppb standards. This was achieved by programming the reader to read the well plate using the "Fine” and the "Coarse” standard calibration curves. For the "Fine” calibration reading the voltage was set at 145 volts which was equivalent to 1.76 million counts for the 40ppb standard.
- Table 5 Readings from a plate comprising of standards and samples
- a 96 well plate similar to that described in example 3 was read on the BioTek reader where the calibration curve used (standards same as in example 3) was plotted on a log-log scale. Using this scale all standards could be read in one reading which eliminated the need to do the dual scan of the low and high standards. For 50 reads/well the time to scan the plate was 4 minutes. For this reading the excitation filter was 365 ⁇ 5nm, the emission filter was 476 ⁇ 3.5nm and the sensitivity was set at 85V which is equivalent to 1.45 million counts for the 200ppb sample. The results for this analysis are summarized in Table 7 in terms of mean and standard deviation.
- Table 7 Mean and standard deviation for readings based on log-log standard calibration plot
- Example 5 To modify the wetting of the samples and standards in the polystyrene wells a surfactant, namely Triton-XIOO, available from Sigma- Aldrich (Milwaukee, WI), was added to the solutions. The surfactant was added to the detection solution in a concentration of 0.00045 weight%. The reading was performed as described in Example 3 using both the high (sensitivity 108V) and low (sensitivity 120V) standard method. The addition of the surfactant enhanced wetting of the wells and Table 8 shows a summary of the results for known samples at 0.1 and lOOppb.
- Triton-XIOO available from Sigma- Aldrich
- An automated filtration system was implemented using the current innovation on a JanusTM automated liquid handling workstation from Perkin Elmer (Waltham, MA) This system was used to automate the procedure for beryllium analysis by fluorescence as provided in the NIOSH and ASTM procedures for wipes and air filters.
- the vacuum filtration system was also provided by Perkin Elmer.
- the filter plate was a 96 well plate with well capacity of ImI each and used 0.2 ⁇ m hydrophilic polypropylene filters in these wells. This was purchased from Pall Corporation (Ann Arbor, MI) as AcroprepTM 96 Filter Plate (part number 5052).
- the filtrate was collected in a 96 well, 1 ml capacity plates from Corning (Corning, NY) in Costar® plates with a product number of 3959. To ensure that the filter process was clean, that is each of the well openings at the top were sealed, we used a thin silicone membrane (first flexible membrane) which was a durometer hardness of Shore AlO and a thickness of 0.25mm.
- the silicone first membrane was backed by a soft 6mm thick closed cell polyethylene foam sheet (stiffness was about 4-6psi for 25% deformation) and then with a 6mm thick Viton® sheet of durometer hardness 75 A along with a dead weight of 300g made out of aluminum, all of which had a cross-section area to cover the filter plate below without hitting the edge ridges of the filter plate. This combination also worked very well with a vacuum of about 53cm mercury.
- Viton® sheet as above and the PE foam as above were purchased with adhesive back. The Viton® was bonded to the steel plate and the foam sheet was bonded to the Viton®. This bonded combination with a thin silicone first membrane described above also worked very well.
- This invention is particularly useful when filtering those well plates, where the liquid levels in them is different, or in some no liquid is present. While this invention has been described as having preferred sequences, ranges, steps, materials, structures, features, and/or designs, it is understood that it is capable of further modifications, uses and/or adaptations of the invention following in general the principle of the invention, and including such departures from the present disclosure as those come within the known or customary practice in the art to which the invention pertains, and as may be applied to the central features hereinbefore set forth, and fall within the scope of the invention and of the limits of the appended claims.
Abstract
Description
Claims
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CA2707035A CA2707035A1 (en) | 2007-12-19 | 2008-12-18 | High throughput methods for analysis of contamination in environmental samples |
GB1009308A GB2468240A (en) | 2007-12-19 | 2008-12-18 | high throughput methods for analysis of contamination in environmental samples |
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US822907P | 2007-12-19 | 2007-12-19 | |
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CN102507554A (en) * | 2011-10-26 | 2012-06-20 | 华南理工大学 | Method for detecting beryllium content in water |
US8834954B2 (en) | 2009-05-13 | 2014-09-16 | Sio2 Medical Products, Inc. | Vessel inspection apparatus and methods |
US9272095B2 (en) | 2011-04-01 | 2016-03-01 | Sio2 Medical Products, Inc. | Vessels, contact surfaces, and coating and inspection apparatus and methods |
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Also Published As
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WO2009117032A3 (en) | 2009-12-30 |
GB201009308D0 (en) | 2010-07-21 |
CA2707035A1 (en) | 2009-09-24 |
GB2468240A (en) | 2010-09-01 |
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