Pittcon 2018: An Illuminating Ride

Pittcon continues to be an important event on our calendar. Year after year, innovative products and technologies are unveiled, both by pioneers in the field and new companies just starting out.

Of note at Pittcon 2018 were the new NEXUS Theaters on the expo floor, where attendees could view product or sales presentations, and the Lab Gauntlet—a series of task-oriented challenges that connect attendees with exhibitors.

This year’s meeting was a remarkable departure from my previous 50 visits. For the first time, the exposition was held over three days instead of four. In addition, the technical focus of Pittcon has shifted. During the 1960s, the highlights were on spectroscopy (NMR and optical). The exponential growth phase of separation science was in the spotlight for the next four decades. But as HPLC and GC rapidly matured in 2000–2018, attention slowly turned to optical spectroscopy, high-resolution mass spectrometry, and informatics.

Liquid-phase separations

Liquid-phase separations are more than liquid chromatography. Centrifuges are used by tens of thousands, but users of electrical asymmetric field-flow fractionation (FFF) probably number less than 20 globally. Liquid chromatography, including ultrahigh-performance LC (UHPLC) and supercritical fluid chromatography (SFC), are of highest interest, at least to Pittcon attendees. So that is a place to start. Exhibition introductions focused on dual-channel LC and portable LCs.

Dual-channel liquid chromatographs for the laboratory

Three new LC instruments were on the floor. Each featured “dual technology” of some sort, but when I got into the details, the purpose and execution were quite different.

ACQUITY Arc Bio System

In 2015, Waters introduced the ACQUITY Arc UHPLC System, which was designed to aid chromatographers in bridging the performance gap between HPLC (~6000 psi) technology and low-dispersion UPLC (~15,000 psi) instruments. The stainless-steel ACQUITY Arc was outstandingly successful, with more than 2000 instruments placed within the first two years on market. Half of these are in Asia. Regulatory authorities accept such bridging studies.

This year, Waters introduced the ACQUITY Arc Bio System. Its distinguishing feature is its selectable dwell volume, which enables the system to emulate the dwell volume and mixing behavior of a number of LC systems. Additionally, the ACQUITY Arc Bio’s liquid flow path is iron-free, bio-inert, and capable of forming quaternary gradient elution using Waters Auto-Blend Plus technology. The target need niche is method transfer and method development of iron-sensitive analytes, especially using ion exchange, hydrophobic interaction chromatography (HIC), and steric exclusion separation modes. Since gradient elution is often used in bioseparations, Waters developed a Quantum Synchronization routine that starts the gradient run with the same run-to-run flow path conditions, including piston timing, which improves reproducibility.

ACQUITY Arc Bio System’s pump is rated at 9500 psi with an Fmax of 5.00 mL/min. This decrease in Pmax and increase in Fmax compared to the original ACQUITY UPLC reflect the difference in “sweet point” of column technology used in bioseparations.

An optional integrated mobile phase selector enables the addition of six more reservoirs to feed the column pump. With all these, one should seldom need to manually prepare complex mobile phases. For example, chromatographers can dial in the pH of the mobile phase with 0.1-pH unit accuracy and have the machine blend to the desired conditions. The pH range is 1–12.5.

Other specifications: total instrument band spreading is <30 µL for 4σ. Dwell volume for flow path 1 is <1450 µL. Gradient delay volume is <1050 µL. Flow path 2 has a dwell volume of <1150 µL and gradient delay of <750 µL. The difference is mainly the size of the gradient mixer.

Vanquish Duo UHPLC

Thermo Fisher Scientific extended the Vanquish UHPLC product line by adding the Vanquish Duo UHPLC. Cited advantages include:

  1. Running two assays simultaneously and independently. This doubles productivity, improves flexibility, and reduces footprint by 50%.
  2. When using gradient elution with MS detection, utilization of the MS can be low due to the long column regeneration cycle. With the Duo, assays can be run using two columns—while one is running, the other can be simultaneously regenerated. This doubles utilization of the MS. HPLCs are expensive, but generally, high-resolution MS systems are more so.
  3. The unique charged aerosol detector (CAD) works best when the composition and flow of mobile phase are constant. Thermo scientists developed a reverse gradient generated in the second channel to provide a constant-composition mobile phase to the CAD. One channel runs the analytical gradient separation in the usual manner, and the second runs the reverse gradient profile. Postcolumn, the mobile phase streams are combined just ahead of the CAD. Thus, the CAD sees a constant mobile phase composition, which gives a flat baseline. The Duo even calculates and compensates for liquid volume in the reference leg so a second column does not need to be used in the reference flow path.

ICS-6000 HPIC

The Dionex ICS-6000 HPIC (Thermo Fisher Scientific) ion chromatography (IC) instrument has a modular design that supports a wide range of liquid processing options combined with a range of detectors, including MS (Orbitrap or quadrupole), inductively coupled plasma (ICP)/MS, pulsed amperometric detection (PAD), UV absorbance, and suppressed conductivity. The pumps are rated to 5000 psi, which is sufficient for most IC columns packed with 4-µm particles in 4 mm to capillary diameter. The ICS-6000 has two pumps that support dual-channel operation for highest throughput. A novel maintenance-free suppressor module is also available. When access to the plumbing is required, the instrument opens to provide unfettered access to the interior.

The ICS-6000 records as many as 16 performance metrics on the columns and instrument to help the lab adopt the Internet of Things (IoT). It keeps track of 25 consumables and compares performance to new specifications. A tablet is an attractive user interface.

In ion chromatography, background suppression is used to remove buffer components from the column effluent, which improves signal-to-noise. Traditionally, electronic suppressors operated in a constant current mode. This year, Dionex introduced the DRS 600 Dynamically Regenerated Suppressor, which uses constant voltage. Constant voltage self-adjusts the current. The net effect is that peak-to-peak baseline noise is reduced by about 4–10-fold.

Portable LCs

Laboratory LCs are invariably large, heavy instruments. As LC technology matures, it is predictable, and hence unpatentable, that technology will evolve to make the instruments smaller. Feature and benefit studies predict that more compact size will improve portability and/or interfacing with hyphenated instruments such as LC-MS. At Pittcon 2018, there were examples of both.

Smart LifeLC

Previously, PolyLC had focused on analytical LC columns, primarily for hydrophilic interaction LC (HILIC). The general-purpose Smart LifeLC is mounted in a briefcase-sized clamshell housing that contains the mobile phase and waste reservoirs, binary pumps, and 255-nm LED absorbance detector and injection valve. The pumps are rated to 3000 psi over a flow range of 0.001–5 mL/min. For site or fieldwork, the external battery pack is sufficient for 9 hours of operation. Should repairs be required, the instrument can be returned to the factory for servicing.

Dr. Andy Alpert, PolyLC’s founder and president, has an entrepreneurial spirit and knows the diabetes diagnostic market well. This explains why the company’s first LC analyzer is for hemoglobin A1c, a diabetes marker. The instrument uses a 415-nm fixed-wavelength light-emitting diode (LED) detector and PolyLC columns.

Capillary LC

For the last few years, I’d reported that capillary HPLC was on the cusp of startling advances. After all, Dionex introduced the IC Cube for capillary ion chromatography five years ago. Two years ago at Pittcon, Prof. Milton Lee discussed a prototype capillary LC fluidics system. Last year, Sam Stearns, also a noted science-based entrepreneur, presented on the same topic during the opening lecture session on Sunday.

Focus LC

Just before Pittcon opened, I received an e-mail announcing startup Axcend’s unveiling of the Focus LC. It was referred to as “a toaster-sized gradient, nanoflow liquid chromatograph that weighs under 6 kg.” Prof. Lee’s prototype thus came to fruition.

The portable instrument weighs only 12 lb, including internal battery and eluent and waste reservoirs. Dual pumps provide gradient elution; dual UV/VIS LED detectors provide a 100× improvement in detection limits over traditional LCs, and waste is reduced by 1/500. This makes it possible to operate the Focus on a milliliter or two per day compared to half a liter per shift for a 4.6-mm-i.d. column running at 1 mL/min.

Dead volume in fittings is the major bug in capillary chromatography, be it gas or liquid. Axcend has designed a novel capillary cartridge that snaps and holds the columns aligned and in place. No tools are required. Data is stored in the instrument until it can be uploaded to the enterprise data system or cloud via USB or secure Wi-Fi using an HTML5 link.

Capillary LCs shrink the column dimensions, which seems to permit a reduction in instrument size. Where is size important? Portability enabling at-site analysis is one instance.

Capillary LC for MS

Locating the LC separation module to the ion source of mass spectrometers is another opportunity. In contrast to Axcend, VICI intends to focus on the LC/MS market, where small size facilitates locating the capillary LC or UHPLC immediately adjacent to the ion source. Trash the transfer lines! Nanospray should be a cinch.

MFx Collector

Preparative LC traditionally used fraction collectors that collected sample in multimilliliter test tubes or large vials. The LEAP Technologies MFx Collector (which is built on the PAL system) from Trajan Scientific and Medical is designed to work with smaller fractions employing zero-loss and zero-drip features that focus on getting the first and last drop from an analytical-scale HPLC. It even collects sub-2-second fractions in 384-well plates. A unique dynamic flow reservoir expands when the head is moving between collection receivers. Cut points are sharp without sample loss.

Columns for LC and SFC

BioResolve RP mAb columns

Antibodies and major fragments and synthetic constructs are frequent analytes. Waters developed a new wider-pore (450-Å) solid-core particle with an o.d. of 2.7 µm diameter. The first surface chemistry is polyphenyl. Applications support shows that the columns are suitable for antibody–drug conjugates, antibodies, and major fragments such as Fc and Fab. Run-to-run carryover is negligible.

Columns for antibody characterization

The Shodex PROTEIN LW-803 is the latest in a series of columns for steric exclusion chromatography. It is designed for the separation of monomer, dimer, and higher ’mers of antibodies in aqueous mobile phases. The column is 300 mm × 8 mm i.d. packed with 3-µm particles.

Switching the focus to oligonucleotides, Shodex introduced HILICpak VN-50 2D series. The column packing starts with 5-µm polyvinyl alcohol particles (100-Å pore) with a diol surface chemistry. The stationary phase is stable in the range of pH 2–13 and up to 60 °C. Solvent compatibility includes water, acetonitrile, and methanol. Column hardware is PEEK. Bleed is low, and ion pairing is not required, permitting MS detection.

Rapid separations are finally available for gel permeation chromatography of industrial polymers with the Shodex GPC-HK series. The column packing is a polystyrene/divinylbenzene copolymer with very narrow size distribution. This improves resolution compared to conventional column packings. Three pore sizes and operating ranges are available. HK404L has an operating range for polystyrene from 100 Da to 1 million Da. HK401 is for low-MW polymers in the range of 100–1500 Da. HK405 covers the range from 10,000 Da to 2.5 MDa. The columns are compatible with common solvents such as THF, CHCl3, DMF, and toluene. Shodex also has a related column (HFIP404L) suitable for engineered plastics, including polyacrylamide and PET, which require hexafluoroisopropanol (HFIP) as eluent.

SFC columns

Kromasil SFC-XT

Kromasil SFC-XT from AkzoNobel is a new column packing with a fused organosilane with significantly different retention than existing column packings designed for SFC. AkzoNobel also extended the range of columns and particle sizes of SFC columns to include organosilane, 2-ethylpyridine, silica, cyano, and diol bonded to 2.5- and 5-µm spherical organosilica particle with 100-Å pore.

Celeris

Celeris is a new line of columns from Regis Technologies for nonchiral separations using SFC. Surface chemistries include 2-ethyl pyridine, 4-ethyl pyridine amino, polyethyleneimine (PEI), and arginine.

Lab-scale glass columns

YMC introduced a line of lab-scale glass columns designed for biochromatography. Applications include research (5 mm i.d.) to pilot scale (600 mm). The company also introduced a new stationary phase for analytical chiral chromatography. The surface chemistry is “SJ cellulose” coated or bonded to 3-, 5-, 10-, and 20-µm particles.

Characterization of charged nanoparticles

Conventional asymmetric flow field flow fractionation (AF4) is useful in size-based separations of polymers, nanomaterials, and small particles in solution. When these are dissolved or suspended in solvents, an electric field can be generated between the solute and solvent. This is called the zeta potential. The zeta potential is fundamental in describing the behavior of the mixture. Adding an electric field to an AF4 cell provides an electrical selectivity to the size-based separation. Particle and molecule charge is important in protein aggregation, polymer flocculation, particle agglomeration, and pharmaceutical formulations.

This year, Wyatt Technologies and Postnova Analytics both introduced fractionation chambers enabling electric asymmetric field flow fractionation (EAF4). The Eclipse Mobility EAF4 from Wyatt is built around its EAF4 channel and features inert PET housing, platinized stainless-steel electrodes, and a special ceramic frit. The electrical connection to the channel works with a magnet guided “fly-on” plug. A unit combines a high-precision, programmable power supply plus two measuring cells for conductivity and pH. Data acquisition and processing are fully integrated in Wyatt’s Eclipse VISION software suite.

Postnova presented the EAF2000 electrical flow FFF series to complement its instruments for thermal and centrifugal models. The modular design facilitates adding a Malvern Zetasizer Nano for measurement of zeta potential of separated particles.

Since the concept of EAF4 is novel, let’s see how it works. Figure 1 shows a cross-section of an FFF flow cell. An electrical potential is introduced across the flow cell. Positively charged particles are repelled from the anode into the higher-velocity parabolic flow path. This separates them from the neutral or negatively charged particles.

Figure 1 – Schematic of flow cell for EAF4. With AF4, the particles move by diffusion away from the cell bottom. Different particles have different diffusion speeds. The smaller move quickly to the high-velocity profile and are swept to the detector first. Larger particles move more slowly and emerge from the cell later. With EAF4, electrodes are added on the top and bottom. When a dc potential is applied, charged particles are repelled from the iso-charge region and are attracted to the opposite charged side. This adds a charge selectivity to AF4. (Image courtesy of Postnova Analytics.)

A typical output is presented in Figure 2 for a sample of negatively charged polystyrene standards. When the voltage is off, one operates in the AF4 regime (blue Gaussian line) The radius of gyration measured by light scattering is the upward trending blue line. When the bottom plate is negatively charged, the anionic particles are repelled from the lower membrane and move by a combination of diffusion and electrical repulsion into the faster-moving flow profile. Hence, they emerge more quickly.

Figure 2 – Separation of 26-nm negatively charged polystyrene latex nanoparticles using the Postnova EAF2000 system. The blue fractogram marked with “0” has no electric field applied in the channel. The green fractogram marked with “-“ has a negative charge on the channel bottom; this results in repulsion between the channel bottom and the negatively charged particles, increasing the amount of time the particles spend in the faster flows, resulting in earlier elution. The opposite is true for the red fractogram marked with “+”; a positively charged channel bottom results in later elution for the negatively charged particles. (Image courtesy of Postnova Analytics.)

Sample preparation

EDGE

CEM is noted for microwave digestion technology that enhances sample prep by rapid heating. At Pittcon 2018, CEM introduced a novel and very rapid extraction system called the EDGE (energized, dispersive, guided extraction). President and CEO Mike Collins, Ph.D., notes that about 75% of the analysis time for a typical HPLC sample is in the preanalytics or sample prep stage. A weighed sample is placed in a tube above the bottom frit. A layer of dispersant (called Q-sorbents) such as silica is added on top of the sample. For extraction, the tube is placed in the EDGE. When the run starts, the displacing solution is rapidly heated and pumped in around and then upwards through the sample and dispersant bed—the entire process is complete in about 5 minutes. The liquid phase containing the target analytes is made to volume and is analyzed by GC or HPLC. The EDGE is optimized for around 12 samples, so labs with high sample loads can employ several systems.

Oasis PRiME MCX

Phospholipids qualify as ubiquitous interferences in many analytical protocols, especially those using electrospray ionization/MS (ESI/MS), where they cause ion suppression or loss of signal. Solid-phase extraction with Oasis PRiME MCX from Waters removes about 99% of phospholipids. The protocols for plates and tubes usually involve only 3–4 quick steps.

5910R desktop centrifuge

Eppendorf’s 5910R is a refrigerated desktop centrifuge that accommodates plates, mini-tubes, and vials. Despite its high maximum rotor speed, the instrument is quiet and vibration-free. A novel rotor plate fits tightly over the samples to greatly reduce aerosol, leading to sample-to-sample contamination.

Thin-layer chromatography

AMD 2

Camag introduced automated multiple development with the AMD 2. Multiple development in thin-layer chromatography (TLC) uses a series of repetitive development and dry cycles to focus the analyte spots. Manually, the process is tedious, but with AMD 2, it is a nonissue. The first development cycle is run in the normal manner with mixed solvent. Solvent demixing occurs as the first run proceeds. This produces a polarity gradient, where the analytes no longer move. After vacuum drying of the plate, the second development is initiated, but with a mixture of lower elution strength. This focuses the bands. After several dry and development cycles, each with lower elution strength, the bands are more tightly focused and can be read with a densitometer. Camag reports that 40 bands have been detected with an 80-mm separation distance.

Vapor deposition

Biocompatibility is a frequent concern in liquid chromatography, even with small molecules such as potential chelators. SilcoTek posted examples of silica coating metal columns using the patented Dursan vapor deposition process. The company claims that Dursan-coated columns and parts have 400–1600-nm-thick SiOx:CHy film. This can protect parts such as stainless steel, aluminum, and titanium from corrosion at temperatures below 80 °C. Proof examples include LC separation of tetracycline showing greatly reduced tailing. Reduced surface fouling such as biofilms is another application.

Gas-phase separations

Portable gas chromatographs designed for at-site analysis attracted attention, as they have for the last few decades. The vendors use microfluidic technology, where the gas flow is via channels etched into a chip of glass, silicon to reduce dimensions, fittings, and complexity. The general problem has been lack of durability and robustness.

Micromachined GCs

GC models L and M

Zebra Analytix was founded in 2017 to develop and market chip-scale gas GCs that require high speed or portability. The key was developed at Virginia Tech and licensed to Zebra. The chip-based design reduces size and complexity while enabling chromatographically efficient array of machined posts supporting the stationary phase.

The Zebra-GC model L is a basic low-cost miniature GC that relies on Bluetooth communications to a human interface such as a computer or smart phone. Columns are heated directly with the silicon chip, which has 100× higher thermal conductivity than silica. Detection is with either a thermal conductivity detector or microflame ionization detector. The Zebra-GC model M adds a preconcentration sample module and compatibility with multicolumn chips. The company touts its MEMS chip as an electronic nose.

ChromPix2

APIX Analytics won a Pittcon Award five years ago for a novel GC design using chip technology. This year, the company introduced the ChromPix2, an ultrafast GC enabled by its microchip technology. One chromatogram showed the separation of C1–C5 hydrocarbons in 22 seconds. The ChromPix2 can run up to four channels simultaneously, including individual carrier gases, columns, and samples.

Portable GC×GC

NovaTest P1000

Multidimensional separations make sense when one needs more chromatographic resolution. Nanova presented the NovaTest P1000, which uses microfluidic technology for the portable GC niche. The P1000 has interesting specifications: size—14 × 12 × 6 in.; weight—15 lb; first column 6 m, second column 2.4 m; column heater: 200 °C; carrier gas: He bottles; detection limit: 10 ppt for benzene in air; power: 24-V Li battery; sufficient for 8 hours of operation.

Laboratory GCs

Nexis GC-2030

Shimadzu Scientific Instruments introduced the Nexis GC-2030  for general applications. The attractive touch-panel human interface with intuitive icons provides status at a glance. Another sure-to-be-popular feature is that the column fittings can be tightened by hand, greatly simplifying changing columns.

Especially impressive is Shimadzu’s focus on the carrier gas. The 2030 features an “eco mode” for sustainability when helium is required. Plus, it reduces electricity when the instrument is idle. Hydrogen for the carrier gas provides the highest separation efficiency across a wide range of linear velocities. An optional built-in sensor monitors real-time levels of hydrogen in the oven. Should the sensor detect excessive hydrogen, it will trigger shut-off of the hydrogen flow. Chromatographers can choose from four inlets, six detectors, and specialized valve accessories. These are required by specific methods in petrochemical, environmental, food, and pharmaceutical analysis.

Ultrafast 500 GC

Ellutia’s 500 GC starts with direct electrical heating of the metal capillary column that supports a heating rate of 60–1000 °C/min. The columns are typically 2–1 m long with i.d.s in the range of 100–320 µm. Peaks are only 0.1–1.0 seconds at half-height. Run times are usually less than 5 minutes, and often much shorter. Currently, the only detector is flame ionization, but additional detector options are expected shortly, including electron capture, flame photometric, thermal energy analysis, and time-of-flight (TOF)/MS.

Detection of CO and CO2 with an FID

Jetanizer

Activated Research Inc. has the solution for those who want to convert a flame ionization detector (FID) to detect CO and CO2—the Jetanizer. This small unit, which fits inside the FID, catalytically converts CO2 and CO from the column to methane, which is easily detected by the FID over the concentration range of 100% down to ppb.

GC/MS

Pegasus GC-HRT+ and GC-HRT+ 4D

LECO introduced two large GC×GC instruments: Pegasus GC-HRT+ and GC-HRT+ 4D. Both incorporate Encoded Frequent Pushing (EFP) to extend the detection sensitivity and dynamic range of the TOF/MS by a decade. With EFP, the ion cloud is pulsed by the orthogonal accelerator many times per spectrum to increase duty cycle and counts. The 4D utilizes LECO’s thermal modulation system for GC×GC.

GC capillaries

MilliporeSigma has exclusive license to the ionic liquids for GC stationary phases developed by Prof. Dan Armstrong of the University of Texas at Arlington. New columns include the SLB-IL for chromatography of polar analytes, including phenols and alcohols. Tmax varies with film thickness, but can be as high as 280 °C.

The SLB-ILD3606 capillary column focuses on assays of aromatics and oxygenates in petroleum products per ASTM 3606. It is particularly suitable as a single column or first column for GC×GC applications. The stationary phase is a 0.2-µm ionic liquid film. Length is 30 or 60 m × 250 µm. Tmax is 260 °C.

The SLB-ILPAH is an ionic liquid stationary phase in wall-coated opentubular (WCOT) format. Dimensions are 20 m × 180 µm i.d. Tmax is 300 °C. Each column is tested to assure resolution of key polyaromatic hydrocarbons (PAHs), including phenanthrene/anthracene; benzo[a]anthracene/chrysene/triphenylene, and benzo[b]fluoranthene/benzo[k]fluoranthene/benzo[j]fluoranthene.

The SLB-PAHms offers low bleed for separation of polynuclear aromatics using MS detection. A variety of column lengths and film thicknesses are available. Tmax is 250 °C.

Water via GC

The moisture content of many materials is usually detected gravimetrically or with Karl Fischer protocols. Shimadzu used its gas chromatograph with unique Barrier Discharge Ionization detector (BID) to detect water eluting from a Supelco water column (Watercol 1910, MilliporeSigma). Detection limit with BID is less than parts-per-million. The GC method is recommended for assays when matrix components interfere with Karl Fischer determinations.

GC/MS and LC/MS

QDA

The advent of low-price, small, single-quadrupole MS instruments such as the QDA from Waters is changing the workflow in LC labs. UV detectors are being replaced as the general-purpose detector. In GC, the FID is giving way to the MS (either single-quad or TOF, even in manufacturing environments).

Occasionally, an unexpected result such as a new peak is noticed. Aviv Amirav of Aviv Analytical presented a poster describing TAMI software. Developed at Tel Aviv University, the software augments the usual library searches and isotope ratios with a postrun calibration to refine the mass accuracy. The protocol is simple: start with two peaks of known identity and accurate mass. Ideally, they bracket the unknown analyte in retention time. Use the accurate mass of the two brackets to calibrate the mass of the unknown peak. This will usually reduce the ambiguity of isobaric ions.

Molecular rotational resonance for reaction monitoring

Chiral MRR spectrometer

Molecular rotation spectroscopy is used in characterizing small molecules in interstellar space. Thus, I was intrigued with the Chiral MRR Spectrometer from BrightSpec, Inc. Molecular rotational resonance (MRR) is very useful in monitoring reactions with volatile compounds, since each molecule has a fully resolved and unique rotational spectrum, usually in the microwave region. Cited applications include analysis of diastereomers, conformers, and enantiomeric excess. The instrument scans the frequency range of 9–18 GHz. This covers the molecular weight range of 70–350 Da. Typical sample size is <1 mg; limit of detection is <1%. The major limitation is that molecules need to be in the gas phase. In the liquid phase, intermolecular interactions are so strong that the spectrum cannot be obtained.

Summary

Pittcon remains a compelling annual event for scientists involved in the analysis of chemicals, biochemicals, and therapeutics. Pittcon 2019 is scheduled to be held in Philadelphia, PA, March 17–21, 2019. For more information, visit www.pittcon.org.

Robert L. Stevenson, Ph.D., is Editor Emeritus, American Laboratory/Labcompare; e-mail: [email protected]