News. Academia. Real-time Weight Analysis for Healthier Babies. Analytical solutions in the laboratory. August 2014

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1 Academia Analytical solutions in the laboratory 15 News August 2014 Real-time Weight Analysis for Healthier Babies A 2013 medical study has shown that waiting for up to a minute after birth to cut the umbilical cord can improve a baby s health. One English hospital is now using continuous weighing and LabX software to determine the optimal time to cut the cord for maximum mother-baby nutrients transfer. According to the New York Times 1, a 2013 medical study has shown that delaying the severing of the umbilical cord by a minute or so after birth can help ensure sufficient nutrient transfer via blood and other fluids from mother to baby. Birth weights improve and the baby s hemoglobin and iron stores rise. The study also shows that these babies were less likely to be iron deficient 3-6 months after birth. However, waiting too long may increase some health risks. Therefore, one English hospital is now using real-time continuous weight readings to measure the flow of blood and other fluids into the newborn baby from the mother s placenta. The purpose is to define guidelines for reaching the optimal weight equilibrium prior to making the cut. Real-time results To obtain real-time data for their research, the hospital is using a METTLER TOLEDO XS8001L balance connected to LabXDirect software, which automates and manages data in a straightforward and secure manner. With a capacity of 8 kg and readability of 0.1 g, the balance has the accuracy required to measure the small amounts of fluid transfer and the weighing pan is large enough to assure the baby s safety during the weighing process. LabXDirect receives continuous weight readings from the balance and generates a real-time graph in Excel to help the attending physician know when to cut the cord. The LabXDirect-XS8001L combination allows sufficient data points

2 Laboratory Automation XS8001L precision balance connected to LabX Direct PC to be collected in order to decisively judge when fluid transfer has stopped and also takes into account anomalous readings caused by the baby s movements. The real-time graph is an essential visual aid in deciding when fluid transfer has stopped. LabX flexibility LabXDirect software can send data to any windows-based analytical program. The layout of the data is configurable according to application needs. Userdefined information can also be automatically added to the captured data to help with identification and the compilation of results. This is proving helpful, in the hospital s case, as it makes it a simple process to add further information concerning longer-term health outcomes and to continue to compare weight results over time. Better outcomes LabXDirect could prove a helpful tool in hospitals if the methodology catches on. The study is being performed on babies born full- and pre-term. If results bear out, this kind of real-time, continuous weighing immediately after delivery could help ensure that all babies, especially the smallest and most vulnerable premature ones, receive the highest possible nutrient transfer after birth to get the best possible start in life. Text: Julia Schenk Analytical Weighing Product Manager } 1: Study Finds Benefits in Delaying Severing of Umbilical Cord. Saint Louis C. The New York Times. July 10, Publisher Mettler-Toledo AG Laboratory Division Im Langacher CH-8606 Greifensee, Switzerland Production LAB Division Marketing Global MarCom Switzerland Subject to technical changes. Mettler-Toledo AG 08/14 Printed in Switzerland. 2 METTLER TOLEDO Academia News 15

3 Find the Failure with High-Speed Thermal Analysis The processing conditions of polymers influence morphology, which, in turn, affects their quality. The Flash DSC1 detects when processing conditions are the underlying cause of failure, thanks to heating and cooling rates of several 10,000 K/s. Certain process induced effects, such as the melting behavior of crystals formed in production, can only be studied with Differential Scanning Calorimetry (DSC) if reorganization processes are suppressed, i.e. during the first heating round. Until now there was no instrument able to suppress reorganization processes. METTLER TOLEDO s Flash DSC1, with heating and cooling scanning rates of over 10,000 K/s, finally makes this possible. Figure 1: Conventional DSC curves at 10 C/min of two polypropylene samples. Figure 2: Flash DSC curves at 1000 C/s with evaluated average peak temperatures. A striking comparison: DSC vs. Flash DSC Morphology characterization of two differently processed Polypropylene (PP) products by DSC is shown below. Both products have been processed under the same conditions except their cavity. In practical application, the samples labeled C1 and C4 demonstrate different impact resistances. Conventional DSC measurements at 10 C/min, shown in Figure 1, did not reveal any significant differences. Flash DSC measurements of the initial material at 1000 C/s are shown in Figure 2. Four samples of about 100 ng from several areas of the bulk sample were analyzed for eaach product in order to assess measurement reproducibility. The average peak temperature of sample C1 is about 7 K lower than that of C4. This indicates that the average crystal size in sample C1 is smaller than that in sample C4. This explains the different impact resistances of the two products. Text: Matthias Wagner Thermal Analysis Product Manager } Source: Influence of processing conditions on polymer crystallization measured by fast scanning DSC, J.E.K Schawe, Journal of Thermal Analysis and Calorimetry, /s , page 1-9 3Thermal Analysis METTLER TOLEDO Academia News 15

4 Low-volume Pipetting Accurate 96-well Pipetting for Early Identification of Diseases Researchers have recently developed a more accurate method of identifying certain Lysosomal Storage Diseases (LSDs) in newborns. The Liquidator 96 speeds up the sample preparation process and ensures high accuracy levels in the diagnosis of these genetic diseases at the earliest stage. Lysosomal storage diseases are a family of disorders with mild to severely debilitating symptoms. These diseases are usually caused by the mutation of proteins that are involved in lysosomal processing. The severity of symptoms depends on which proteins are mutated, how they are mutated, different factors controlling gene expression and environmental factors. There is often a delay in the diagnosis and treatment of LSDs due to their variable presentation and nonspecific symptoms. Diagnosing LSDs with tandem mass spectroscopy In The Journal of Pediatrics paper, Identification of Infants at Risk for Developing Fabry, Pompe or Mucopolysaccharidosis-I from Newborn Blood Spots by Tandem Mass Spectrometry, by Scott, et al, the authors developed a method that uses mass spectrometry to screen for many LSDs in parallel. They first took dried bloodspots from newborns, in which many lysosomal enzymes retain activity, and re-suspended them in a buffer containing the appropriate enzyme substrates for the enzymes whose defects cause the diseases. Using tandem mass spectrometry, the team could distinguish whether a given infant was deficient in any particular enzyme activity. Depending on the enzyme activity in a given bloodspot, the authors analyzed the gene sequences of the newborns to confirm whether low enzyme activity measured in the assay correlated with mutations in the same enzyme. Scott, et al, found that their method increased the likelihood for the detection of Fabry, Pompe and mucopolysaccharidosis-i over that of standard clinical diagnosis. Liquidator 96 the instrument of choice The experiments required the analysis of more than 100,000 bloodspots. Such a high number of samples required an accurate and systematic sample preparation process. Small punches of each bloodspot were placed in a 96-well plate. Using METTLER TOLEDO s Liquidator 96, the researchers were able to add enzymatic reaction solution, reaction 4 METTLER TOLEDO Academia News 15

5 Error reduction Liquidator 96 can be used to quickly and easily set up the most demanding applications, such as pipetting nucleic acid templates into reactions. Quality qpcr data is assured thanks to Liquidator s excellent reproducibility. Liquidator 96 for precise benchtop pipetting quench and product extraction solvents to the plate rapidly and accurately. These samples were then used for tandem mass spectrometry. The Liquidator 96 is a highly accurate and precise benchtop 96-well pipetting instrument that does not require any electricity for operation. With 96-channels pipetting at the same time, the Liquidator 96 can significantly accelerate experimental workflows beyond what is possible with single and multichannel pipettes. In time-critical applications, like enzymatic reactions, it is especially important that the reaction is started in all 96-wells at the same time. Liquidator carries out this task simply and accurately and avoids the risk of skipped rows, a common scenario with multichannel pipetting in 96-well plates. Text: Murray Anderson RAININ Marketing Head } Source: A Tandem Mass Spectrometry Triplex Assay for the Detection of Fabry, Pompe, and Mucopolysaccharidosis-I (Hurler) Clinical Chemistry 56: (2010) METTLER TOLEDO Academia News 15 5

6 Particle Tracking Visualize, Understand and Optimize Crystallization Processes To achieve an in-depth understanding of crystallization processes, scientists and engineers are investing into the next generation of in-situ vision and microscopy tools. These tools enable key, previously unobtainable, mechanisms to be identified, including crystal growth, secondary nucleation, seed aggregation and oiling out. Achieving greater process understanding enables scientists to make evidencebased decisions, anticipate scale-up issues and bring products to market faster and with higher quality standards. This process understanding is the basis for the successful and timely development of optimum crystallization processes. The implementation of probe-based technologies further enhances process understanding by providing real-time information and critical knowledge of crystal, particle and droplet behavior enabling scientists to see the crystallization as it happens in the reactor or pipeline. The in-situ nature of these technologies ensures the detection of process inconsistencies and improves product quality. In process real-time image microscope In-situ microscopy, PVM (Particle Vision and Measurement), offers a faster alternative to traditional offline visualization methods and provides a different perspective to scientists and engineers involved in the development, scaling-up or transfer of crystallization processes. PVM also eliminates time-consuming sampling and sample preparation as it captures data as it naturally exists in the process and detects process changes that could take months to discover with offline techniques. This enables scientists to immediately understand how particles respond to process conditions facilitating faster decisions concerning the next experiments to perform. Additionally, data that is simply unavailable via offline sampling is shown to identify transient or elusive crystallization mechanisms at the root of poor crystallization that impact crystal size and impurity profiles. PVM for enhanced process knowledge PVM allows evidence-based process decisions to be taken that help scientists and engineers deliver desired crystallization parameters in less time for faster product development. Batch failures are eliminated and more consistent filtration, drying and formulation in scale-up and production is achieved for valuable time and cost-savings. PVM Technology is a probe-based vision tool for immediate insight into crystal, particle and droplet size and shape. PVM enables chemists and engineers to detect and understand process changes that could take months to discover with traditional offline microscopy techniques. PVM uses a high-resolution CCD camera and an internal illumination source to obtain high quality images even in dark and concentrated suspensions or emulsions. With no calibration needed and easy data interpretation, PVM quickly provides critical knowledge of crystal, particle and droplet behavior. Text: Des O Grady AutoChem Market Development Manager } 6 METTLER TOLEDO Academia News 15

7 Particle Vision and Measurement (PVM) provides insight into particle size, shape and count. In combination with EasyMax synthesis workstation and ReactIR reaction monitoring system, a better reaction understanding is achieved as well as key scale-up information. METTLER TOLEDO Academia News 15 7

8 Know-How Don t Let Electrostatic Charges Influence Your Weighing Results One of the most common problems experienced when weighing dry substances in a laboratory environment is the influence of electrostatic charges, leading to inaccurate weighing results. The new XPE analytical balance offers a unique technology to detect electrostatic forces, measure its influence in the weighing and eliminate them. StaticDetect Built-in StaticDetect technology warns you when electrostatic charges affect the weighing results above your defined threshold. ErgoClip The ErgoClip basket for plastic and glass tubes shields the weighing pan from electrostatic changes. Small tubes also reduce the risk of creating charges. 8 METTLER TOLEDO Academia News 15

9 FAQ Electrostatic Charges in Weighing 1. What are electrostatic charges? An electrical charge on the balance or vessel to be weighed causes electrostatic forces. Electrostatic forces can alter weighing results either increasing or diminishing the real weighing value. 2. How are electrostatic charges originated? Friction is the most common way that electrostatic charges are generated. However, under climate controlled environments, such as the typical analytical lab, charges are more easily generated and lead to greater source of error. Weighing a small quantity of dry sample into a large glass or polymer vessel will also significantly increase the error of the weighing result. 3. How do they influence weighing results? Electrostatic charges exert forces on the sample to be weighed and the weighing pan, thus causing significant falsification of measurement results. Inaccurate weighing results range from few milligrams up to 100 mg. Antistatic Kit Attach the Antistatic kit to the analytical balance and eliminate charges without causing turbulences in the weighing chamber. Download the Electrostatic Charges in Weighing whitepaper METTLER TOLEDO Academia News 15 9

10 Product Highlight Pipet-Lite XLS+ Performance You Can Feel The recently launched Pipet-Lite XLS+ manual pipettes help researchers to achieve reproducible results with exceptional comfort. New elastomeric seals and polymer tip ejectors, along with the patented LTS LiteTouch System, deliver smooth pipette operation. The combination of the sure-fit handle, light springs and Magnetic Assist technology ensures smooth, light operation and significantly reduces the risk of repetitive strain injuries. 121 C GLP/GMP compliant Rainin pipettes were the first in the world to be equipped with Radio Frequency Identification (RFID) chips to store on-board service and data profiles, track calibration data and manage pipette inventory. All-around tip ejector XLS+ single channel pipettes have high-density polymer tip ejectors that are corrosion free and highly resistant to chemical and physical damage. The ejector slides off in a single, easy motion for cleaning. Autoclavable XLS+ pipettes are designed for easy autoclaving of the complete liquid end, including the seals. Easily removable, autoclaving XLS+ liquid ends won t compromise performance or feel METTLER TOLEDO Academia News 15

11 Calorimetry for Safe Processes from Screening to Production Uncovering potential safety issues or non-scalable conditions is essential to the safe development and scaling of process. EasyMax HFCal provides reaction safety information early in development while Opti- Max HFCal determines the heat and scalability details necessary for safely scaling processes. Both calorimetry workstations provide key information for enabling timely chemistry and process decisions to be made. Process development Characterize and optimize reaction conditions in a controlled, accurate and reproducible environment. Safety information is collected simultaneously saving time and resources. Understanding parameters Thermodynamic information, such as heat transfer, specific heat, heat flow or enthalpy is collected under both isothermal and non-isothermal conditions ensuring that process parameters are fully understood. Data analysis icontrol software automatically calculates and reports heat transfer data, specific heat of the reaction mass, heat flow and reaction enthalpies. METTLER TOLEDO Academia News 15 11

12 Broaden Your Lab Knowledge at Mettler-Toledo AG Laboratory Division Im Langacher CH-8606 Greifensee, Switzerland For more information Local contact: