Confidential - Company Proprietary Transforming Immunoassay Analysis: Unveiling the Power of the New Tuesday, May 28, 2024 | 5:30 – 6:30 PM | Beckman Coulter Vision Center, Dubai, UAE
It’s Time to Reimagine What’s Possible The status quo has no place here. Your busy lab needs next-level innovation to help you meet your growing demands. That’s why we developed an analyzer that goes beyond saving time — helping you create time to focus on what matters most.
The DxI 9000 Access Immunoassay Analyzer sets a new standard for today’s busy labs with meaningful innovations that create time for you to focus on what matters most. Amplify Your Impact Transform what’s possible with a system that does more for you — so you can do more for the people you serve. With the DxI 9000 analyzer, you can spend more time pursuing your purpose and elevating value for your healthcare ecosystem. Liberate You From the Laborious With greater insights in real time, the DxI 9000 analyzer maximizes uptime so you can meet accelerated demand with confidence. Power Your Performance Unleash the power of your laboratory. The DxI 9000 analyzer delivers meaningful innovations that take diagnostics to the next level. Through an integrated approach that brings people, instrumentation and precise results together, the DxI 9000 analyzer opens up new opportunities for value, growth, and innovation. MEET THE DxI 9000 ACCESS IMMUNOASSAY ANALYZER
Time It’s among our most precious and fleeting resources. For the clinician driving to a decision, it is urgent. For the patient awaiting answers, it is seemingly endless. For the laboratory staff under pressure, it is priceless. In clinics, hospitals and urgent care offices, every minute counts. That’s why we’ve designed an instrument that creates time for laboratory staff to focus on the critical work that only a human can perform — with a menu that addresses the most pressing needs. CARDIAC CARE Delivering the critical cardiac results that physicians need to quickly and accurately manage their patients’ conditions INFECTIOUS DISEASE Supporting infectious disease testing at scale to help control epidemics, breakouts and chronic endemic illnesses REPRODUCTIVE HEALTH Helping to build families through diagnostics and a deep understanding of reproductive biology IT’S ABOUT TIME MENU INCLUDES Anaemia Adrenal / Pituitary Bone Metabolism Cardiovascular Diabetes Infectious Diseases Prostate Health Reproductive Health Sepsis / Inflammation Thyroid Tumour Markers Time means something different to us all, but its value is universal. Create more of it to focus on what matters most with the DxI 9000 analyzer.
The DxI 9000 analyzer does more than improve your lab’s efficiency — it redefines what you can achieve. What Could You Accomplish with No Daily Maintenance? Set a new standard in productivity with ZeroDaily Maintenance. The DxI 9000 analyzer eliminates daily maintenance, amplifying productivity and outclassing the competition with less than 15 minutes of automated cleaning per week. What Could Earlier Error Detection Mean for Your Performance? Know more and do more in every moment with PrecisionVision Technology. This patented camera machine vision technology detects and notifies you of processing errors in real time, triggering course correction right away. How Could Guided Workflows Boost Your Team’s Confidence? Partnering with you every step of the way, the SimpleSolve Onboard Guide notifies you of problems and helps you confidently resolve system needs in-house. ENVISION THE POSSIBILITIES AND STEP INTO YOUR LAB’S FULL POTENTIAL
Next-level Output Surging test volumes? We’ve got you covered. The DxI 9000 analyzer’s industry-leading throughput (up to 450 tests per hour), optimized reagent consumption, and improved yields and traceability accelerate answers and amplify productivity. Faster Results Count on assured, accelerated answers. Our Lumi-Phos PRO substrate comes to full glow in under a minute and accelerates the time to first result by 5 minutes for every Access immunoassay assay. Preparation time is also reduced; operators simply remove the reagents from the refrigerator and load them directly onto the analyzer — no need for preparation or equilibration. Enjoy an Intuitive Interface Empower your team and tap into your lab’s full potential. The analyzer’s intuitive interface clearly instructs users of all skill levels on what to do and when — removing the guesswork from your workflow. The easy-to-use display illustrates system performance at a glance, walks users through operation, and supports quick onboarding and issue resolution. Optimized Workflow We’re reaching across our immunoassay, chemistry and automation portfolios to streamline processes and simplify testing across your network. • Standardized reference ranges reduce variation and provide high-quality results • Shared reagent packs, consumables and tube racks further streamline your workflow MEANINGFUL INNOVATIONS. POWERFUL RESULTS.
Onboard Aliquot Management Onboard, refrigerated aliquot storage frees you from tracking down and reloading sample tubes for reflex or repeat tests. Liquid, Ready-to-Use Reagents Simply remove the universal reagents from the refrigerator and load directly onto the analyzer — no need to thaw or remove caps/lids. Packets are automatically discarded once completed, saving you time. Enhanced Pipetting Dedicated sample precision pipettor uses disposable tips to deliver samples to all four reagent build stations — and can deliver as little as 2 uL of sample with ≤2% CV. LIBERATE YOU FROM THE LABORIOUS DxLAB Sample Racks With seven flexible positions, our DxLAB sample racks accommodate multiple tube types and sizes, as well as nesting cups. Disposable Tips Single-use tips deliver samples at the aliquot location and during reaction build to minimize carryover, accelerate operation, support precise sample delivery and ensure quality results. Service You Can Count On Increase confidence in your instrument availability with DxS IntelliServe. This secure, cloud-based, remote service and diagnostics solution provides real-time monitoring and predictive analytics to maximize your instrument’s availability and deliver patient results without interruption.
We’re Taking Automation to the Next Level Perpendicular Connection to Automation Provides easy access to three sides of the analyzer. Direct Track Sampling Transfers fluid from the sample tube carrier to the analyzer, allowing tubes to progress along the automation track without interruption. Intelligent Automation Moves each tube down the right path according to its urgency Since the DxI 9000 analyzer offers onboard sample aliquot storage for all necessary testing, tubes stop only once for a single aspiration. Clinical Informatics enables autoverification and reflex rules to automatically run tests from aliquot storage, eliminating manual intervention and handling to create time. When your lab runs this efficiently, the opportunities to extend value throughout your organization are virtually limitless. From improving patient care to reducing wait times to boosting satisfaction, you can leverage the time you create to make an impact where it matters most. AUTOMATION THAT EMPOWERS
Keeping You One Step Ahead Your world is ever changing. Be ready for it with the DxI 9000 analyzer. More than an instrument, it is a partner to support your evolving needs and priorities — today and into the future. With a regular cadence of software updates being planned and shared, it keeps you current on the latest features and data security.
© 2022 Beckman Coulter, Inc. All rights reserved. Beckman Coulter, the stylized logo, and the Beckman Coulter product and service marks mentioned herein are trademarks or registered trademarks of Beckman Coulter, Inc. in the United States and other countries. Lumigen and the Lumigen product marks mentioned herein are trademarks or registered trademarks of Lumigen, Inc. in the United States and other countries. Lumigen is a Beckman Coulter company. BR-123456 | 2023-11153 Reimagine what’s possible and step into your lab’s full potential. With the DxI 9000 Access Immunoassay Analyzer, it’s about time. Create time to focus on what matters most. Start today at BeckmanCoulter.com/DxI9000 Picture the Possibilities Scan here to feel the power of the DxI 9000 analyzer in your own lab with augmented reality.
Main Specifications Analytical method • Chemiluminescent detector: luminometer Barcoded reagents • Automatic tracking of: - Number of tests - Available tests - Expiration date - Lot number - Calibration expiration and printouts Calibration • Calibration curve stability up to 64 days (assay dependent) • Calibration curves and parameters displayed on screen Communication modes • Unidirectional, bi-directional, bi-directional with true host query • Both RS-232 and LAN connections are supported Compartment temperatures • Incubator and wash/read wheel: 98.6°F (37°C) • Sample wheel: 39.2°F to 50°F (4.5°C to 14°C) • Reagent compartment: 39.2°F to 50°F (4.5°C to 14°C) Immunoassay menu capacity • >50 preprogrammed, barcoded immunoassay methods currently available Measurement principles • Acrydinium based chemiluminescent Lumi-Phos PRO Sample container sizes • Ability to accommodate any tube between 12–16mm in diameter and 75–100mm in height • Sample cups: - 0.5 mL - 2.0 mL - 3.0 mL • 2.0 mL insert cups • Pediatric insert • Auto aliquot tube Sample management/capacity • 140 sample tubes (20 racks of 7 tubes), unique continuous loading feature • Primary tube released after aliquot is made (approx. 1 minute) 300 aliquots (≤200 μL) per hour • Capable of automation connection • Barcode symbology: - Ability to read 1-D and 2-D symbologies with camera technology. • Sample volume: - 2–250 µL (assay dependent) - 500 µL in aliquot vessel, maximum (including any potential reflex tests) • Sample and reagent pipettor obstruction detection Sample types (assay dependent, partial list) • Serum • Plasma • Urine • Amniotic fluid • Whole blood Create time to focus on what matters most. The DxI 9000 Access Immunoassay Analyzer sets a new standard for today’s busy labs. With meaningful innovations that amplify your impact, liberate you from the laborious, and power your performance across your health system, we’re taking diagnostics to the next level. Review these instrument specifications to set your lab up for success. Instrument Specifications
© 2024 Beckman Coulter, Inc. All rights reserved. Beckman Coulter, the stylized logo, and the Beckman Coulter product and service marks mentioned herein are trademarks or registered trademarks of Beckman Coulter, Inc. in the United States and other countries. Lumigen and the Lumigen product marks mentioned herein are trademarks or registered trademarks of Lumigen, Inc. in the United States and other countries. Lumigen is a Beckman Coulter company. All other trademarks are the property of their respective owners. Pending clearance by the United States Food and Drug Administration; not yet available for in vitro diagnostics use in the US. For Beckman Coulter’s worldwide office locations and phone numbers, please visit www.beckmancoulter.com/contact DS-41900 | 2022-10755 Installation Requirements Dimensions and weight • Analyzer: - Weight: 1,842 lbs (836 kg) - Length: 79 in (200 cm) - Height: 63 in (159 cm) - Depth: 41 in (104 cm) • Clearance Requirements: - Clearance around the analyzer for ventilation - Rear: Minimum of 20 in (50 cm) • Clearance around the analyzer for service - Rear: Minimum of 20 in (50 cm) - Left: 0 in (0 cm) - Right: Minimum of 15 in (38.1 cm) - Top: Minimum of 22 in (56 cm) - Front: Minimum of 40.5 in (103 cm) Waste requirements • Solid waste (Tips, RVs, Reagent Packs) collected in waste container. (No manual removal required for operation) • Tip trays, substrate bottles and caps stored separately for recycling capability purposes • Floor drain only • Drain Location: - Maximum distance 33 ft (10 m) from the system - Maximum height 4 ft (1.5 m) from the floor Power and environmental requirements • Power Supply: 200-240 VAC at 1600 VA, at either 50 Hz or 60 Hz, single phase • Frequency: 47–63 Hz • Power: No greater than 2,700 W • Computer: - CPU Intel Core i7-6700 processor - Memory: 2 x 16GB DDR4-2133 - Storage: 2 x 240GB SSD - Operating system: Windows 10 - External communication types: RS232 serial interface - Ethernet: LAN using TCP/IP • Monitor: - Touchscreen display: 21.5 in diagonal TFT LCD with projected capacitive touch • Interface: - Pixels: 1920 x 1080 RGB • Heat output: 4,231 BTU/hr • Ambient operating environment: • Ambient temperature: 64°F to 86°F (18°C to 30°C) • Humidity: 20% to 80% • Altitude: 7,500 ft (2.286 km) • Noise Level: <60 dB at 1000Hz • Water: No water requirement • Drain Volume: >1.85 gal/hr (>7 L/hr) Main Specifications continued Reagent storage capacity • 50 reagent packs - System menu can be configured to match laboratory testing patterns (ability to load one pack of 50 different assays or 50 packs of one assay) • Automatic disposal of empty packs Throughput • Up to 450 tests/hr maximum (one-step assays) Instrument Specifications Create time to focus on what matters most. Contact your local Beckman Coulter representative with questions, or keep learning at BeckmanCoulter.com/DxI9000
UNIQUE APPLICATION OF MACHINE VISION IN FUTURE AUTOMATED IMMUNOASSAY SYSTEMS Amit Sawhney, Marie Willette, Nicole Sovde, Favio Arita, Taka Mizutani Beckman Coulter, Inc., Chaska, MN USA BACKGROUND Conventional automated clinical diagnostic testing systems have various process monitoring functions (e.g. optical sensors, pressure sensors, thermistors, etc). These monitors check the integrity of instrument function, but most of those tools are limited to indirect sensing and do not directly monitor the critical elements of correct assay processing. This study examines the use of a new tool, machine vision, to directly monitor critical assay processing steps. The purpose of this poster is to describe the methods and results of the following machine vision applications: 1. Sample volume monitoring: image and software algorithms measure the distance from bottom of tip to sample meniscus, using pixels, then convert measurement to volume 2. Total reaction volume monitoring: image and software algorithms measure the distance from bottom of vessel to reaction meniscus, using pixels, then convert measurement to volume 3. Particle retention monitoring: image and software algorithms execute measurement of gray-scale gradient and convert to particle concentration 4. Residual volume monitoring: image and software algorithms execute pattern matching and convert to residual volume SAMPLE VOLUME MONITORING RESULTS Summary of accuracy and capability of the four applications: 1. Sample volume detection range was demonstrated to be 2 to 100 µL with ± 10% accuracy capability 2. Reaction volume detection range was demonstrated to be 50 to 250 µL with ± 10% accuracy capability 3. Residual volume detection was demonstrated with a minimum volume of 15 µL capability 4. Particle retention range of 40-100% retention was demonstrated with ± 5% accuracy capability This study confirms the performance of machine vision for direct measurement of various sample reaction volumes. Proactive and direct assessment will potentially permit future immunoassay systems to notify users of processing errors, permitting earlier detection and resolution, and lowering risk that erroneous but believable results will be reported. © 2019 Beckman Coulter. All rights reserved. Beckman Coulter, the stylized logo, and the Beckman Coulter product and service marks mentioned herein are trademarks or registered trademarks of Beckman Coulter, Inc. in the United States and other countries. CONCLUSION . SAMPLE VOLUME MONITORING METHODS PARTICLE RETENTION MONITORING METHODS RESDUAL VOLUME MONITORING METHODS RESIDUAL VOLUME MONITORING RESULTS PARTICLE RETENTION MONITORING RESULTS • Linear correlation plot across 4 instruments at different volumes (n = 24; 6 reps per volume) for non dilution and dilutions Before Aspiration After Aspiration After Dispense Purpose: • Camera at precise pipettor is used to detect tip presence/absence through all positions of the instrument and measure sample volume aspirated and dispensed • Camera can tell software to flag samples out of volume specification (kinks in tubing, pump/valve failures, tip alignment) or if tip presence/absence is in an incorrect state (fail to discard tip, fail to pick up, drops) Technology Used: Experimental Methods: 1. Camera was calibrated on three instruments to convert pixel to µL. Spectrophotometer as measurement comparison was calibrated for 2 – 105 µL delivery with dilutions of Orange G solution. 2. Instruments were programmed to aspirate and dispense Orange G solution at 2 – 105 µL delivery. 3. After each aspiration and dispense, images were taken by the camera and vessels were transferred to area for collection 4. Upon collection, vessel concentration was measured on spectrophotometer • Monochrome Camera - 1280x960, 130in CMOS, 40 FPS with a 6.2mm lens • Reflective Tape Background TOTAL REACTION VOLUME MONITORING METHODS TOTAL REACTION VOLUME MONITORING RESULTS Linear correlation plot of camera volume vs weighed volume 50 – 250 µL (n=20 per volume) Purpose: • Camera at Wash Wheel is used to measure substrate dispense volume before incubation and also assist with service and manufacturing for volume checks of pumps on the instrument • If substrate volume is too low, test can report too low. Volume delivery of reagent and wash pumps out of specification (kinked tubing, pump/valve failure, obstruction) can also impact test results Technology Used: Experimental Methods: 1. Camera was calibrated on three instruments to convert pixel to µL 2. Instruments were programmed to deliver 50 – 250 µL of Wash Buffer II solution and loaded with pre-weighed vessels 3. After each dispense and mix, images were taken by the camera and vessels were transferred to area for collection 4. Upon collection, vessel weight after dispense was measured 5. Actual volume ((post-fluid weight – pre-fluid weight)/density) was determined after measurements • Monochrome Camera - 1280x960, 130in CMOS, 40 FPS with a 6.2mm lens • Red Backlight 50 µL dispense 200 µL dispense Purpose: • Camera at Wash Wheel is used to measure particle presence/absence and can be used as a service test to measure concentration. • Particle concentration is a function of both pack fill and instrument (damaged magnetization, too much aspiration, misalignment) Technology Used: • Same camera and setup as used in Reaction Volume Monitoring Experimental Methods: 1. The camera was calibrated by measuring known concentrations 0.1 mg/mL particles ranging from 0 – 250% to establish a histogram curve. Spectrophotometer as measurement comparison was also calibrated to the same concentrations. 2. Instrument was programmed to deliver known amount of fluid for 30 – 150% concentrated packs. 3. After each dispense and mix, images were taken by the camera and vessels were transferred to area for collection 4. Upon collection, vessel concentration was measured on spectrophotometer 0% 20% 50% 100% • The bivariate fit between camera predicted %Conc and spectrophotometer predicted %Conc is linear with a strong correlation • The mean variance across the range is 2.2 %CV for the camera and 1.5%CV for the spectrophotometer. Normal Residual Volume >15 µL Residual Volume Purpose: • Camera at Wash Wheel is used to measure residual volume left in vessel after reaction build, wash of particles, and aspiration of excess fluid • If residual volume is too high (aspiration probe misalignment, obstructed tubing, vacuum failure), tests can report too low Technology Used: • Same camera and setup as used in Reaction Volume Monitoring Experimental Methods: 1. Instruments were programmed to inducing an aspiration failure mode by misalignment of aspiration probes at different heights and loaded with pre-weighted vessels 2. At each aspiration height, images were taken by the camera and vessels were transferred to area for collection 3. Upon collection, vessel weight after dispense was measured 4. Actual volume ((post-fluid weight – pre-fluid weight)/density) was determined after measurements • This study showed that at greater than 15 µL, the camera was able to correctly determine too high volume with 95% accuracy. PROBLEM STATMENT Load Samples Aspirate Sample Add Reagents Incubate Wash (separate Bound/Free) Read Report out • When we see erroneous results, the system doesn’t really provide information on each process inside instrument (= black box) Camera Backlight Camera Reflective Tape Pipettor
B-230: ADVANCED INSTRUMENT-GUIDED TROUBLESHOOTING FOR FUTURE AUTOMATED ANALYZERS Carl Erickson, David Heiden, Dan Henjum, Lynn Lord, Madhan Rajendran Beckman Coulter, Inc., Chaska, MN, USA BACKGROUND Current troubleshooting and maintenance methods for automated clinical analyzers are challenging and often require skilled operators to execute them. This can lead to additional system downtime, decreased laboratory throughput, and excessive use of a technologist's time. A consistent and simplified Help Wizard solution has been created on a prototype* to allow operators to complete these tasks more efficiently on future automated clinical analyzers. Instrument features, such as hardware sensors, are used to identify analyzer status. For example, during a barcode read failure, the barcode scanner can be polled to determine whether the failure resides with the consumable, or the analyzer. Then, the hardware and software interact to either automatically complete a workflow step, or present relevant Help instructions needed by the operator to manually complete an action. Software is structured to provide a consistent user interface experience for the performance of all Wizards. Workflows are interactive and allow for branching depending on system status or user input Wizards for Automated Analyzers The first step in creating these wizards, was to create a common framework and build infrastructure for dynamic communication between instrument subsystems, the instrument instructions for use, and the operator. These instrument-guided workflows, are initiated by the operator, but prompted by the analyzer. They direct operators of any skill level through the performance of procedures in a highly structured and consistent way using workflows that are segmented into steps that are performed jointly by the analyzer and the operator. Wizards are especially useful for highly regimented and complex activities such as troubleshooting, maintenance, or for rare tasks requiring human intervention. CONCLUSION While it is preferable to fully automate all maintenance, error handling, and troubleshooting processes, tasks remain that require human interaction, input, and judgement. The new advanced instrument-guided troubleshooting workflows improve the customer experience by: 1. Improving uptime by providing troubleshooting instructions more efficiently 2. Reducing the need for advanced training 3. Eliminating the need for printed troubleshooting information and tribal knowledge © 2020 Beckman Coulter. All rights reserved. Beckman Coulter, the stylized logo, and the Beckman Coulter product and service marks mentioned herein are trademarks or registered trademarks of Beckman Coulter, Inc. in the United States and other countries. All other trademarks are the property of their respective owners. RESULTS A METHOD A Figure 1 An example of an automated troubleshooting Wizard that consists of four steps. The current step in each frame is highlighted in blue on the left, and the accompanying instructions for that step is visible on the right. Use of Analyzer Hardware Analyzer hardware and sensors are used to enhance troubleshooting within the wizard to quickly identify root causes. Hardware has also been used to automate transitions between steps. METHODS C Integration with the Instructions for Use (IFU) The instructions contained in the wizards are created in conjunction with the content of the IFU to ensure all operator instructions are consistent across multiple formats (printed and electronic versions of the IFU, videos, analyzer System Help, online System Help, and wizard instructions). This also ensures that all operator instructions follow the same process for editing, review, approval, and translation. METHODS B RESULTS B Figure 2 Example of wizard instructions using text. Figure 3 Example of wizard instructions using video. PROBLEM STATEMENT To perform troubleshooting and maintenance procedures on many current automated analyzers, operators are often required to do the following: • Reference printed maintenance procedures • Follow complex troubleshooting guides • Rely on tribal knowledge • Perform complex manual tasks • Assume that they completed the task correctly • Manually navigate or perform diagnostic routines to return instruments to service • Stop all other work to focus on and complete the task Figure 5 Example of a wizard step displaying the actual image as seen by the bar code reader. Figure 8 Examples of a wizard used for routine maintenance. Wizards can run automated diagnostic and maintenance routines, such as priming or cleaning (left). When maintenance is completed through a wizard, the task completion is automatically recorded in the maintenance log (right). RESULTS C Figure 4 Example of a wizard step displaying the actual temperature data of the pertinent subsystem temperature probes, as well as the upper and lower range limits. Figure 6 Example of a wizard step confirming a cover has not been closed. Figure 7 Example of a wizard step providing an in-workflow input location for sample rack information. References: DxI 9000 Access Immunoassay Analyzer Instructions For Use, IUO (PN C31970 AC) Disclaimer: *The prototype is not cleared or approved for commercial use is any geography.
A method comparison study was performed to evaluate the prototype’s accuracy when compared to the predicate platform, Access 2, for PCT, hsTnI and TSH. Assay-specific controls and sample types were evaluated and analyzed using a Passing-Bablok regression. All three assays yielded passing method comparison results with slopes meeting the required specification of 1.00 ±0.1. As advances in automated immunoassay testing have allowed for improved sensitivity, specificity and shortened time to first result of diagnostic assays, expectations have also become more discerning. With product improvements, workforce shortages and consolidations, many diagnostic laboratories are adopting increased automation with higher throughput testing, while maintaining or improving their quality. Beckman Coulter is developing a new immunoassay system to address these needs while transferring the assay menu currently available on its Access 2 Immunoassay System. The new prototype system employs improved precision pipetting and an enhanced chemiluminescent substrate that allows for increased tests per reagent pack, increased sensitivity, improved precision, and shortened time to first result A comprehensive assay menu was characterized on the prototype analyzer and all data is compared to Access 2 performance. The three assays represented were selected based upon their clinical importance and frequency of use. Procalcitonin (PCT) is used as an early indicator of sepsis and/or sepsis risk and troponin (hsTnI) aids in the diagnosis of myocardial infarction ; both are used in critical care settings. Thyroid stimulating hormone (TSH) is used to assess thyroid status and has applications for both screening and monitoring in individuals with hyper- or hypothyroidism, as well as other thyroid disorders. For each assay, a panel of residual samples spanning assay analytical measuring ranges and commercially available quality controls were tested across three reagent lots, two calibrator lots, over multiple days of testing on three prototype analyzers and three Access 2 systems. Accuracy1, imprecision2, and sensitivity3 were calculated and compared to the Access 2 following procedures based on CLSI guidelines. PCT and TSH were evaluated and compared the increased tests per pack on the prototype to the standard tests per pack on the Access 2. B-012 Preliminary Performance of Access hsTnI, PCT, and TSH 3rd IS Assays on a Next-generation Prototype Analyzer† Kailey Soller1, Anne Young1, Sarah Thornburgh1, Ian Levine1, Mike Kjome1, Ronna Moore1, Matthew Posnansky1, Mark Habeck1, Nicole Malikowski-Hoffarth1, Chris Gruenhagen1, Kelsey Walt1, Mark Holland1, Corey Carlson1 1Beckman Coulter Inc., Chaska, MN Beckman Coulter’s next-generation, high- volume immunoassay analyzer is currently under development. The analyzer is designed to achieve a higher throughput, employ an enhanced chemiluminescent substrate (LUMI-PHOS PRO), deliver shorter turnaround times, increase tests run per reagent pack, and provide high- quality patient results with improved user workflows when compared to the legacy Access UniCel DxI 800 Immunoassay System. Assay data generated on the prototype analyzer demonstrates a strong correlation and similar imprecision to Beckman’s predicate platform, the Access 2 Immunoassay System (A2). Highlighted here are three example assays from the current portfolio, thyroid stimulating hormone (TSH), troponin (hsTnI), and procalcitonin (PCT), demonstrating improvements in sensitivity and precision achieved by the prototype analyzer. INTRODUCTION & METHODS A subset of preliminary data for the Access TSH 3rd IS, Access hsTnI, and Access PCT assays generated on the prototype analyzer is presented here. Each of these assays exhibit a strong correlation to Access 2, similar imprecision, and improved sensitivity as measured by limit of quantitation (LoQ). In addition to achieving quality results, an increase in number of tests per reagent pack is realized for both TSH and PCT assays. All data within this poster was generated by Beckman Coulter Diagnostics4. † The prototype is not cleared or approved for commercial use is any geography Preliminary assay data generated on the next-generation, high-volume immunoassay analyzer prototype system demonstrates a strong correlation to Access 2 and enhanced performance with regards to precision. Accuracy analyses showed there is minimal (<5%) dose difference between the prototype and predicate platforms. Additionally, characterization data demonstrates the opportunity to achieve improved sensitivity for assays including Access TSH 3rd IS, Access hsTnI, and Access PCT while increasing tests available from each individual pack for TSH and PCT assays. References 1. CLSI. Approved Guideline – Measurement Procedure Comparison and Bias Estimation Using Patient Samples, EP9C-ED3. Clinical and Laboratory Standards Institute. 2. CLSI. Approved Guideline – Evaluation of Precision of Quantitative Measurement Procedures, EP5-A3. 2014. Clinical and Laboratory Standards Institute. 3. CLSI. Approved Guideline – Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures, EP17-A2. 2012. Clinical and Laboratory Standards Institute. 4. Soller, et al. (2018-2020). Prototype analyzer evaluation [Unpublished raw data]. Beckman Coulter. © 2020 Beckman Coulter. All rights reserved. Beckman Coulter, the stylized logo, and the Beckman Coulter product and service marks mentioned herein are trademarks or registered trademarks of Beckman Coulter, Inc. in the United States and other countries. All other trademarks are the property of their respective owners. RESULTS - ACCURACY CONCLUSION Abstract RESULTS - PRECISION RESULTS - SENSITIVITY A three-day precision study was completed on three prototype analyzers and three Access 2 analyzers. Samples included commercially available quality controls and residual samples and were distributed across the assay’s measuring range. Estimates of total imprecision presented herein are inclusive of variability attributed to within-run, between-day, instrument-toinstrument, calibration-to-calibration, reagent lot-to-lot, and calibrator lot-to-lot. Quality control materials used were assay specific with PCT, hsTnI and TSH (3rd IS) using Bio-Rad Lyphochek Specialty, MORE Diagnostics’ Cardiac Markers and Bio-Rad Lyphochek Immunoassay Plus, respectively. Control concentration results on the Access 2 and prototype were compared to acceptable concentration ranges as determined by the manufacturer. PCT hsTnI TSH (3rd IS) Concentration (µIU/mL) SD %CV Concentration (ng/mL) SD %CV Concentration (pg/mL) SD %CV Access 2 Prototype† Access 2 Prototype† Access 2 Prototype† Access 2 Prototype† Access 2 Prototype† Access 2 Prototype† Access 2 Prototype† Access 2 Prototype† Access 2 Prototype† Low Sample 0.03 0.03 0.003 0.002 13% 6% 5.69 5.31 0.646 0.495 11.4% 9.3% 0.02 0.02 0.003 0.001 14.7% 4.5% Assay-Specific Controls Levels 1‐3 0.61 0.69 0.030 0.034 5.0% 4.9% 48.8 52.8 2.17 1.47 4.5% 2.8% 0.67 0.71 0.039 0.026 5.9% 3.7% 2.24 2.42 0.111 0.099 4.9% 4.1% 1242 1280 50.54 51.64 4.1% 4.0% 5.88 5.74 0.369 0.245 6.3% 4.3% 21.6 23.6 0.747 0.683 3.5% 2.9% 16779 16582 805.4 664.9 4.8% 4.0% 29.49 30.72 1.70 1.54 5.8% 5.0% Total Imprecision 6.4% 4.3% 8.3% 6.8% 6.6% 6.1% Samples were tested across each assay’s measuring range and sensitivity capabilities of LoB, LoD and LoQ were calculated for the prototype and predicate platforms. The calculated conservative surrogate estimates are shown below. Testing was completed across multiple pack lots and calibrator lots to also evaluate lot-to-lot variation. Limit of Blank (LoB) Limit of Detection (LoD) Limit of Quantitation (LoQ) RESULTS SUMMARY Figure 1a. Passing-Bablok analysis of PCT platform method comparison Figure 1b. Passing-Bablok analysis of hsTnI platform method comparison Figure 1c. Passing-Bablok analysis of TSH platform method comparison Accuracy (Passing‐Bablok slope) Access 2 vs Prototype Analyzer† PCT 1.025 hsTnI 1.001 TSH (3rd IS) 1.014 PCT (ng/mL) hsTnI (pg/mL) TSH (3rd IS) (µIU/mL) Claim ≤ 0.005 ≤ 4.0 ≤ 0.005 Access 2 0.002 1.23 < 0.001 Prototype† < 0.001 0.52 < 0.001 PCT (ng/mL) hsTnI (pg/mL) TSH (3rd IS) (µIU/mL) Claim ≤ 0.01 ≤ 4.0 ≤ 0.005 Access 2 0.004 1.56 0.003 Prototype† 0.002 0.63 0.001 PCT (ng/mL) 20% CV hsTnI (pg/mL) TSH (3rd IS) (µIU/mL) 20% CV Claim ≤ 0.02 ≤ 11.5 (10% CV) ≤ 5.0 (20%CV) ≤ 0.01 Access 2 0.007 2.9 (10% CV) 1.1 (20% CV) 0.004 Prototype† 0.003 0.75 (10% CV) 0.33 (20% CV) 0.001
The experimental subsystem with dispo-tip + pipettor mixing successfully improved sample delivery precision across dispensing range. Several different sample types were studied as well as different levels of viscosity. The results below suggested that there was very little impact from sample type changes. * Human Serum / Plasma Viscosity: 1.7 ~ 2.0 IMPROVEMENTS IN PRECISION OF LOW-VOLUME PIPETTING ON AN AUTOMATED ANALYZER Hitoshi Narita1, Kazuki Umebara1, Taka Mizutani2 1Beckman Coulter K.K., Mishima, Japan, 2Beckman Coulter Inc., Chaska, MN, USA © 2019 Beckman Coulter. All rights reserved. Beckman Coulter, the stylized logo, and the Beckman Coulter product and service marks mentioned herein are trademarks or registered trademarks of Beckman Coulter, Inc. in the United States and other countries. INTRODUCTION PIPETTOR DESIGN DILUTION PROCESS Precise and accurate delivery of patient sample is a critical step in obtaining accurate test results. Automated analyzers have improved precision over the years, but there is still opportunity to improve further. Additionally, there is a desire to conserve sample collected from patients, leading to a need for even smaller volume sample delivery. This team set out to develop motion profiles that would achieve very high precision (<1% CV) for small volume delivery and maintain fast throughput while eliminating sample carryover by employing disposable pipette tips. BACKGROUND Building a high throughput immunoassay analyzer that is very fast and without sample carryover is a challenge. One solution is to employ disposable pipette tips (dispo-tip). Avoiding sample carryover is important for all immunoassays. Problem Statement The UniCel DxI 800 was introduced in 2003 as the highest throughput immunoassay analyzer. Over the years the focus has shifted from speed to continuous improvement of assay performance, especially with the introduction of high-sensitvity assays. To that end, one key element of assay performance is sample delivery precision. The current specification of CV <2.5% for 10 µL delivery is adequate, but the capability of using smaller delivery volumes is desired for future development. Goals The team’s aim was to focus on four key performance areas with a new pipetting subsystem: 1. Fast Cycle time (throughput > UniCel DxI 800) 2. Accurate, small sample delivery volumes (</= 2 μL） 3. Sample delivery precision of < 5% CV at 2 uL delivery 4. Absence of sample carryover (dispo-tips) The experimental subsystem has demonstrated performance with dispo-tip as listed below • CV <1.5% for 2~5 µL • CV <1.0% for 5~250 µL • 1.0~4.0 mPaꞏs • 10~200x dilution rate There are several key elements to achieve high performance for the pipetting system using the dispo-tips. • Miniaturized Components to move together over multiple locations • Pipettor Mixing to wash out residuals inside dispo-tip • Number of Pipettor Mixing to mix sample + reagent to be uniform before aliquoting Having these key functionalities, the experimental subsystem would support improved assay performance when employed on an immunoassay analyzer. CONCLUSION PROTOCOL & MATERIALS ACRONYMS & DEFINITIONS SV – Sample vessel DV – Dilution vessel RV – Reaction vessel Dispo-tip – Disposable tips WB – UniCel Wash Buffer II RLU – Relative light units Paꞏs – SI unit for Viscosity RESULT （DILUTION) RESULT （NON-DILUTION) PIPETTOR MIXING PROCESSグラフ、チャートTest process A colorimetric method for determining precision was employed. An orange-colored dye (OG) solution containing a known volume of 7% bovine serum albumin solution was introduced to the system via a sample cup. The new pipettor was programmed to deliver varying volumes into a reaction vessel (RV). Concentration of the dye was calculated, and measurements of the delivery were performed using a spectrophotometer. Three different motion profiles were created for varying ranges of volume delivery (250 µL, 25-100 µL and 2-24 µL targets). All tests, with 6 different target values at both high and low viscosity, were conducted with 10 replicates per sample, using an 8 second pipetting cycle, on 5 different pipetting subsystems. Colorimetric method Dye ingredient : Orange-G (C16H10N2NaO7S2) Instrument Spectrophotometer : Hitachi U-3900H Auto dispenser : Hamilton microLAB MS615-DS Prototype for Sample Pipetting DxI with AU pumps for Reagent pipetting Protocol Program instrument to dispense 2, 5, 10, 25, 50, 100 or 250 μL of OG into RV (O.D.50 for <25 μL, O.D.25 for ≥ 50 μL) Fill WB to get total 500 μL for Spec measurement Run 10 Reps, 3 Runs for each OG volume condition Precision profile summaries by target value Although the results indicated increasing imprecision with high dilution rates, the highest dilution rate, 200x, still showed CV <2% from the additional pipettor mixing process. Precision profile summaries by target value on Dilution Process 250 µL 100 µL 50 µL 25 µL 10 µL 5 µL 2 µL Mixing times Unique Rinsing Motion A sample is dispensed into a reaction vessel followed by a rinsing motion where a pipettor syringe pushes and pulls sample + reagent together repeatedly to achieve good precision for low volume delivery. This enables washing out residual inside of dispo-tip to get high accuracy sample delivery. Push & Pull 3 way valvePressure Sensor ＳOpen to Air Mini Syringe Dispo-tip Sample Pipettor Design Details There are several locations to aspirate and deliver patient samples. The key to maintaining good precision with high throughput is to make all pipetting elements packaged and move them over multiple locations together. The left picture is showing the sample pipettor module together with the piping diagram below. Piping Diagram Dilution Process For the purpose of very low sample volume delivery <2µL, an extra process is provided to ensure the 10-200 times dilution is performed before being dispensed into RV. Timing Chart In order to maintain good precision with high dilution factor, a number of pipettor mixing steps was increased taking 2x 8sec per cycle, shown as below. Non-dilution (8 sec cycle = 450 tests/hr process speed) Dilution DV RV Dispo-tip RV Dispo-tip Mini Syringe3 way valvePressure Sensor Mandrel Collision Sensor This product is in development and is not available for sale. Pending achievement of CE compliance; not yet available for in vitro diagnostic use. Pending clearance by the United States Food and Drug Administration; not yet available for in vitro diagnostic use in the US. For Investigational Use Only.
A NEW AND IMPROVED CHEMILUMINESCENT SUBSTRATE (Mark Sandison 1 , Renuka De Silva 1 , Gamachu Melkamu 2 , Patrick Kilmartin 2 Jaya Koti 2 ) 1Lumigen Inc., Southfield, MI 48033, 2Beckman Coulter, Chaska, MN 55318 BACKGROUND Beckman Coulter is developing a new immunoassay system that will run current Access immunoassays as well as additional new menu. Goals for this new system include improved turnaround-times for all assays, thereby meeting STAT test requirements while improving overall platform throughput. A key component of the new system is a new chemiluminescent substrate employed to generate the light signal response. This new substrate is composed of a buffered surfactant enhancer system supporting an alkaline phosphatase-sensitive acridan. When the acridan is triggered in-situ, it forms a dioxetanone which immediately decomposes and emits light. Lumi-Phos 530 (also known as LP-530) has desirable sensitivity, background luminescence and open bottle stability, but needs 6.3 minutes for signal generation on automated immunoassay systems. The new substrate formulation was optimized for immunoassay specificity, compatibility, sensitivity and is suitable for use with all forms of ALP employed by Access assays with a much shorter time to signal generation. Comparison of the Lumi-Phos 530 substrate to the new chemiluminescent substrate LumiFAST was done on a immunoassay prototype analyzer to understand the performance characteristics. METHODS Luminometer read time is approximately 5 minutes shorter for the new substrate than for Lumi-Phos 530. Three- to six-fold increases in signal-to-noise performance were demonstrated across the Access immunoassays. Samples with known high endogenous ALP activity displayed greater than 50% reduction in spurious elevations (fliers) when using the new chemiluminescent substrate as compared to the values observed with the same samples using Lumi-Phos 530. 73% reduction in false reactives were seen with LumiFAST. The chemiluminescent substrate LumiFAST has been optimized to generate signal rapidly, improve signal-tonoise performance, and reduce non-specific background from endogenous alkaline phosphatase (ALP) in comparison to Lumi-Phos 530. This new substrate presents the opportunity to significantly shorten the time to first result while simultaneously improving assay sensitivity. Benefits: ▪ Shortened Time to first result by ~5 minutes ▪ Improved assay sensitivity by reducing signal to noise ▪ Improved specificity for assay ALP – Reduced magnitude of falsely elevated signals due to endogenous alkaline phosphatase ▪ Improved discrimination of non-reactive and reactive results © 2019 Beckman Coulter. All rights reserved. Beckman Coulter, the stylized logo, and the Beckman Coulter product and service marks mentioned herein are trademarks or registered trademarks of Beckman Coulter, Inc. in the United States and other countries. RESULTS CONCLUSION Lumi-Phos 530 on Access 2 LumiFAST on Immunoassay Prototype analyzer 6.3 Minutes signal generation 1 Minute signal generation Minimum 18 hour room temperature equilibration before use No room temperature equilibration before use “This product is in development and is not available for sale. Pending achievement of CE compliance; not yet available for in vitro diagnostic use. Pending clearance by the United States Food and Drug Administration; not yet available for in vitro diagnostic use in the US. For Investigational Use Only.” Lumi-Phos 530 LumiFAST Figure 1 illustrates the active component and mechanism for chemiluminescence of Lumi-Phos 530 and LumiFAST substrates Figure 2 illustrates the emission spectrum of both substrates with an emission maxima around 430 nm for LumiFAST(blue) and 530 nm for Lumiphos-530(red) Figure 3 illustrates the signal generation for bovine ALP with both substrates. Peak intensity was seen with LumiFAST within 60 seconds after injection. Results obtained on a BMG Plate Reader over 6 minutes Calibration Curve Signals Figure 4 and 5 illustrates the signal generated with hsTnI and TSH calibration curves for both LumiFAST (blue) and LumiPhos 530 (red) Figure 6 illustrates the signal-to-noise improvement across the current immunoassay menu. A 2.5 fold median increase in signal-to-noise was seen with LumiFAST compared to Lumi-Phos 530 Improved Time to first result with LumiFAST on immunoassay prototype analyzer Improved Sensitivity with LumiFAST on prototype immunoassay analyzer Figure 7 illustrates differences and distinction in RLU between low concentration TSH samples and zero calibrator with both substrates hsTnI Detection Capability (pg/ml) Figure 8A-D illustrates the Limit of Blank and Limit of Detection for hsTnI with both substrates on the immunoassay prototype analyzer. Better detection capability was seen with LumiFAST Enhanced Assay Specificity with LumiFAST on immunoassay prototype analyzer Disturbed Tube Model- HBsAg 78% Reduction in false reactives with LumiFAST compared to Lumi-Phos 530 Reactive rate of HBsAg with high endogenous ALP Levels Figure 9A and 9B illustrates differences in LoQ (20% CV) for hsTnI (pg/ml) on immunoassay prototype analyzer Better Discrimination of Non-Reactive Samples from Cut-off with LumiFAST on immunoassay prototype analyzer Figure 11A and 11B illustrates differences in signal to cutoff for HBsAg with LumiFAST and Lumi-Phos 530 for presumed normal samples on immunoassay prototype analyzer Figure 12A and 12B illustrates differences in signal to cutoff for HIV with LumiFAST and Lumi-Phos 530 for presumed normal samples on immunoassay prototype analyzer Figure 10A and 10B illustrates fewer reactive samples with LumiFAST Substrate compared to Lumi-Phos 530 TSH Detection Capability (mIU/L) Improvement in assay sensitivity (signal-to-noise) with LumiFAST compared to Lumi-Phos 530 An in-house model of incorrect primary tube handling, which leads to neutrophil contamination of plasma samples, is referred to here as the “disturbed tube model”. Neutrophil ALP generates non-specific signal in some immunoassays. False positive results due to this endogenous ALP was evaluated by testing samples subjected to the “disturbed tube model” using normal plasma. HBsAg reactivity (S/CO) with both LumiFAST and Lumi-Phos 530 is shown below Approximately 500 presumed non-reactive samples were tested using the HIV and HBsAg assays with both Lumi-Phos 530 and LumiFAST chemiluminescent substrates Assay Name Lumi-Phos 530 LumiFAST Intact PTH 14 8 Total βHCG 17 11 hsTnI 17 11 Time to first result in minutes Patient samples screened for high levels of endogenous ALP were used and were tested for HBsAg reactivity using both Lumi-Phos 530 and LumiFAST substrates LumiFAST improved signal-to-noise 3 ~Read Time for Lumi-Phos 530 ~Read Time for LumiFAST LumiFAST LoB LoD LoQ 10% CV LoQ 20% CV Mean 0.25 0.32 0.43 0.19 Std Dev 0.10 0.11 0.12 0.05 Lumi-Phos 530 LoB LoD LoQ 10% CV LoQ 20% CV Mean 0.50 0.51 1.91 0.78 Std Dev 0.31 0.23 0.44 0.16 Disturbed NonReactive Reactive NonReactive Reactive No 7 4 1 6 8 7 Yes 6 5 1 0 2 9 4 6 LumiFast Lumi-Phos 530 NonReactive Reactive Total LumiFAST 441 3 0 471 Lumi-Phos 530 364 111 475 LumiFast LoB LoD LoQ 10% CV LoQ 20% CV Mean 0.00035 0.00074 0.0034 0.00130 Std Dev 0.00008 0.00018 0.0009 0.00031 Lumi-Phos 530 LoB LoD LoQ 10% CV LoQ 20% CV Mean 0.00073 0.00157 0.0079 0.0028 Std Dev 0.00017 0.00038 0.0029 0.0008 LumiFAST formulation was optimized to work with Access immunoassays. Luminometer read time was assessed by determining the change in relative light unit (RLU) signal over 9 to 72 seconds using an ALPbased enzyme test method and several commercialized Access immunoassays. Improved signal-to-noise performance was demonstrated by comparing calibration curves from several immunoassays generated using Lumi-Phos 530 and the new chemiluminescent substrate LumiFAST. The impact of non-specific signal from endogenous ALP was determined by assessing a panel of patient samples previously identified to contain these interferents, using assays tested with both substrates. “Assay results shown were generated using immunoassay prototype systems and may not represent final product claims”
AN INDEPENDENT ANALYTICAL EVALUATION OF BECKMAN COULTER’S NEW HIGH THROUGHPUT IMMUNOASSAY ANALYSER Niamh O Mahony, Sarah Ni NiShuilleabhain, Ray Divilley - Mayo University Hospital (MUH), Ireland Precision Within run percent coefficient of variation (% CV) and within laboratory % CV met manufacturers published claims for all analytes. Within run % CV ranged from 1.1% to 5.1%. Within laboratory % CV ranged from 1.8% to 7.3%. 88% of within laboratory CVs were below 4% (Table 1). Precision specifications published by the European Federation of Laboratory Medicine were met. Detection Capabilities: LOB & LOD The manufacturers claims for LOB and LOD (Table 2) were met for all analytes. Detection Capabilities: LOQ The manufacturers claims for LOQ were met for all analytes. The %CV observed in samples with concentrations at the manufacturer’s quoted 20% LOQ ranged from 3.5% to 14.6% (Figure 1). RESULTS When evaluated in accordance with CLSI guidelines, the DxI 9000 Access Immunoassay Analyser achieved, and in some cases, surpassed, the manufacturer’s claims for all analytes, demonstrating excellent analytical performance. CONCLUSION METHODS Table 1 Precision Table 2 Detection Capability - IFU Claims Figure 1 Within lab precision at claimed LOQ (20% CV) Table 3 Regression analysis DxI 9000 v DxI 800 Background Beckman Coulter has recently developed the DxI 9000 Access Immunoassay Analyser, a high throughput system designed for busy laboratories. With a newly formulated chemiluminescent substrate, innovative engineering and novel features it promises to be precise, reliable and productive. As a pioneer in embracing new technology, Mayo University Hospital (MUH) installed the first DxI 9000 in Ireland, with the aim to verify the claims made by Beckman Coulter in an independent laboratory setting. 8 assays currently in use in the biochemistry laboratory of MUH were verified between August and December 2022. The manufacturers claims for precision, detection capabilities and linearity for Access Total βHCG (5 th IS), Access Free T4, Access Ferritin, Access Folate, Access Vitamin B12, Access PCT, Access hsTnI and Access TSH 3 rd IS were evaluated on the DxI 9000, in accordance with CLSI guidelines. Within run and within laboratory precision studies were performed for all tests in accordance with CLSI EP15 using 3 levels of pooled patient samples for PCT and 3 levels of Technopath Multichem IA Plus for other analytes. Claims for Limit of Blank (LOB), Limit of Detection (LOD) and Limit of Quantitation (LOQ) were assessed using pooled serum and diluent following CLSI EP17 and EP15. Linearity was evaluated as per CLSI EP06 using Technopath Immunoassay L3 QC material and fT4 was evaluated using Beckman Coulter Access fT4 calibrator set. Patient and EQA results generated by DxI 9000 were compared to those produced by DxI 800 analysers for four analytes, using Passing-Bablok regression analysis and in accordance with EP09c. Carryover studies were also performed on β-HCG and hs-Troponin I using an internal laboratory protocol involving running three replicates of a high concentration sample, followed by three replicates of a very low concentration sample. Three levels of Technopath Multichem QC was run each day and a maintenance schedule was followed for the duration of the study. Linearity The linearity claims passed for all assays. Comparison v DxI 800 Results obtained on the DxI 9000 compared well with those generated on the DxI 800. Slopes ranged from 0.93 to 1.08 (Table 3). Mean % CV Within Run %CV Within Lab Folate 3.63 ng/ml 1.7 2.4 5.82 ng/ml 1.4 2.2 12.85 ng/ml 1.1 1.8 hCG 4.59 IU/l 2.0 2.4 25.05 IU/l 2.5 2.6 503.5 IU/l 1.8 2.6 PCT 0.418 ng/ml 3.9 5.4 1.855 ng/ml 2.8 3.3 15.96 ng/ml 2.5 3.0 hsTnI 15.54 ng/ml 1.5 2.1 148.48 ng/ml 2.1 2.4 1063.44 ng/ml 2.0 2.3 TSH 0.067 mIU/l 2.8 3.5 3.557 mIU/l 5.1 5.6 19.961 mIU/l 3.2 3.5 FT4 8.13 pmol/l 2.4 3.8 21.73 pmol/l 2.1 3.2 42.61 pmol/l 1.7 2.8 B12 218.11 pg/ml 2.4 3.2 534.62 pg/ml 2.9 3.8 1130.65 pg/ml 3.0 7.3 Ferritin 14.56 µg/l 2.5 2.5 157.86 µg/l 2.5 3.0 293.75 µg/l 3.2 3.7 Assay IFU LOB claim IFU LOD claim IFU LOQ (20%CV) claim Ferritin (ng/ml) ≤0.2 ≤0.4 ≤0.6 Folate (ng/ml) <0.8 <1.0 <2.0 hCG (IU/L) ≤ 0.5 ≤ 0.5 0.6 PCT (ng/ml) ≤ 0.005 ≤ 0.01 ≤ 0.02 hsTnI (ng/l) 0.5 0.9 (ser) 1.0 (ser) TSH (mIU/l) ≤ 0.005 ≤ 0.005 ≤ 0.01 B12 (pg/ml) ≤ 50 <68 <68 Carryover No clinically significant carryover was detected. 0.0% 2.0% 4.0% 6.0% 8.0% 10.0% 12.0% 14.0% 16.0% 18.0% 20.0% Within Lab Imprecision (%CV) Sample MUH Within Lab Imprecision (%CV) on 3 samples with concentrations at quoted LOQ (20%CV) Access Assay N Concentration Range (DxI800) Slope [95% CI] Intercept [95% CI] Correlation Coefficient (R) FT4 106 8.21 - 21.25 pmol/l 0.93 [0.83 - 1.03] 0.16 [-0.97 - 1.24] 0.91 hsTnI 103 2.3 – 37625 ng/l 0.94 [0.86 - 1.0] -0.94 [-1.38 - -0.34] 1.00 TSH 3 rd IS 108 0.026 - 13.995 mIU/l 1.01 [0.98 - 1.04] 0.033 [-0.005 - 0.068] 1.00 B12 89 58.4 - 182.9 pg/ml 1.082 [0.98-1.19] 14.01 [0.73 - 25.63] 0.93 System Maintenance No daily maintenance is required. Average system time required for weekly maintenance procedures was under 12 minutes. Average monthly maintenance procedures was under 15 minutes. WORLDLAB. EUROMEDLAB. ROMA 2023 2023-12402
BACKGROUND The recently launched DxI 9000 Access Immunoassay Analyzer is the latest Beckman Coulter offering for high and ultra high throughput labs. The DxI 9000 Access Immunoassay Analyzer addresses the demands from today’s laboratories for speed, reliability, reproducibility, quality and menu expansion. The novel Lumi-Phos pro substrate has shown the capability for increased sensitivity, while ZeroDaily Maintenance will save the laboratory time and PrecisionVision Technology will safeguard against flawed data reports. At CMC Vellore, India, we evaluated the analytical characteristics (Limit of Blank and precision) of the DxI 9000 Access Immunoassay Analyzer for 15 assays, which were then compared against IFU claims and biological variation obtained from the European Federation of Laboratory Medicine (EFLM) database 1 . Method comparison for these 15 assays on the DxI 9000 was also performed with four other commercial immunoassay platforms analyzers. DxI 9000 was assessed using main recommendations from CLSI, and showed excellent performance, met manufacturer claims, and specifications from EFLM. There was overall good correlation between DxI 9000 and the 4 commercial immunoassay platforms used in this study when investigating the respective tests. CONCLUSION THE ASSESSMENT OF ANALYTICAL CHARACTERISTICS OF NEW HIGH-THROUGHPUT IMMUNOCHEMISTRY ANALYZER DXI 9000 (BECKMAN COULTER INC., USA) Authors: Pamela Christudoss 1 , G.Jayakumar Amirtharaj 1 , Murali Kodali 2 , Anna Ruzhanskaya 3 Limit of blank (LoB) was evaluated for twelve analytes using CLSI EP17-A2 guideline 2 . Precision was evaluated for twelve analytes using samples with three levels of BioRad Immunoassay Plus quality control (QC); five measurements per each QC sample were done on each of the four pipettors in one day. CV% obtained in the current study were compared to desirable and minimal CVi% (1/2 and 3/4 of CVi% published by the EFLM, respectively)1,3,4 DxI 9000 results for fifteen analytes were compared to those results were obtained on Atellica and Immulite XPi (Siemens Healthcare GmbH), Cobas 8000 (Hoffmann-La Roche Ltd), and BRAHMS Kryptor (Thermo Fisher Scientific Inc.) analyzers, using Passing-Bablok regression analysis in accordance with CLSI EP 09 guideline 5 All laboratory measurements were done according to the laboratory's Quality Manual, standard operating procedures (SOPs) and manufacturer’ instructions for use (IFU). QC was performed through daily measurement of 3 levels of QC specimens. For statistical calculation EP Evaluator and Analyze-It software were used. METHODS RESULTS Figure 1. Precision: comparison with desirable CV% 2023- Table 1. LoB comparison with IFU’ claims Table 2. Regression analysis: DxI 9000 vs 4 analyzers LoB for twelve analytes fully met manufacturer’s claims are provided in the respective IFUs (Table 1). Precision (CV%) for twelve analytes from the current study were compared to desirable and minimal CVi% (1/2 and 3/4 of CVi%) published by the EFLM1,3 (Figure 1). CV% ranged from 1.5 to 6.4%%. All the analytes met EFLM specifications for desirable CV, except two levels of Access AFP, and one level of Access Folate, Access Free T4, and Access Vitamin B12, which, however, did fully meet the minimum standard relative to biological variation (3/4 CVi) 1,3: 2.9 vs 3.45, 6.4 vs. 8.85, 3.1 vs 3.7, and 4.1 vs 5.4 %%, respectively. All the analytes correlated well, with ranging of coefficient of regression (r) and slope from 0.95 to 0.998, and from 0.85 to 1.28, respectively. Analyte Units LoB IFU LoB AFP ng/ml 0.024 0.5 AMH ng/ml 0.000 0.02 Cortisol μg/dL 0.017 0.4 Folate ng/ml 0.000 0.8 Free T4 ng/dL 0.018 0.22 TbHCG mIU/mL 0.036 0.2 hFSH mIU/mL 0.005 0.2 hLH mIU/mL 0.019 0.040 Prolactin ng/ml 0.047 0.25 Estradiol pg/ml 0.000 15 TSH mIU/mL 0.0000 0.005 Vitamin B12 pg/ml 34.2 50 Literature: 1. EFLM database; https://biologicalvariation.eu 2. CLSI EP17-A2 Verification of detection capability for clinical laboratory measurement procedures; 2nd edition 3. CLSI C24-ED4:2016 Statistical Quality Control for Quantitative Measurement Procedures: Principles and Definitions, 4th edition 4. www. Westgard. com 5. CLSI EP09C-ED3:2018 Measurement Procedure Comparison and Bias Estimation Using Patient Samples, 3 rd edition Analyte Units N Concentration range (DxI 9000) Slope (95% CI) Intercept (95% CI) Correlation coefficient (r) TSH 3rd Gen μIU/mL 112 0.002 - 45.227 1.01 (0.99 - 1.02) 0.02 (-0.00 - 0.06) 0.998 FT4 ng/dL 105 0.35 - 7.70 1.022 (0.96 - 1.1) -0.23 (-0.31- -0.16) 0.97 Testosterone ng/dL 103 25.80 - 834.00 1.02 (0.96 - 1.1) 23.51 (13.42 - 37.24) 0.97 Vit D ng/ml 100 4.17 - 75.2 0.98 (0.93 - 1.04) 2.3 (1.16 - 3.6) 0.97 Cortisol μg/dL 110 0.70 - 67.90 0.85 (0.81 - 0.88) 0.248 (-0.09 - 0.54) 0.99 AFP ng/ml 108 0.00 - 461.00 1.19 (1.13 - 1.24) 0.00 (-0.16 - 0.2) 0.99 AMH ng/ml 100 0.048 - 12.400 1.2 (1.16 - 1.27) 0.02 (-0.04 - 0.1) 0.98 Folate ng/ml 103 1.60 - 19.60 0.94 (0.9 - 1.0) 0.76 (0.33 - 1.05) 0.96 TbHCG mIU/mL 80 0.150 - 990.600 1.28 (1.25 - 1.30) 0.96 (0.19 - 1.55) 0.99 Vitamin B12 pg/ml 118 100 - 1748 0.76 (0.74 - 0.78) -22.0 (-29.5- -14.6) 0.99 Vitamin D ng/ml 100 3.10 - 80.10 0.98 (0.93 - 1.04) 2.35 (1.1 - 3.6) 0.97 hFSH mIU/mL 122 0.59 - 161.00 1.07 (0.99 - 1.12) 0.4 (0.1 - 0.78) 0.98 hLH mIU/mL 105 0.12 - 78.60 1.12 (1.08 - 1.19) -0.08 (-0.23 - 0.0) 0.98 Prolactin ng/ml 93 0.95 - 101.80 1.070 (1.00 - 1.14) 0.03 (-0.52 - 0.52) 0.95 PCT ng/ml 114 0.030 - 64.400 1.018 (0.99 -1.06) -0.05 (-0.06- -0.04) 0.997 DxI 9000 vs. Atellica (Siemens Healthcare GmbH) DxI 9000 vs. Cobas 8000 (Hoffmann-La Roche Ltd) DxI 9000 vs. Immuite 2000 Xpi (Siemens Healthcare GmbH) DxI 9000 vs. Brahms Kryptor (Thermo Fisher Scientific Inc.) 1Department of Clinical Biochemistry, Christian Medical College, Tamil Nadu, India; 2Beckman Coulter Pvt Ltd, Mumbai, India; 3Beckman Coulter LLC, Moscow, Russia © 2023 Beckman Coulter. All rights reserved. Beckman Coulter, the stylized logo, and the Beckman Coulter product and service marks mentioned herein are trademarks or registered trademarks of Beckman Coulter, Inc. in the United States and other countries. All other trademarks are the property of their respective owners. 2023-12212