Leading Edge An Alpha Laboratories Ltd. Publication 2025 - Issue 1 More articles inside... Calprotectin Workflow Efficiencies with fCAL® turbo and CALEX® to Patients - Page 4 Improved workflow at Addenbrooke’s - Page 7 Innovating Allergy Testing with BÜHLMANN Flow CAST® - Page 12 Liquid-Stable Quality Controls - Page 16 Pancreatic Exocrine Insufficiency in Diabetes Mellitus - Page 6 Alpha Solutions Helps Improve Logistics for Marsden360 Page 10 The Evolution of Urinalysis: From Dipsticks to Digital Solutions - Page 14 Addressing the Challenges in the Diagnosis of Invasive Aspergillosis - Page 18 Featured article: Calprotectin, from the very beginning... With Dr Arne Roseth - Page 2 See more details on page 9
Calprotectin, from the very beginning… Amanda Appleton, Senior Product Manager, Alpha Laboratories Ltd., caught up with Dr Arne Roseth, a pioneer in the adoption of calprotectin testing for diagnosing and monitoring inflammatory bowel diseases. Dr Arne Roseth, a Norwegian gastroenterologist who is now semi-retired, has more than 25 years’ experience in calprotectin testing and its applications. He was himself diagnosed with Crohn’s disease in 1973, which is why he has always had more than a keen interest in gastroenterology. “Back in May 1973 I was hospitalised for 77 days to drain an abscess, but this led to the diagnosis of Crohn’s disease in my small bowel – I was 18 years old. Following the diagnosis I had an 8 hour surgery, in November 1973, to deal with the abscess and the fistulas. I was then advised it had all been removed and there was an 80% chance of never having a relapse. However, when I started to study medicine, I discovered I had an 80% chance of relapse within two years. I began my career at the University Hospital in Oslo, where I learned all about inflammatory bowel disease (IBD) and the diagnostics available at the time. My Professor (Prof. Henning Schjønsby) taught that patients are measured against clinical indices: it is active disease if they have abdominal pain and diarrhoea and don’t feel well, and it is in-active disease if they feel OK. At first, I was very impressed with this, but then I started questioning how could he know how accurate this was? He did get a little bit annoyed at being challenged! A few weeks later he asked me to prepare a talk on IBD and the disease activity. Back then there was no internet for research, it was manual which was cumbersome, but I did it and I presented the data at our internal weekly meeting. The bottom line was the indices were not validated with endoscopy. During my research I found a group of paediatricians had measured Alpha11 antitrypsin in stools and found a very good correlation with endoscopy. This is useful because paediatricians really don’t like to scope the children, so a noninvasive test is much better. Professor Schjønsby thought this was interesting, so I offered to set up a method to run the assay in stools in our laboratory. Fortunately, I knew the Norwegian champion in Alpha-1 antitrypsin (Prof Magne Fagerhol) because he sailed the same boats as my dad, so we used to compete together (and he beat us!), so I approached him and asked if he would help. I collected some stool samples and we made gels for immunodiffusion. Prof Fagerhol said, “if it is the neutrophils you are really looking for, I have isolated a protein from them, maybe we should look to see if there is any L1 protein present (this is now known as calprotectin). ” We loaded up the first ELISA plate and it became as yellow as a lemon, so we diluted the samples and ran them again – yellow. Diluted and ran again – yellow, and again and again. Late in the evening we had a plate with some clear wells and some yellowwells. I looked at my records and the yellowwells corresponded to the 8 IBD patients I had samples for. So that first day (it was March 1987) we found that yes, we can measure calprotectin in stool extracts and we could differentiate between IBD and non-IBD. So it was a pretty good days work! Following this breakthrough, I was given a research position for 5 years. This was spent improving the method, including the extraction buffer and the sensitivity. Then, by accident, we discovered that calprotectin is also raised in colorectal cancer. So I spent a few years doing clinical research in a rat model. We could predict when the rat would get the cancer before they got sick, which was pretty amazing. However, I preferred to work with humans rather than with rats. At this time some publications started to appear around using calprotectin as a diagnostic tool for IBD. Prof Ingvar Bjarnesson at Kings in London was the first to look at disease activity. They had a large group of patients and were able to predict that if calprotectin was below 250µg/g then only 10% would relapse within a year. If it was >250µg/g then ~80% would relapse within a year. So, I started to use this to monitor my patients and then increase or decrease the treatment according to the calprotectin levels. Furthermore, I began to look at patients who had mucosal healing when they were scoped. I asked them to send a stool sample (after waiting 3 days) which we tested for calprotectin. We could see that the concentration was below 200µg/g for these patients, so endoscopic healing, and when it was 2 Leading Edge
below 100µg/g it was histologic healing. We published this data in 2003. As calprotectin testing usage increased there were complaints because there was some variability batch to batch between the kits used then. I approached BÜHLMANN around 2006 and they had developed their own kit. The quality and the controls were so much better. These were the kits that were then used in many of the early studies so there is a lot of validation for the quality and standardisation of the BÜHLMANN assays. For more information please visit: www.calprotectin.co.uk After the ELISA assay, the QuantumBlue® rapid lateral flow test was developed and then the patient self-test (IBDoc). This came in useful for one of my Crohn’s patients who was planning to sail around the world. First, I had to get her stable with the drugs and then I taught her how to use the IBDoc®. She sailed around the world with her husband and 3 children and every time they were ashore she would run a calprotectin test. She did have a relapse in the Azores, but we doubled the dose of Humira and she’s been fine ever since. Actually, I have two patients who have sailed around the world with the aid of the IBDoc, so that is kind of cool. Since the initial ELISA assay was launched in 2007, BÜHLMANN has continued to provide quality and novel assays to support calprotectin testing across the healthcare network. Arne has switched his focus from IBD in the last 7-8 years so has been looking at coeliac disease, investigating different ways of diagnosis, and with food allergies. 2007 The first BÜHLMANN assay, fCAL® ELISA, is launched in the UK to enable calprotectin testing is with assay protocol 10-600 μg/g 2009 Quantum Blue fCAL® range was first introduced for laboratories with low sample throughput or for use in point-of-care setting, e.g. IBD clinics, or on wards 2010 High range assay protocol is released for fCAL® ELISA giving results up to 1800 μg/g, enabling monitoring of IBD patients 2011 Quantum Blue fCAL® high range (100-1800 μg/g) became available, ideal for monitoring positive IBD patients 2012 Double plate fCAL® ELISA format for higher throughput lab testing made available 2013 Quantum Blue fCAL® extended range (30-1000µg/g) was introduced, with results used to aid the diagnosis and monitoring of IBD patients with a single kit format 2014 fCAL® ELISA WEX format and CALEX extraction device were launched. Designed for compatibility with the BÜHLMANN assay and offering a significantly improved workflow unlike the more traditional extraction method 2015 IBDoc® Calprotectin home test, the first CE marked home test for patients with IBD, became available. The extended range cassette (30-1000µg/g) is used in the IBDoc 2016 BÜHLMANN fCAL® turbo is launched in the UK for high throughput calprotectin testing on mainstream analysers. This is the fastest calprotectin assay on the market giving results in just 10 minutes 2017 CALEX® Cap is improved in precision and now even closer to the gold-standard weighing method 2020 Launch of the 3rd generation Quantum Blue Reader. This reader is more POC friendly with touch screen, barcode reader or LIMS connection for data entry 2024 The newest addition, UKCA marked CALEX® faecal calprotectin collection kits, streamline the sample collection and testing process and maximise valuable resources in the laboratory, reshaping calprotectin testing workflows Calprotectin Testing - Timeline www.alphalabs.co.uk © 2025 Copyright Alpha Laboratories Ltd. 3
Calprotectin Workflow Efficiencies with fCAL® turbo and CALEX® to Patients Amanda Appleton, Senior Product Manager, Alpha Laboratories Ltd. Claire Paterson is Chief Biomedical Scientist at Aberdeen Royal Infirmary, where she leads the Routine Automation Team in the Clinical Biochemistry Laboratory. Within the last year, the team there has implemented a number of changes to improve their calprotectin testing service. Claire talks to Amanda Appleton, Senior Product Manager, about how things have moved on. The Background “Aberdeen Royal Infirmary is the largest hospital in NHS Grampian covering a huge geographical area, and calprotectin testing for the whole region is performed here. The area extends up as far as Forres and down past Stonehaven, which includes over 90 GP practices. We are currently running around 200 – 250 calprotectin tests per week and until the start of 2024 we were using the Alegria® ELISA based method (Orgentec). We have used this since the assay was first introduced, around ten years ago. However, we have had a significant increase in the volume of calprotectin requests and since the contract was coming to an end, we wanted to look at something that would improve efficiency. The Alegria is limited to 30 samples per run, so we were running it three times a week. However, we would rarely keep on top of demands. The extraction process was extremely time consuming. Faecal samples were supplied to us in pots which we had to pick, we were manually pipetting the buffer into the tubes, then they would go onto a roller/mixer for 30 minutes. After this we had to vortex, centrifuge and manually pipette from the tubes onto the ELISA plates. This occupied a BMS (Band 5 or 6) all afternoon, plus the assay also took quite a long time to run. The Alegria wasn’t interfaced, so once generated, the results would need to be manually transcribed, then transferred into APEX (middleware system) and verified by another member of staff, before they could 4 Leading Edge
If you would like more information on the BÜHLMANN fCAL® turbo assay, then please visit: calprotectin.co.uk/fcal-turbo For more information about CALEX patient packs please visit: calprotectin.co.uk/calex-pack be reported. There was also only one other user on the EQA and the results between us didn’t always correlate, but with only two users it is difficult to understand the cause. The switch The reason we changed our calprotectin method to the BÜHLMANN fCAL® turbo on the Alinity (Abbott), was because this is already embedded in our automation. It consolidates the testing onto an existing platform that everyone within the department is already trained on and familiar with. It also now gives us a backup of instruments. We run twice a week testing around 100 samples at a time and the results are available really quickly. This is so much more efficient and there is no carryover into the following week. We currently still perform some of the extractions in the lab with the CALEX devices, but even this is so much faster than the Alegria extraction process – we pick, we vortex, we centrifuge, and samples are ready to be analysed. The CALEX samples that are coming directly from the patients just need centrifuging, and they are ready to go. Our turnaround times have almost halved and this is due to a combination of the uptime on the analysers, the direct reporting from the Alinity into APEX, unlimited number of sample per run, much quicker processing of samples and the assay time. It is a complete workflow change - it really is very easy to use. We are still batching the tests for analysis, although once we have fully implemented the CALEX tubes to all patients we will likely run every day, in small batches in a random-access mode, as there is the possibility to put the tubes onto the GLP track. The CALEX can be easily uploaded into the GLP tube database, they will be loaded onto the track alongside serum and urine tubes as and when they arrive in the department, pass through the pre-analytics and then to the analyser – I am really hoping to be able to do this in 2025. The assay is so stable that we will just run the QC once in the morning and again in the afternoon as part of our current IQC schedule. The large BÜHLMANN group on the EQA gave us much more confidence in benchmarking ourselves against other labs, but to be honest one of the biggest selling points for us is that the CALEX can be given straight to the patients. We are used to the QFIT devices, and they work well with the patients, so that side makes sense because nobody wants to be picking poo! It saves a member of staff who can do other things and the CALEX are just so easy to pop on the machine. CALEX Patient Packs Within NHS Grampian, calprotectin testing is a secondary care test requested by Gastroenterology. However, it is often implemented through primary care so the patient can collect and return the CALEX via their GP surgery. In the beginning we initiated the patient use of the CALEX with those that were coming into the clinic. They would collect the tube and the instructions, but return the completed tube to their GP surgery, where it would be delivered back to us via the current sample transport methods. Our compliance is good, but we have noticed that our non-compliance rates have reduced by more than half using the CALEX, compared to when patients were asked to do the stool pot and return it to the labs. When we do have non-compliance it is because the sample either isn’t labelled properly or it is contaminated/leaking, but the level of issue we have with the CALEX is minimal compared to similar tests. Currently the instructions for use are coming from Gastro, the (labelled) CALEX and return bag is being collected from the GP by the patient. Eventually we will have the system implemented through our GP ordering system who will put a kit together containing the CALEX, instructions and a return bag for the GP to order it complete from them. We are delayed in this because there have been some new secondary care hubs set up, but we are just working through the (hopefully last) logistics of getting these supplied. It really has been a very easy switch over of the assay – it has been a no brainer to move to the BÜHLMANN fCAL turbo on the Alinity.” Read the Poster that Claire Paterson and her team presented at LabMedUK24 The CALEX® direct to patient pack www.alphalabs.co.uk © 2025 Copyright Alpha Laboratories Ltd. 5
Pancreatic insufficiency is the reduction of production or transportation of the digestive enzymes, which results in the inability to properly digest a meal (fats, proteins and carbohydrates). The insufficiency is not absolute, it is variable, which then has a graded impact on digestion and hence symptoms. Patients can suffer from a variety of gastric issues, ranging in severity, but including abdominal pain, weight loss, diarrhoea, pungent loose stools, flatulence, loss of appetite and fatigue. Pancreatic Exocrine Insufficiency (PEI) is often associated with other pathologies and high amongst these, not surprisingly is Diabetes. PEI is associated with reduced glycaemic control in diabetes, and going undiagnosed may also add to the burden of ill health experienced by these patients due to vitamin and micronutrient deficiencies. A recent publication by Dr V Parihar et al. from Tallaght University Hospital in Dublin (Acta Diabetologica 2024 61:1301-1307) concluded that routine screening for PEI using faecal elastase 1 testing should be considered for all diabetic patients so they can be diagnosed and managed appropriately. In a publication in the BMJ in 2021 Dr Mary Phillips headed a Multidisciplinary panel of experts review of literature for the management of PEI in the UK and found the incidence of PEI in T1 diabetes to be between 26-57% and between 1236% in T2 diabetes. Pancreatic Exocrine Insufficiency in Diabetes Mellitus Amanda Appleton, Senior Product Manager, Alpha Laboratories Ltd. For more information please visit: www.calprotectin.co.uk/fpela 6 Leading Edge
Improved workflow at Addenbrooke’s Georgette Glover, Senior Biomedical Scientist, Biochemistry department at Addenbrooke’s Addenbrooke’s Hospital at Cambridge University Hospitals NHS Trust (CUH) have been using the BÜHLMANN calprotectin assays for a number of years. They initially used the fCAL® ELISA and the CALEX on a DS2 analyser, but switched technology in December 2018 to the BÜHLMANN fCAL turbo on their Siemens Advia 2400. More recently (2022) the assay was moved onto the Siemens Atellica systems. The lab currently tests around 30,000 calprotectin tests per annum and have now also switched to using the BÜHLMANN fPELA assay for elastase analysis too. Georgette Glover, a Senior Biomedical Scientist in the Biochemistry department at Addenbrooke’s talks about the change. We currently test around 4000 elastase samples a year, almost a 1000 more than we were doing in 2023 before we switched from themanual ELISAmethod. We were very pleased to have switched to a more automated method before the increase. We provide the testing for Cambridge University Hospitals NHS Trust and surrounding primary care, but we also test for surrounding NHS Trusts too, so we cover quite a large area. The majority of the requests (~80%) come from secondary care. Previously, with the ELISA method we would run in batches. These were fairly frequent due to the volume of requests we receive, and we couldn’t afford to get behind when each batch is half a day’s work for a member of staff. The ELISA method did require analysis of some samples to be repeated due to a combination of the manual nature of the method, sample consistency and high CV’s. This could cause a delay to reporting the result. Results were also manually transcribed into the laboratory information system (LIMS) which generated an additional risk of transcription errors. Primarily, we wanted to change from the manual ELISA due to the workflow improvements offered by the automated chemistry analysers, we were also mindful of the risk to our current service due to the use of an ageing plate reader. Given that we were already running the BÜHLMANN calprotectin method with the CALEX extraction the BÜHLMANN fPELA method was the obvious choice to evaluate. Introducing the BÜHLMANN fPELA meant that we were able to improve our workflow as we had done with the calprotectin assay, resulting in time for staff to complete other essential duties. We also found that 30% (approximately 1200) of our elastase requests shared a calprotectin request too, so we can extract into a single CALEX and analyse for both. This helped reduce our costs which was a bonus. From an ordering point-of-view it is also more streamlined as we have a single point of contact for ordering all BÜHLMANN reagents. We are also providing a more resilient service with no single point of failure as we are running on automated systems with multiple chemistry analysers available as back up, if required. Using the automated chemistry system means that the results are also automatically transferred into the LIMS , this has benefits in terms of speed of reporting and eliminates the risk of transcription errors. Setting up the fPELA on the Atellica and validating the assay was really easy because we had already been through the process when we switched from the Advia 2400 to the Atellica for the calprotectin assay. The protocol was easy to set-up, the assay calibration and controls were within the defined limits, so we were able to go ahead with the method verification work. We went live with the assay in September 2023 and since then our EQA performance has been very good. Article continues next page www.alphalabs.co.uk © 2025 Copyright Alpha Laboratories Ltd. 7
The improved stability of the CALEX sticks over the extraction device for the ELISA method was also beneficial in terms of allowing changes to our preparation patterns. We still only analyse samples twice a week, but we extract the samples daily and store the CALEX in the fridge until we are ready to run them on the designated day. We load the CALEX onto the Atellica sample input module and can analyse both calprotectin and elastase simultaneously once QC have been performed – it runs very smoothly. We do test mucoid and liquid samples for elastase and add comments as appropriate. If they are particularly liquid then we will use a pipette to measure the volume for extraction. If the result is: <200ug/g we won’t report and state it is too liquid >200ug/g we report but advise interpret with caution >500ug/g then we just report and not comment on the sample consistency Using the automated method has dramatically streamlined our service, both in terms of extraction and analysis. The elastase samples canbe incorporated into the calprotectin workflowwhich has really has saved us time and improved the service offered to our customers. If your workload is increasing, then consider the fPELA method as an option before numbers becomes unmanageable. Implementing the fPELA is really straight forward, especially if you have prior experience with the fCAL turbo method - just follow the protocol. For us this decision was hugely beneficial to the department and our patients. It has freed up staff time to do other duties or focus on laboratory development and improvement projects. Visit: calprotectin.co.uk/fpela today and get started on your lab’s journey to a more efficient, reliable, and scalable testing solution. When investigating patients with abdominal symptoms outside the scope of the suspected cancer guidelines, the quantitative faecal immunochemical test (FIT) is an established diagnostic tool. Should you need to test in an acute setting or require a fast turnaround quantitative FIT service, a qualitative FIT test such as the DIAQUICK FOB cassette can take the place of the guaiac-based cards that may have been used in the past. The DIAQUICK FOB cassette offers the specificity of a FIT in a simple yes/no manual test format. Unlike older guaiac-based methods, which recommended adherence to a special diet prior to testing to avoid interference from peroxidases or animal derived haem proteins, there are no dietary restrictions when using these lateral flow assays. The DIAQUICK FOB test uses antibodies that specifically bind human haemoglobin (Hb), with a sensitivity of 6μg Hb/g faeces. For more information, please visit: alphalabs.co.uk/Z01101CE Specific, Sensitive, Simple. 8 Leading Edge
9Functional assay for complement activity 9Screen for primary immunodeficiency 9Monitor anti-complement therapy 9Measuring range 10–60 U/mL 9Open vial stability 40 days at 2-10C For more information, please visit: alphalabs.co.uk/ch50 A BIG THANK YOU for joining us on our journey! We look forward to serving the scientific and healthcare community for years to come. Please visit alphalabs.co.uk/50th for more details. Alpha Laboratories is celebrating its 50th anniversary this year, marking half a century of commitment to supporting clinicians, scientists, and patients worldwide. Since our founding in 1975, we have grown into a trusted supplier of laboratory consumables, liquid handling solutions, diagnostic products, and lab equipment. A Year of Celebration A functional assay which measures the activity of the whole complement system can be an important screening tool to aid the diagnosis of primary immunodeficiencies as well as monitoring autoimmune disease activity or even response to anti-complement therapies. Classical pathway activity in serum is traditionally assessed by measuring the of lysis of antibody-sensitised sheep erythrocytes. The amount of test serum required to cause 50% haemolysis of the erythrocytes is defined as the relative activity (CH50). The FUJIFILMWako CH50 liposome immunoassay (LIA) removes the requirement for animal erythrocytes, which can vary greatly from batch to batch and result in very limited reagent stability, utilising instead antigen coated liposomes containing glucose-6-phosphate dehydrogenase (G6PDH). Antibodies in the assay reagent combine with the liposomes to create an antigen-antibody complex, triggering complement activation within the sample. The complement cascade results in the formation of the membrane attack complex (MAC) which lyses the liposomes, releasing enzyme which reacts with NAD and G6P in the reagent enabling photometric measurement proportional to activity. A Sensitive and Stable Solution for Functional Complement Activity Assessment www.alphalabs.co.uk © 2025 Copyright Alpha Laboratories Ltd. 9
Alpha Solutions™ Helps Improve Logistics for Marsden360 Lisa Thompson, Head of Commercial Development - Clinical Genomics, at The Royal Marsden NHSFT A new ‘liquid biopsy test’ called the Marsden360, which has been developed by The Royal Marsden and Guardant Health has already enabled over 2000 patients with suspected advanced lung cancer to have a ctDNA blood test before or at the same time that diagnostic biopsies are taken. NHS England have since rolled out the test to an additional 10,000 patients, in a bid to speed up treatment decisions. The Marsden360 liquid biopsy service is also currently available for private and clinical trial patients treated at The Royal Marsden, as well as providing a commissioned NHS ctDNA service to guide treatment decisions for eligible patients with suspected latestage breast cancer. Faster Detection, Analysis and Diagnosis From a simple blood sample, circulating tumour DNA (ctDNA) tests, also known as liquid biopsies, can detect tiny amounts of ctDNA shed by the cancer into the blood. Identification of key genetic mutations in a patient’s cancer can enable them to receive targeted treatments rather than standard chemotherapy. Matching patients to more targeted treatments based on their genomic profile can significantly improve their quality of life, increase survival rates and reduce side effects. The Marsden360 is performed for stage 3 and 4 solid tumours and provides an alternative to tissue sampling or can be completed in parallel to tissue sampling. Analysis of data from Guardant Health’s liquid biopsy testing also shows that time to diagnosis for patients with advanced lung cancer in the UK can be dramatically reduced by three weeks, improving the patient care pathway. Specialist Blood Collection Tubes It is essential to obtain a high-quality blood sample for liquid biopsies. Specialist blood tubes are required to ensure the preservation and integrity of the ctDNA which are often present in low concentrations and can degrade or be contaminated if not properly handled. Specialist tubes containing preservatives, such as Streck CellFree DNA BCT (blood collection tube), stabilise the nucleic acids and prevent cell lysis during transport and storage. This is a vast improvement on standard blood tubes that allow white blood cells and other components to break down, releasing DNA and RNA into the plasma. This can increase background “noise,” making it harder to isolate tumour-specific biomarkers. The preservative also prevents haemolysis during sample collection and handling which can interfere with downstream assays and affect results. In addition, Streck cfDNA BCT helps with logistics efficiencies by enabling extended storage and transport, without refrigeration. Standard tubes often require immediate processing to separate plasma from blood cells, usually within a few hours. Streck tubes stabilise cfDNA for up to 14 days at room temperature without compromising sample quality. Marsden360 is used for tumour mutation profiling through analysis of circulating cell free tumour DNA in patients with solid-tumour malignancies to identify patients who may benefit from treatment with approved targeted therapies. 10 Leading Edge
Logistics for Marsden360 Since it is a new national service, commissioned by NHS England for late-stage breast cancer and a pilot for a NonSmall Cell Lung Cancer ctDNA service, the tubes are not currently readily available in hospital clinics. They must be supplied specifically to sites conducting the testing. In addition, as the tubes are glass, it is essential that the correct transport packaging, compliant with UN3373 guidelines, is used for collection and return of the samples to the laboratory. Lisa Thompson, Head of Commercial Development - Clinical Genomics, at The Royal Marsden NHSFT, describes making the Marsden360 sample transport process efficient: “Previously we were purchasing the Streck tubes, absorbent pads and Royal Mail Safeboxes and distributing these to hospital sites. Micro-managing the logistics was very time consuming and not the best use of resources, especially in a busy Clinical Genomics Laboratory. Alpha Laboratories supplies consumables to our Clinical Genomics Laboratory and on speaking to our Key Account Manager, it became apparent that the company offers a logistics solution for kit assembly and fulfilment. This service proposition was an ideal fit for our requirements. We worked closely with the Alpha Solutions’ team so that they could develop a kit that is bespoke to our requirements. It contains two Streck cfDNA tubes with all the necessary compliant UN3373 transport packaging, for return back to the laboratory. Alpha Solutions also set our kit up on The Alpha Portal (TAP), their online ordering system. This enables us to log in and order patient kits for direct delivery to clinics, providing traceability and reducing the administrative burden. We had training on the portal, which was quick and straightforward. Alpha Labs worked rapidly to get us up and running within a couple of weeks. Clinical units order the Marsden360 blood collection kit (BCK) with our dedicated Royal Marsden team and the information is Find out more about bespoke kit development with Alpha Solutions www.alphalabs.co.uk/kits transferred to TAP. BCK kits are distributed within 24 hours of the order being placed, Monday to Friday. Orders are made in packs of 10 kits and the distribution to the hospital sites is either by Royal Mail or DPD, depending on the number of kits being distributed. This is to ensure the transport costs are kept to a minimum. We chose the kit solution from Alpha Solutions as it is competitively priced, but also having the Alpha Portal to address the logistical challenge of kit distribution. There are multiple benefits, it saves time, we can track the orders, and it saves space not having to stock the BCKs on site. The team has been very accommodating with our needs and extremely flexible in setting up the BCK service. They are always responsive, resolving any issues quickly (there haven’t been many) and keeping us up to date on a regular basis. Currently the kit contains a four-bay pouch for the tubes as this was readily available, but Alpha is developing a two-bay pouch that will be more ideal for our particular kit. Based on our positive experience we have already recommended Alpha Labs to another genomics laboratory, for their NHSE ctDNA service. Although their BCK is different to ours, Alpha Labs has provided an alternative solution designed for their requirements. We hope that in future this service will be available on the NHSE supply chain. This will be very beneficial when Marsden360 moves to business-as-usual, enabling hospitals to easily order ready to use sample collection and transport kits, directly from Alpha Labs.” The Alpha Solutions kit is competitively priced, offers multiple time saving benefits, saves time, we can track the orders, and it saves space not having to stock the kits on site. www.alphalabs.co.uk © 2025 Copyright Alpha Laboratories Ltd. 11
Innovating Allergy Testing with BÜHLMANN Flow CAST® Insights from Southampton’s Basophil Activation Testing Journey Kathryn Challis, Senior Clinical Scientist, University Hospital Southampton NHSFT Basophil Activation Testing (BAT) is redefining allergy diagnostics, offeringprecisionand safety in identifying allergens. TheworkatUniversityHospital Southampton with the BÜHLMANN Flow CAST® assay is setting new standards and has become a cornerstone in the diagnostic toolkit used there. Senior Clinical Scientist Kathryn Challis, who oversees BAT services at Southampton, shared insights into their journey, successes, and the vital role of the FLOW Cast in advancing allergy testing. The BAT Journey at Southampton “The BAT service at Southampton was first investigated in October 2019, primarily focusing on perioperative anaphylaxis—a life-threatening allergic reaction that can occur during surgery. Our journey with BAT was driven by the need to better understand and manage severe allergic reactions during surgery. Perioperative anaphylaxis is triggered mainly by anaesthetic drugs used during surgery which can have devastating consequences [1]. The team uses BAT to pinpoint potential allergens, narrowing down the options for drug challenges and preventing unnecessary risks. Collaboration is Key Anaesthetists help us focus on the most likely allergens, and together we work towards finding safe alternatives for patients. This synergy has proven highly effective in managing complex cases, ensuring safe and informed clinical decisions. Today, the centre processes referrals from 15 hospitals, specialising in identifying allergies to anaesthetic drugs like rocuronium, cisatracurium, and atracurium. BÜHLMANN Flow CAST BAT is an in vitro diagnostic method designed to evaluate basophil activation in response to specific allergens. The BÜHLMANN Flow CAST assay uses flow cytometry to identify allergens by analysing the activation of basophils via the IgE-mediated pathway. Our immunology department has an advanced flow cytometer already set up and running, featuring the BD FACSLyric™ analyser, which made adopting Flow CAST a seamless process. Flow cytometry is routine in our lab, so implementing this assay was a natural fit. We can process samples and deliver results within 24 hours. This quick turnaround has been a gamechanger, particularly compared to traditional specific IgE testing, which can take up to four weeks. This rapid response is critical, especially for perioperative cases, as these patients 12 Leading Edge
are often awaiting essential surgeries like kidney transplants or cancer surgery. The quicker we are able to identify the causative allergen, the quicker they can get back into surgery to continue their treatment. However, the manual pipetting involved and the limited capacity to test many suspected allergens at once remain challenges. Despite these, the team has established protocols to ensure high efficiency, including a structured approach to selecting allergens for testing.” Southampton Findings: Perioperative Allergy Testing Kathryn Challis presented her findings at BSI-CIPN inDecember 2024. “In regard to our positivity rate, our most common allergen has been rocuronium which has been positive 7 times so far. We test our drugs using the skin prick testing concentration (sometimes this is too strong), then also dilute 1:10, 1:100, 1:1000 (the BÜHLMANN recommended levels are covered in these dilutions), and have found these patients have always been positive at 1:10, with some patients also positive at 1:100 and 1:1000. We’ve had 21 positive results so far out of 68 patients tested. Detailed case studies have demonstrated the assay’s capacity to prevent high-risk drug challenges and identify safer alternatives. In one case, a 64-year-old female patient experienced anaphylaxis during surgery. BAT testing identified teicoplanin as the allergen, enabling the team to refine her treatment plan and avoid future reactions” The following charts show results from another case: Figure A: Rocuronium Figure B: Cisatracurium Rocuronium (A) and Cisatracurium (B) were tested in a 1:10 dilution. Basophil activation was seen in Figure A, confirming an allergy to rocuronium. This allowed rocuronium to be excluded as an anaesthetic option for the patient. Figure B showed no activation, suggesting cisatracurium as a safe alternative which was then confirmed using the gold standard drug challenge. The Future of BAT at Southampton “While drug-related allergies dominate BAT testing at Southampton, the scope is broadening. The immunology team has begun using BAT for complex cases, such as food allergies, including peanut testing for their paediatric department. Looking ahead the hospital aims to expand BAT applications, including testing for venom allergies (also available from BÜHLMANN) and investigating reactions in dialysis patients. One of the team’s goals is to validate the method further and investigate external quality assurance (EQA) schemes or sample exchanges so we can attain UKAS accreditation. The success of the BAT service has been a real teameffort, from the consultants who initiated this work to the immunologists and anaesthetists who collaborate with us daily.” As BAT testing continues to evolve, Southampton’s innovative use of BÜHLMANN Flow CAST underscores the potential of combining cutting-edge technology with clinical expertise to transform allergy diagnostics. Find out more about BÜHLMANN Flow CAST at: www.alphalabs.co.uk/cast From left to right: Dr Louise Young (Consultant Anaesthetist), Ms Kathryn Challis (Senior Clinical Scientist), & Dr Karen Smith-Baker (Consultant Clinical Scientist) References: [1] https://pmc.ncbi.nlm.nih.gov/articles/PMC7807982/#:~:text=Perioperative%20 anaphylaxis%20usually%20occurs%20within,relation%20to%20the%20drugs%20administered. From left to right: Dr Linda Nel (Consultant Anaesthetist) and Dr Efrem Eren (Consultant Immunologist and Director of the Clinical Immunology Laboratory) Read more on Basophil Activation Testing, scan the code to view the brochure www.alphalabs.co.uk © 2025 Copyright Alpha Laboratories Ltd. 13
Urinalysis by dipstick testing began in the 1950s with the invention of Clinistix by Miles Laboratories1. Glucose and protein tests were developed first, followed by ketones, haemoglobin, bilirubin, urobilinogen, nitrite, leucocytes, pH and specific gravity (Fig. 2). Since the 1960s, these multi-test strips (Fig. 3) have changed little in appearance, with only minor innovations in impregnation techniques, colour indicator stability, and colour gradation2. A study by Crolla et al.3 highlighted that the accuracy of urinalysis depends upon the integrity of the test strips used. False results and diagnoses can arise from degradation of test strip reagents through humidity, agnostic to brand. Simerville et al.4 noted that “False-positive and false-negative results are not unusual in dipstick urinalysis”. Moreover, errors can arise due to human factors such as incomplete dipping (Fig. 4), imprecise read time, and uncontrolled documentation of results. Indeed, Bacârea5 highlighted that “It has been shown that urine samples are not properly collected in more than half of cases…especially in elderly patients”. It is time now for urinalysis to move forward and become standardised, controlled, automated, and digitised. UTS™ - A Paradigm Shift in Urinalysis Urinalysis is used in every care setting, and billions of tests are conducted globally. Given that modern healthcare demands are putting extreme strain on healthcare systems and that there are over 2.8 billion urinalysis tests conducted annually6, improvements inurinalysis canmakea significant improvement in clinical efficiency and patient care. By removing the intrinsic problems associated with traditional dipsticks (whether read manually or by an electronic apparatus), and by automating analysis and reporting, the Urine Testing System (UTS™; Fig. 1) from Clinical Design Technologies provides this paradigm shift. UTS allows point-of-care urinalysis with laboratoryquality accuracy and reproducibility, with test results automatically uploaded onto the electronic patient record. Observing Current Urinalysis Practices We conducted a 3-day observation of urinalysis practices within a Urology Centre to understand how current practices can be improved upon by implementation of the UTS. This study provides a snapshot of current methods and highlights the potential benefits of the Urine Testing System™ (UTS). The parameters evaluated included dip time, read time, total processing time, transcription accuracy, and documentation security. Improper handling (inadequate blotting, and contact with contaminated surfaces) and inconsistent dip times (1–9 seconds) contributed to unreliable results. Reflecting previously described errors, observed average times were often The Evolution of Urinalysis: From Dipsticks to Digital Solutions Nicholas Parham, Senior Product Manager, Alpha Laboratories Ltd. Figure 3 - Multistix Figure 2 - Urine test strip Figure 1 - UTSTM Figure 4 - Dipping COMING THIS SPRING 14 Leading Edge
outside of manufacturer-recommended intervals, potentially affecting test accuracy. HCPs showed inconsistent timing for reagent readings, with readings taken at random intervals (6–187 seconds), often missing the specified timeframes for each reagent. Interpretation of colour results was highly subjective, leading to variability and potential inaccuracies. Overall processing time of 40–293 seconds indicated both out-of-specification testing and inefficient processing of tests. Furthermore, distractions during the manual process further increased risk of errors, and surface cleaning protocols were minimal. These challenges in processing of urine tests highlighted several opportunities for improvement through use of the semi-automated UTS. These included: 9 Timing and Protocol Consistency: Standardised testing intervals to increase accuracy. 9 Objective Result Interpretation: Remove subjectivity through consistent digital interpretation. 9 Enhanced Productivity: Standardised processes can improve productivity and support reproducible outcomes. 9 Resource Optimisation: A streamlined testing protocol can reduce unnecessary repeat tests and lab referrals. 9 Improved Infection Control: Minimise contamination risks through a closed urine testing system. 9 Flexible Testing Locations: Testing near the patient can reduce sample handling time and prevent sample confusion. 9 Minimised Transcription Errors: Digital recording can secure accurate result recording of all tests. Further benefits of using digital urinalysis with the UTS include: 9 Connectivity and Traceability: Digital devices allow realtime visibility of test results across patient touchpoints and align with Electronic Health Records (EHR) for data accuracy. 9 Standardised testing: Laboratory-standard test results are produced using the UTS at the point of care and are consistent across all clinical settings. 9 Data Trend Analysis: Consistent data capture enables insights into individual patient trends and broader health demographics, supporting research and care quality. 9 Comprehensive Record Keeping: Digitally recorded results, including patient/HCP identifiers, ensure quality control and traceability. 9 Reduced Litigation Risk: Enhanced record-keeping reduces risks associated with undocumented or misplaced diagnostic results. A Future-Ready Approach to Urinalysis In conclusion, adopting the digital UTS solution represents a transformative step towards addressing the persistent challenges of dipstick urinalysis, whether interpreted manually or digitally. Common pitfalls such as improper handling, inconsistent dip times, subjective interpretation, and inefficient processes have long undermined diagnostic References: 1. The Development of Diagnostic Test Strips. Commemorative booklet produced by the National Historic Chemical Landmarks program of the American Chemical Society, 2010. https://www.acs. org/education/whatischemistry/landmarks/diagnosticteststrips.html#:~:text=A%20Miles%20 Laboratories%20research%20team,for%20proteins%20and%20other%20substances. 2. https://en.wikipedia.org/wiki/Urine_test_strip#History; accessed 21/01/2025 3. Crolla L, Jimenez C, Patel P. Evaluation of an automated humidity check for instrument-read urinalysis strips. https://www.mlo-online.com/home/article/13004210/evaluation-of-anautomated-humidity-check-for-instrument-read-urinalysis-strips 4. Simerville JA, Maxted WC, Pahira JJ. Urinalysis: a comprehensive review. Am Fam Physician. 2005 Mar 15;71(6):1153-62. Erratum in: Am Fam Physician. 2006 Oct 1;74(7):1096. PMID: 15791892. 5. Bacârea A, Fekete GL, Grigorescu BL, Bacârea VC. Discrepancy in results between dipstick urinalysis and urine sediment microscopy. Exp Ther Med. 2021 May;21(5):538. doi: 10.3892/ etm.2021.9971. Epub 2021 Mar 23. PMID: 33815611; PMCID: PMC8014952. 6. Siemens Healthcare & Global Market Insights Report, 2023. https://www.gminsights.com/ industry-analysis/urinalysis-market accuracy and healthcare efficiency. UTS not only eliminates these issues but also delivers tangible benefits of enhanced accuracy, reduced HCP workload, and seamless integration of reliable data into patient care pathways. These advantages translate into streamlined workflows, improved patient outcomes, and a future-ready approach to healthcare. Reflecting on the challenges outlined in this report, how does your organisation approach dipstick testing? We invite you to share your experiences and explore how UTS can revolutionise your testing processes, enhancing both efficiency and patient management. Share your experience and register your interest in UTS™ at www.alphalabs.co.uk/contact www.alphalabs.co.uk © 2025 Copyright Alpha Laboratories Ltd. 15
Liquid-Stable Quality Controls Introducing new FIT workflow improvements… Coming soon to a lab near you! Kayleigh Roberts & Alexander Ure – FIT Product Managers, Alpha Laboratories Alpha Laboratories is excited to announce a game-changing advancement in quality control solutions with the imminent launch of liquid-stable QCs for use with the HM-JACKarc faecal occult blood analyser from Canon Medical Diagnostics Ltd. (Formerly Minaris Medical Co. Ltd.). This innovative new product is set to revolutionise the way your lab manages FIT workflows. Streamlined, Efficient, and Reliable The new liquid controls come in convenient, easy-to-store packs, containing: 2 x 3ml High concentration dropper bottles 2 x 3ml Low concentration dropper bottles 1 x Control range sheet 1 x Instructions For Use (IFU) Unlike traditional lyophilised formulations, these ready-to-use liquid controls will eliminate the timeconsuming reconstitution process. This means no more aliquot handling and pipetting, allowing for quicker preparation and a more consistent workflow. Minimised Variability and Enhanced Accuracy Reconstitution of the lyophilised quality controls is a pre-analytical variable which can be affected by multiple factors including changes in operator and liquid handling performance of supporting consumables. With liquidstable controls, the reconstitution step is completely removed, ensuring more consistent and repeatable results in every run. This innovation significantly removes these pre-analytical variables, delivering improved accuracy with every test. Save Space and Time Labs will no longer need to create and store aliquots in the freezer following reconstitution as our new liquid controls can be stored in the fridge (between 2 C and 8 C), with a shelf life of For more information about FIT please visit: faecal-immunochemical-test.co.uk 12 months from the date of manufacture. Notably, once a vial is opened, the shelf life remains unaffected, maintaining optimal stability whilst keeping waste to a minimum. Consistent and Reliable Results Our liquid controls have been designed and manufactured to deliver precise, dependable results with minimal deviation. With an assigned value range of ±8% for high concentration and ±10% for low concentration, measurements will be consistent and accurate ensuring that your lab consistently delivers reliable results with every test. 16 Leading Edge
17 Visit The New And Improved FIT Site In response to the growing interest in Faecal Immunochemical Testing from patients, along with resources and bespoke FIT services for Healthcare Professionals, we have redesigned our popular website at www.faecal-immunochemical-test.co.uk Î New dedicated patient area Î Targeted content for healthcare professionals and patients Î Fresh layout design Î Easy to navigate pages Î Improved optimisation for mobile View the new website today at www.faecal-immunochemical-test.co.uk www.alphalabs.co.uk © 2025 Copyright Alpha Laboratories Ltd. 17
Addressing the Challenges in the Diagnosis of Invasive Aspergillosis Nicholas Parham, Senior Product Manager, Alpha Laboratories Ltd Invasive fungal disease is a significant cause of morbidity and mortality, with invasive Aspergillosis (IA) being one of the most common infections. Early diagnosis and treatment are critical to reducing mortality and improving patient outcomes, especially in the critically ill. The population at risk of IA is increasing due to increased transplantation, use of immunosuppression, immunomodulatory therapies, increasing cancer rates, ICU treatment, and severe viral and bacterial respiratory tract infections. However, accurate and timely diagnosis is challenging because conventional methods lack sensitivity, specificity, or are complicated and time-consuming to process. Limitations of Conventional Methods Microscopy and culture are insensitive, or become positive later in infection; they are also often not concurrently positive and can lead to undiagnosed infections. Histopathology is often only available at autopsy, and enzyme immunoassays and PCR are time-consumingandonly available in specialist laboratories. Moreover, test performance can be dependent upon the host’s underlying condition, the specific fungal manifestation, the specimen type, and use of antifungal therapy. This absence of rapid, accurate, and accessible fungal diagnostics often results in empiric utilisation of systemic antifungals, or delayed specific treatment of invasive fungal infection. The Role of Screening and Combining Testing Modalities Fortunately, IA is rare and, even in very high-risk patients, rarely exceeds 15%. As such, diagnostic tests are best used as a screening tool to exclude disease, reducing the need for empirical antifungal therapy. Many of the currently available tests can be used in this way as they have high sensitivity, giving excellent negative predictive value. However, combination of testing modalities, with appropriate sample types, may also afford rapid, early diagnosis with high positive predictive value. This approach can also provide even greater certainty to disease rule-out by further increasing negative predictive value. This can be achieved by combining rapid lateral flow antigen tests with molecular (e.g. PCR) tests. The most valuable in vitro diagnostics (IVDs) for the diagnosis of IA are Galactomannan antigen tests, ß-D-Glucan (BDG) antigen tests, and real-time PCR assays. For Galactomannan, ELISA assays afford high throughput screening and the economy of scale, but require the purchase and maintenance of additional equipment. (i.e. plate reader, microplate washer, fully automated system). However, batch testing of samples is often required to achieve cost-effective use of ELISA assays, which significantly delays diagnosis. Additionally, many smaller hospitals do not have automated ELISA platforms and cannot run these assays efficiently, if at all, and rely on sending samples to Reference Laboratories. Rapid Testing for Informed Decision-Making Lateral flow assays, such as the IMMY sõna Aspergillus GM LFA, provide the ability to rapidly test samples as they arrive at the laboratory. Batching is not required and test time is 45 minutes, as opposed to 3.5 hours for ELISA. BDG testing can also be achieved through the FujiFilm Wako Beta-Glucan Test (90 mins) and PCR with IMMY MDx’s AspID (90 minutes post nucleic acid extraction), allowing rapid reporting of results and informed patient management decisions. Choosing the Right Sample Type Another consideration for rapid and efficient patient management is the choice of sample type for testing. Clearly, bronchoalveolar lavage (BAL) samples that test positive for GM are the most specific for lung infection, and positive blood (serum/plasma) samples indicate disseminated disease. However, BAL is difficult to collect, highly invasive, requires 18 Leading Edge
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