The Evolution of a QUOD Box

Bespoke, ergonomic and unique to the Quality in Organ Donation (QUOD) biobank, the QUOD sample collection boxes are critical to the transportation of donor blood, urine and tissue collected by nurses and retrieval teams. Sample collections are taken at four different time points across the donor management period, all the way through to the point of organ retrieval.

Manufacture

These custom-made sample collection boxes are assembled by hand and distributed nationally from the Oxford hub by QUOD Technical Assistant, Sophia Ali. Sophia joined the team four years ago and she continues to ensure that the Specialist Nurses in Organ Donation (SNODs) and retrieval teams across the UK are well-stocked with QUOD boxes, as well as other essential resources needed in theatre for sample collection. This can include biopsy punches and other equipment to aid in processing samples in the lab. “The most vital piece of kit which I am responsible for building and supplying across all hospitals in the UK”, she says, “is the famous QUOD box.” Watch a video demonstration of Sophia constructing a QUOD box [here] or read the step-by-step process from Sophia below.

How to build a QUOD box by Sophia Ali

“The QUOD box is made up of several components. You start with the outer box which is initially flat packed. Our vibrant QUOD sticker as well as the receipt and map sticker are applied. At the back of the box, we store the two information sheets, one for Scotland and one for England, Wales, and Northern Ireland along with the consent sticker.”

“Inside the box you will find individual red, green, blue, and yellow foams. Each foam represents a separate component and holds a different sample from the donor. The red foam will hold twelve blood tubes – six EDTA, three Heparin and three SST tubes. All are barcoded to identify the collection at separate time intervals. In the yellow foam you will find the BAL tube, three urine tubes and one (orange top) spleen container filled with RNAlater preservative. The green and blue foams contain the five tissue tubes. In the blue foam, the five tissue tubes are filled with formalin and the green, with RNAlater preservative. We currently collect liver, left kidney (in formalin), right kidney (in RNAlater), ureter, right heart ventricle and left heart ventricle. Each box will contain a worksheet where each sample collection can be recorded, and any variance notes can be added. There will also be DB1 and DB2 collection for blood serum in the preliminary stages of donation. Each box will be labelled with a unique barcode to ensure complete traceability. I also make note of where each box is shipped to via this barcode.”

Shipping

On a typical working day Sophia will respond to e-mail requests from SNODs and regional centres, subsequently building each QUOD box and packaging consumables accordingly, ready for shipping: “Due to demand, I have to make sure I have enough material to fulfil all requests. I aim to complete all requests within two working days”. During her time at QUOD, Sophia has calculated that she has built and distributed approximately 4,250 QUOD boxes since 2019! With the rising cost of consumables in recent years, the cost to produce and ship one QUOD box is currently around £60.00 GBP.

From retrieval to research

Tissue biopsies are stored in two different types of media for transportation to preserve the tissue in the best way possible whilst allowing for the widest variety of techniques to be carried out in future studies. Each sample has a unique identifying barcode which is recorded on the QUOD database to preserve traceability and donor anonymity throughout the whole process. The QUOD database links clinical donor information to these samples, allowing researchers access to samples that meet the requirements of their research.

Evolution

The current design represents years of continual evolution and improvement (as pictured), in accordance with changes to legislation from the early stages of QUOD to today. 2023 marks a ten-year milestone which we have honoured with a new logo that can be seen on each QUOD box.

Sophia remarks how the design is under constant review and has seen major changes in recent years, including changes to tissue collection and corresponding changes to the worksheet. Most recently being the change to kidney biopsies, whereby the biopsy from the left kidney goes into formalin, with the biopsy from the right kidney being preserved in RNAlater. Previously, biopsies from each kidney were divided in two, with each half going into formalin or RNAlater. There have also been changes to the sizes of heart and kidney biopsies over the years, in response to feedback from retrieval teams who collect the samples, researchers who use the samples and results from internal quality assurance audits.

A decade of QUOD marks a time of reflection for the whole team, as we look back on the evolution of the biobank over the last ten years and think about all the people who have helped us reach this landmark. We look forward to celebrating this achievement with our wider QUOD family throughout the year and most especially at our symposium on Friday 8th December 2023 at Exeter College in Oxford.

British Transplantation Society 2023

From QUOD to Scotland: QUOD travelled to Edinburgh for the 50th anniversary of the British Transplantation Society (BTS).

In March, QUOD Research Assistant, Dr Hannah McGivern and Technical Assistant, Sophia Ali journeyed up to Edinburgh for the Joint Congress hosted by the British Transplantation Society (BTS) and NHS Blood and Transplant (NHSBT). This year, delegates were able to celebrate the 50th Anniversary of the BTS and showcase the latest developments in the fields of organ donation and transplantation.

The conference provided a great opportunity to speak with so many of our colleagues from across the QUOD consortium, including Specialist Nurses in Organ Donation (SNODs), retrieval teams, clinicians and researchers, answer questions and listen to feedback.

When asked about her experience after attending her first conference as a representative of QUOD, Sophia commented on how great it was to meet the wider QUOD network: “I communicate with all the SNODs and NORS teams through e-mail, so meeting them in person was lovely. They gave lots of positive feedback about QUOD and how it has been working well over the years in donor hospitals. SNODs enjoy being part of the process and knowing how the work we do day to day can bring forward some ground-breaking research. It was great to speak to the people who handle the QUOD boxes after I have shipped them, to hear what their roles are in QUOD and to listen to them speak about their own personal experiences during the many stages of the QUOD sample collection process. They were also incredibly surprised that each QUOD box that they have handled is built by me!”

QUOD was honoured to be included in the opening keynote lecture on ‘Predicting the Future – Technologies to Inform Organ Utilisation’ delivered by Professor Menna Clatworthy, University of Cambridge. Furthermore, we were delighted to meet with healthcare professionals and researchers who have utilised QUOD samples as part of their research studies that were presented at the congress.

On the final day of the conference, QUOD Principal Investigator, Prof Rutger Ploeg and Basic Science Co-ordinator, Dr Maria Kaisar delivered a presentation as part of the UK Organ Donation and Transplantation (ODT) Research Network session, acknowledging the ten-year accomplishments of the biobank as well as recent collaborations and exciting new developments.

New QUOD Colleague Questionnaire – Dr Ana Gil-Bernabe

Dr Ana Gil-Bernabe – Quality & Governance Manager for QUOD and QUANTUM Biobanks

What were you doing most recently before joining QUOD?

I worked in the Human Tissue Governance group, which is part of RGEA (Research Governance, Ethics and Assurance), within Research Services at the University of Oxford. This was a research support role focused upon ensuring that work with human tissue at the University of Oxford is performed in compliance with the UK legislation and the Human Tissue Licence conditions. Basically, the aim was to allow the progress of science within the legal and ethical boundaries that regulate clinical research.

What interested you about working with QUOD?

During my time in the Human Tissue Governance group, I interacted with the eight biobanks that operate under the main Human Tissue Licence at Oxford, including both QUOD and OTB. This was a great opportunity to understand what a fantastic research resource biobanks are for researchers, here and abroad, and how they optimize their very valuable samples that are donated to the biobanks. QUOD is a fantastic example of national and international collaboration, with samples collected and delivered to multiple sites. I understood that it was a great opportunity to apply my acquired knowledge on human tissue governance and quality assurance, as well as to progress on my knowledge on human tissue biobanks and their governance. Last, but not least, I do have a passion for research (I have been a researcher for about 15 years) and the field of transplantation is very close to my heart.

What does your role in QUOD involve?

In a nutshell, ensure that QUOD adheres to the legal and ethical frameworks that regulate clinical research in the UK, in particular the Human Tissue Act 2004, and to the conditions of the Human Tissue Licence at the University. QUOD Governance is transitioning to a Quality Management System, iPassport, to make this task easier, and part of my role will be to support this transition. We will use iPassport to manage our governance documents, run audits, report non-compliances and keep training records, for example. I will also support compliance with other frameworks that relate to clinical research, such as the Health Research Authority or the Research Ethics Committees.

Lightning round time:

If you were stuck on an island what three things would you bring?

  • Documents, of course, any activity needed would be well described in the relevant Standard Operating Procedures (SOPs);
  • iPassport, of course, all those documents will be accessible through iPassport;
  • Nothing else, I love the sea, so I’d enjoy the opportunity to swim and explore the island.

Where’s your favourite place?

It could well be that island, but probably my hometown, Cadiz, as it not only has a lovely coast, but also all the ingredients for happiness: family, friends, good weather and good food. In its absence, any place near the sea, with the sound of the waves and the smell of the salty water.

Finally, what kinds of enquiries should people bring to you, and how best can they reach you?

Anything to do with governance and quality assurance: documents (SOPs, Risk Assessments, Working Instructions), audits, non-compliances and training records, for example. As we transition to iPassport, I imagine many questions will be related to the use of this system.

You can reach me at ana.gil-bernabe@nds.ox.ac.uk and I’m setting up other ways of communication, using Planner and Teams – more information to come!

QUOD & Evotec: an academia–industry partnership built on complementary strengths

Tobias Bohnenpoll, Evotec SE

Evotec SE and the University of Oxford have recently renewed their collaboration agreement, reflecting a robust and sustainable partnership to profile tissue biopsies collected, processed and stored by the QUOD programme. Through this partnership, Evotec has already generated genome-wide bulk transcriptomic data from about 2,000 donor biopsies (895 kidney and 910 liver), complementing the rich clinical records and technical metadata collected by NHSBT and QUOD. Evotec is currently extending the analysis to heart biopsies and high-resolution single cell and spatial transcriptomics, which will allow in-depth molecular characterisation of tissue microenvironments. Together, we aim to generate mechanistic insights to improve the quality of organ donation and transplantation, and to identify targetable mechanism of injury and repair that will open new avenues for therapeutic intervention and patient stratification in metabolic, cardiac and renal diseases.

The multimodal characterisation of organ biopsies using state-of-the-art, high-throughput analysis is an important cornerstone of Evotec’s Molecular Patient Databases (E.MPD), an industry-leading, proprietary collection of curated human datasets for translational research and patient-centric target and biomarker discovery. However, the integration of complex clinical and molecular data into curated multidimensional datasets poses great challenges to scientific teams and requires interdisciplinary approaches. Evotec and QUOD researchers have assembled an expert team that efficiently combines domain knowledge in medicine and biology with high-throughput molecular analysis and modern data science. Together, we are exploring the complex relationships between biopsy molecular profiles, donor and recipient clinical phenotypes, and graft outcomes in all major organ recovery and transplant conditions. This exploratory analysis of biopsy transcriptomes involves unsupervised clustering, dimensionality reduction and embedding of clinical data and molecular signatures to enable a data-driven hypothesis generation.

Importantly, the multidimensional characterisation of QUOD biopsy transcriptomes has enormous potential beyond research in organ donation and transplantation, with direct applications in modern drug discovery. First, samples from healthy organ donors that are obtained from the Oxford Transplant Biobank (OTB) can serve as reference for the molecular analysis of other disease-focused prospective cohort studies, which often lack appropriate controls. Second, organ donors often present with early, subclinical disease phenotypes that potentially provide unique insights into the onset and early progression of metabolic and other common diseases. For example, Evotec has integrated a data-driven selection of QUOD and NURTuRE (National Unified Renal Translational Research Enterprise) kidney biopsy transcriptomes ranging from healthy to end-stage chronic kidney disease to model disease initiation and progression at the molecular level. We are also combining transcriptomic analysis with AI-assisted digital pathology to characterise liver biopsies for steatosis, inflammation and fibrosis and determine their position along the spectrum of fatty liver disease.

Ultimately, these systems biology approaches aim to positively impact the lives of patients with organ transplantation, cardiometabolic diseases and related complications by leveraging advanced molecular analysis and interdisciplinary expertise. This transformative work is only possible through close collaboration between academia and industry, combining their strengths and resources to achieve meaningful advances in knowledge that will help improve patient care and therapeutic intervention.

Spotlight on a QUOD Colleague – William Murray

This year, QUOD is celebrating its 10-year anniversary and for this edition of the QUOD newsletter, I was delighted to speak with William Murray who has been a Specialist Nurse in Organ Donation (SNOD) for NHSBT since the inception of QUOD back in 2013 in Edinburgh, Scotland. QUOD has now collected over 128,000 samples from more than 7,000 donors, supplying in excess of 38,000 samples to more than 55 research projects. This milestone would have certainly been insurmountable without the extraordinary efforts of this national consortium, including the Specialist Nurses who have such a critical role in the process.

William describes his role as a SNOD for NHS Ayrshire and Arran as multifactorial. He explains how the Specialist Nurses manage the process of organ donation from the point of referring a potential organ donor, working with colleagues in the intensive care units (ICU) and being present in theatre during retrieval. The SNODs are also responsible for the clinical management of the donor to ensure the stability of the patient all the way through the retrieval process through to family after-care. This includes speaking with the families or next of kin of the patient regarding consent/authorisation for research and the collection of samples for the QUOD biobank. William notes that the key to being a SNOD is communication, empathy, forming a rapport with people and using your instinct to judge what is right for every family member going through what is a very difficult time in their lives.

William explains how the respect and dignity to the families’ loved one is upheld and in the foremost thoughts of those involved during the process of obtaining samples for research purposes and that taking biopsies for QUOD does not affect the efficacy of the organs upon transplantation. Sample collection for QUOD closely mirrors the sampling required for the donation process and families are already aware that blood and urine is routinely analysed from patients while in hospital. William notes that the QUOD process works well because it has been built around the systems that already exist in the hospital.

When asked what advice he would give to any nurse or clinician considering specialising in organ donation, he advised to not lose sight of the unique relationship between the relative or next of kin and the patient, that the bond between a couple or parent and child does not change regardless of age and to be mindful of this.

The work that William does for QUOD is in fact a relatively small aspect of his day-to-day routine. He talks about how SNODs spend much of their time on call, covering the region that they work in which can often be a very large geographical spread. For William, this can include the whole region of Scotland! When not on call, William says that his focus is on teaching and raising awareness in addition to clinical audit and policy development. The latter includes identifying potential limitations or barriers to organ donation and working closely with clinical colleagues and committees to design and implement policies that address these barriers.

William remarked that change in his role is almost constant as incremental changes often occur on a weekly basis in reaction to clinical outcomes. William also discussed the interest in supporting organ donation and changes that he observed following the Government Campaign in Scotland, ‘Do Not Leave Your Loved Ones in Doubt’, which urged the public to register their decision with regards to the NHS Organ Donor Register and to speak about their decision with their families.

To close, William observed how being a SNOD is a complex role, helped by technological advancements with more information leading to better outcomes, very hard work but also incredibly rewarding; a unique position which gives him the opportunity to bring about meaningful change far and wide, and yet still work on a local level in the ICU, which is very important to him. He remarked how privileged he felt to work in a role that can help patients and their families across the UK, “What I do in Ayrshire, makes a difference at a national level”. Having started his career as an intensive care nurse, William says that “the intensive care unit is in my bones” and speaks warmly of the camaraderie and community embedded in the ICU and the connection amongst the SNODs.

A special thank you to all the SNODs across the UK, along with all the clinicians, retrieval teams, surgeons and technicians that have enabled QUOD to reach this monumental milestone!

William Murray was interviewed by Hannah McGivern.