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Enzyme-Linked Immunosorbent Assay (ELISA) is a cornerstone technique in immunology for detecting and quantifying various substances such as peptides, proteins, antibodies, and hormones.
While manual execution of ELISA assays is still common in many research and diagnostic labs, it is prone to human error, leading to inconsistent results.
This blog post discusses frequent mistakes made during manual ELISA assays and highlights how automation can mitigate these issues.
Preparation errors
Inaccurate mixing of reagents and pipetting and cross-contamination
Manually executing critical tasks like reagent mixing and pipetting leaves assays open to mistakes, inaccuracies and inconsistencies from the beginning.
For example, improper mixing of reagents can lead to uneven distribution, while manual pipetting often results in inconsistent volumes. Cross-contamination between wells can also occur due to poor pipetting practices or splashing.
These kinds of pipetting errors affect assay sensitivity and specificity, increase waste and associated costs, and compromise repeatability, while executing manual tasks like this is the leading cause of repetitive strain injuries in the lab
Pipetting is one of the easiest, most cost-effective processes to automate, and as such, is one of the first to be switched from manual to automated.
Read our complete guide to automated pipetting for more information about choosing an automated system and going beyond pipetting to automating full liquid handling processes or even entire workflows end-to-end.
Automated full liquid handling systems speed up the movement of small and precise volumes of liquids and can be programmed to set protocols for aliquoting, mixing, and serial dilution of liquid samples. Compared to their traditional manual counterparts, they increase efficiency, productivity, and cost savings while supporting the delivery of highly accurate and repeatable assay results without researcher-to-researcher variability.
Timing challenges
Inconsistent incubation and reagent addition times
Timing is crucial in ELISA assays because each step — coating, blocking, washing, incubation with samples and detection antibodies, and substrate reaction — requires precise durations to ensure optimal binding and reaction conditions.
Small, often undetectable inconsistencies in incubation start and stop times, reagent addition and even plate-washing processes can result in variations in antigen-antibody binding and enzymatic reactions.
Automating ELISA allows every process step to be controlled, with systems adhering to strictly prescribed incubation parameters and actions for uniform timing across all samples.
And while automating these processes removes manual errors and strain injuries, it also frees scientists from the frustration of closely monitoring assays.
Throughput and productivity restrictions
Too much scientist dead time
ELISA systems can be restricted by incubation time requirements, washing and immunostaining requirements, and shift availability.
Automated ELISA systems don’t necessarily work faster than a person, but they allow machines to be tended to concurrently and enable complete hands-off time as the system can run independently of human interactions.
Because of this, automation is an excellent way for labs to increase productivity and reliably and flexibly scale throughput.
Data inaccuracy problems
Reproducibility, misinterpretation and validation consequences
Manual data recording within any setting is prone to transcription errors, and given their sensitivity and specificity, maintaining the integrity of the data throughout the ELISA process is paramount.
Consequences of inaccurate data recording in ELISA include:
Misinterpretation of results
Incorrectly recorded data can lead to the wrong conclusions about the presence or concentration of a target molecule, affecting downstream applications, such as diagnosing diseases, evaluating vaccine efficacy, or conducting basic research.
Reduced reproducibility
If data is inaccurately recorded, other researchers or even the original team may struggle to replicate the findings, undermining the study’s credibility.
Compromised quality control
ELISA assays often include controls to ensure they are working correctly. Inaccurate recording of control data can obscure issues with the assay, such as reagent problems or procedural errors, leading to erroneous results being accepted as valid.
Erroneous statistical analysis
Statistical analysis relies on accurate data input. Incorrect data can skew statistical results, leading to false positives or negatives and ultimately flawed scientific conclusions.
Wasted resources
Inaccurate data recording can necessitate repeating experiments, leading to unnecessary consumption of resources and time.
Regulatory and compliance issues
Accurate data recording is often a requirement for regulatory compliance, especially in clinical settings. Inaccurate records can result in regulatory non-compliance, potentially leading to legal consequences and loss of certification or accreditation.
Automated LIMS
Companies are already implementing Lab Information Management Systems (LIMS) alongside automated laboratory machinery to revolutionise workflows and reduce the potential for data errors.
The LINQ Cloud software bridges the physical and digital aspects of automated ELISA on our lab automation platform, LINQ. It integrates with all the instruments in use, transferring data to any LIMS in real-time without manual transcription. This enables labs to produce high-quality, reproducible data sets for contextualisation, standardisation, collaboration, and easier validation.
How can automation help with ELISA validation?
Validation is a crucial part of the ELISA process and is required to ensure the workflow’s precision, accuracy, and reproducibility. It assures users and regulators that assay results are consistent and reliable.
Automated ELISA platforms can help validation with precision, standardisation, speed and efficiency, throughput, data collection and analysis, and compliance with regulatory requirements. Read more about ELISA validation and automation here.
Conclusion
While manual execution of ELISA assays is common, it is fraught with potential errors that can compromise results. Automation offers a robust solution to these issues, enhancing accuracy, consistency, and efficiency in ELISA assays. By integrating automation into your laboratory workflow, you can significantly improve the reliability of your results, ultimately advancing the quality of your research and diagnostic capabilities.
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The dawn of lab automation has brought with it many efficiencies. From increasing walkaway time for scientists to increasing throughput in response to demand, life in the lab has become easier to plan, predict and optimise.The key to this lies in creating a platform that delivers both robotically and digitally, connects instruments, streamlines data flows, and supports dynamic lab scheduling at both a hardware and software level.
Efficient experiment scheduling software offers a multitude of benefits, from ensuring time, instruments and people are being used to their full potential, to improving reliability, consistency and experiment success rates.
However, finding a scheduler that can assign tasks to a set of heterogeneous resources with efficiency in mind, taking into account both the constraints of each resource and responding to these parameters if they change in order to deliver a complete workflow, is a whole new challenge.
Why are schedulers important?
Experiment scheduling software helps streamline processes and workflows in the lab.
They can:
Support the creation of new and unique workflows and protocols
Help analyse performance, optimising instruments and workflows
Allow virtual workflow simulations for testing timing and experiment design
Facilitate the execution and tracking of multiple workflows when instruments, robots and transport systems are fully integrated
Most labs have moved on from simply tracking experiments on paper or with spreadsheets, and we now see two popular types of schedulers in use: static, and dynamic. Their algorithms are typically either rule-based, considering specific scheduling problems or goals, or mathematical optimisation algorithms that seek to minimise end-to-end workflow execution time.
Static schedulers
Static schedulers make decisions based on known constraints. They typically allocate tasks before execution starts, and they do not have the functionality to change this during the run time in response to information from task-tracking events.
How a static scheduler may handle an instrument error during a run
Benefits and drawbacks of static schedulers
Because known parameters are used, static schedulers are good for simple predictable processes, are robust when the data in use is accurate, and don’t involve multiple threads being created, synchronised and working in parallel. While this may reduce risk, time efficiencies in generalised applications may be lost.
The predictability offered by static schedulers can help labs with resource allocation, dictating who needs to be available to monitor or support the workflow, what instruments will be available for other uses, and when results can be expected.
The main disadvantage, like with lots of lab automation solutions, is that experiments often don’t follow simple routes and rules, with each variable representing a potential issue that could cause the workflow to pause, delay or fail completely. Fault tolerance is low, load balancing is difficult, and adaptability is limited with static scheduling.
Dynamic schedulers
Dynamic schedulers adapt their decisions based on information provided during runtime. They take into account information from multiple real-time events and allocate resources based on real-time status and workload information.
How a dynamic scheduler may handle time constraints during a run
Benefits and drawbacks of dynamic schedulers
This built-in adaptability reduces the risk of workflow failure as the scheduler seeks to find an alternative route to successful execution.
Dynamic schedulers can reassign tasks that are failed or delayed without waiting for a master node or operator to intervene, improving reliability, removing the need for manual monitoring, and providing detailed data for use in experiment design and instrument optimisation.
Due to its complexity, dynamic scheduling requires sophisticated programming and can increase initial set-up times, with multiple threads needing to be created and synchronised. Moreover, losing the ability to pre-plan executions for optimality can limit experiment throughput or introduce variables that impact the consistency and quality of results.
Dynamic replanning schedulers
Our LINQ Cloud scheduler takes the benefits of static and dynamic schedulers and offers users the best of both worlds.
It has the ability to consider known constraints for effective workflow planning and resource allocation while using state-of-the-art solving algorithms to keep workflow delivery on track.
LINQ Cloud’s dynamic replanner scheduling engine considers:
Time constraints
Known conditionals
Data transfer events
…allowing time to completion and expected results to be predicted while facilitating:
Batch parallelisation
Real-time error handling
Dynamic rerouting
Deadlock prevention
…enabling full confidence in successful workflow completion.
How LINQ Cloud’s scheduler handles run errors and constraints
Why LINQ Cloud and dynamic replanning scheduling
Our scheduler concentrates on allowing labs to maximise their instrumentation while reducing reliance on scarce resources like people to benefit the workflow and, ultimately, its results.
By taking the best bits of static and dynamic schedulers, and combining that with our workflow builder software, we’ve been able to develop something that’s easy to use, makes an impact immediately, and supports labs on their journey to automation adoption.
We have created a scheduler that outperforms across applications featuring explicit constraints handling and multi-assay workcells. By combining static solving with dynamic response capabilities, more labs will be able to automate and reap the benefits of reliable automated workflow execution.
Daniel Siden, Director of Product, Automata
Interested in learning more about the benefits that dynamic replanning scheduling can bring to your lab?
Speak with one of our automation experts today
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We’ve never been in a more socially and environmentally aware world. And that puts businesses under immense pressure. Pressure to do good, share success, deliver on promises, and to publicly state their position on all sorts of things – from sustainability to community impact. And many already do.
Sustainability reporting isn’t new; Corporate Social Responsibility (CSR) or Environmental, Social and Governance (ESG) has been around for some time (and is now mandatory for some companies regulated by the Non-Financial Reporting Directive (NFRD)), but for those who really want to showcase their commitment to good, there’s B Corp certification.
If you’ve heard of B Corps but don’t know what they are, have a vague idea but want to know more, or are just looking for inspiration for future sustainability goals – keep reading.
What is a B Corp/what is a Certified B Corporation?
B Corps are those companies that place social and environmental impact as high on their priority list as financial profitability.
Those dedicated to meeting the highest standards of social and environmental performance possible can apply for certification from B Lab (a global non-profit focused on shifting the balance from capitalism, to a system that addresses society’s most critical challenges while benefiting everyone) who then track relevant ESG metrics and hold the certified accountable.
Certified B Corporations are businesses that meet the highest standards of verified social and environmental performance, public transparency, and legal accountability to balance profit and purpose. B Corps are accelerating a global culture shift to redefine success in business and build a more inclusive and sustainable economy. - B Lab
As of August 2022, there are 5,424 certified B Corporations across 156 industries in 84 countries.
How do you become B Corp certified?
Anyone across the world can apply for B Corp certification, but achieving it takes much more than just disclosing non-financial information and pledging to ‘do good’.
There is an extensive assessment stage, in which questions about everything from governances to workers, community, customers, suppliers, environment, and financials will be asked, evidenced, analysed, scrutinised
At the final stage of certification, B Corps are legally required to consider the impact of their decisions on all of their stakeholders by integrating stakeholder governance into the company’s governing documents.
Stakeholder governance looks to move prioritisation away from profits – which they would be under shareholder governance – to ensuring the interest of all stakeholders is what drives decision making. Stakeholders here means everyone and everything affected by company activities: customers, workers, suppliers, communities, investors, and the environment.
Put simply: stakeholder governance ensures we have better businesses that are accountable to people and planet. - B Lab
In jurisdictions where other corporate governance legal frameworks are in place, B Lab advocates for companies to adopt stakeholder governance commitments within company constitutions, articles of incorporation, and other formation documents, in order to embed the same structures that feature in benefit corporation laws.
Being a Certified B Corporation isn’t the same as being a benefit corporation
If you’ve heard the term ‘benefit corporation’, don’t get confused.
A benefit corporation is a type of corporate governance recognised in some states of the US.
It sprang out of the B Corp movement and their purposes overlap (consideration of impact beyond just shareholders but to wider stakeholders), but they’re not the same.
Famous B Corps
Many household names hold B Corp certification.
There are over 700 in the UK across all sectors and sizes, including Riverford Organic Farmers, Divine Chocolate, Big Issue Group, EQ Investors Group Ltd, Danone, Gousto, Zen Internet, Guardia Media Group, Apro and Octopus Group.
Why think about becoming B Corp certified?
As leaders in the movement for economic system change, B Corps reap remarkable benefits.
They build trust with consumers, communities, and suppliers; attract and retain employees; and draw mission-aligned investors.
As they are required to undergo the verification process every three years – and they’re expected to increase their score in that time to prove they’re progressing towards becoming an ever more equitable, inclusive, and regenerative business – B Corps are by definition also focused on continuous improvement, leading to long-term resiliency.
Where to start?
If you need help with setting up effective record keeping in preparation for certification or to explore sustainability reporting further, get in touch with our business advice team who can help get you started.
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With lab space almost zero in some life science-intensive regions of the UK, fast-scaling organisations need to explore alternatives to increasing lab size. Is automation the key? Let’s explore.
The future of life sciences hangs in the balance. Not because of funding or ambition, but because of space.
Putting scientific innovation at the heart of growth plans has meant that companies especially in the UK are seeking to double or even triple output in many areas, from genomics to synthetic biology. However, there isn’t enough room for fast-scaling organisations to expand lab operations, so a new approach is needed.
No space in the Golden Triangle
Particularly around established and academically rich locations in the UK, available lab space is almost zero.
Consequently, big life sciences names operating in this Cambridge-Oxford-London ‘Golden Triangle’ find themselves constrained, with no space for expansion.
In Cambridge, lab supply is still below 0.5% and requirements are now topping a million sq. ft.Bidwells Office and Labs Market Databook
Even locations designated Life Sciences Opportunity Zones – Stevenage, Birmingham, Harwell in Oxford, Cambridge, Wiltshire, and Kent – are space-poor, with some still being in that overcrowded Golden Triangle region.
This lack of space in concentrated biotech and life sciences regions impacts start-up and scale-up businesses seeking knowledge-rich, collaborative areas to move into, as well as established players needing to grow.
Three options for finding more lab space
Moving
There are of course many other countries in the world with equally as impressive life sciences institutions that don’t have similar space constraints. Boston, for example, has millions of square feet of lab space immediately available to tempt investors away (9.9% of space was available as of March 2023).
That being said, UK government investment in life sciences is generous, our academic profile is second to none, and breaking into or relocating to another market isn’t possible or desired by some businesses.
Being in certain territories or regions also has benefits that would be lost in relocation. European pharma giant AstraZeneca was chosen as the preferred partner for the University of Oxford Jenner Institutes COVID-19 vaccine project over the US-based Merck & Co., for example.
Waiting
For those looking to stay, there is new space being developed but competition for that will be rife. For most, though, the time to respond to increased demand is now.
Bidwells report a total of 370,000 square feet of space expected to be completed in 2023 and a more sustained supply pipeline for 2024 but that won’t meet demand.
Some office buildings are being repurposed into lab space, and it’ll be crucial for those facilities to be flexible. Any lab created now must be ready to change as quickly as tomorrow.
Open, integrated automation (OIA) solutions will help.
Rethinking
OIA involves robotically and digitally connecting multiple devices. It looks outside of individual instruments and instead tackles the challenges holding labs back, building solutions that address them completely to truly unlock the potential of workspaces and the people within them.
LINQ is our first OIA solution for life science laboratories.
Our ambition is that automation not only protects newly established labs from becoming obsolete or inflexible too soon, but that it removes the need for scale-up relocation altogether.
LINQ combines a truly innovative lab bench that is modular, with flexible dual-purpose layers; software that makes workflow automation programming quick and easy; and world-class service that is there to help you redefine your automation at the drop of a hat.
Just a few of the ways LINQ can be configured
The impact of space-saving automation
We helped one lab increase its genomic testing capacity to go from 16,000 to 50,000 samples a day, with no additional staff.
The lab was also limited by space restrictions, and existing workflows involved disparate pieces of equipment and the manual transfer of samples and data from one workstation to another.
As well as wanting a solution that could grow and develop as their needs evolved, the lab required fast implementation with little downtime and a solution that required only training.
After implementing LINQ in the customers’ lab, throughput was increased with staffing hours decreased, manual handling and associated errors were reduced, and data quality was improved.
See what our solution looked like
Adapt or be left behind
With demand increasing, a skills gap growing, and technological advancements rapid, re-evaluating how you approach automation is crucial for future success and lab growth.
Speak to Team Automata to see how LINQ can help you unlock your lab space today. Our next showcase event will be SLAS Europe this May!
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HMRC has launched a serious campaign to try and tackle abuse of its systems across the board, with more fraud investigators being recruited, spot checks increasing, and an extra £510m from the government to fund the efforts.
The R&D tax relief – or R&D tax credit – system is not immune from these increased measures. Just this month advisors have received notice of increased claim turnaround times to accommodate for extra compliance checks being undertaken and it shows no signs of slowing.
As a result, new claimants are feeling more nervous than ever about using the R&D tax relief scheme, while existing ones are treading with an extra sense of caution.
The dreaded ‘HMRC enquiry’ has been part of claiming R&D tax relief for years, but as these are increasing we thought we should revisit what they are, when they happen, and what you can do about them to alleviate some of the fear.
What is an HMRC enquiry, or HMRC compliance check?
Firstly, they’re the same thing. Compliance check is more modern terminology, but HMRC enquiry can also be used. (Note: HMRC inquiry is a US English spelling and occasionally use in British English dependent on formality. Here, we'll use compliance check, or enquiry.)
It’s exactly what it sounds like – HMRC doing a double check on the compliance surrounding your R&D tax relief claim.
In practice, this means requesting more information about a claim in order to determine whether it’s genuine, and with the rules of the system.
If any of these look unusual, if things don’t match up, or if more details are needed, an enquiry – or compliance check – can be raised by the inspector.
This isn’t automatically negative; HMRC isn’t looking to penalise genuine claimants, but to monitor the system to ensure genuine companies undertaking qualifying activities receive the rewards they deserve; and that those who aren’t genuine, aren’t.
Here are a few reasons a claim may be flagged:
Your claim value has significantly increased
The R&D you’re undertaking is new for/to your sector
Occasionally HMRC will look at your claim as a benchmark for future, similar claims in the sector if the R&D isn’t something they’ve come across before.
Lack of evidence
Financial inconsistencies
The above two are really the same thing: does what you’re saying make sense, can you evidence it, and have you calculated things correctly.
Claims including subcontractors and EPWs are often flagged for compliance checks if the amount claimed against them is high.
Similarly, claiming against projects that have also had grant funding increases your chances of an enquiry being raised.
Random spot check
What happens when a check is raised? How do I know if my claim is being checked?
You’ll receive a letter saying that HMRC are conducing a compliance check of your R&D tax relief claim; this is the start of an enquiry.
It’ll probably be headed ‘Check of the Company tax return for the period ended…’, and will include a list if questions that you need to answer.
You should act on this immediately. You typically have 30 days from the date on the letter to respond but it could take some time to gather the answer to the questions, and, if you’ve claimed through an advisor, you need to take their turnaround times into account too.
The first step after this is to return your answers, along with supporting evidence if needed; these will be reviewed, and either more questions will come, or your answers will suffice to close the enquiry. It's also useful to make contact with the inspector on your case to discuss timelines and build a relationship.
If further questioning takes place, this can be done via a meeting (face to face or online, restrictions dependent), where a tax inspector and occasionally a technical colleague will interrogate your claim and ask you to respond.
If you don't agree with the outcome you can appeal the decision and ask for another chance to state your case, or you can accept the conclusion.
The longer you take to answer questions, the less helpful your responses are, and what decision you decide to accept will all impact how long the process will take.
What happens when a check is raised? How do I know if my claim is being checked?
You’ll receive a letter saying that HMRC are conducing a compliance check of your R&D tax relief claim; this is the start of an enquiry.
It’ll probably be headed ‘Check of the Company tax return for the period ended…’, and will include a list if questions that you need to answer.
You should act on this immediately. You typically have 30 days from the date on the letter to respond but it could take some time to gather the answer to the questions, and, if you’ve claimed through an advisor, you need to take their turnaround times into account too.
The first step after this is to return your answers, along with supporting evidence if needed; these will be reviewed, and either more questions will come, or your answers will suffice to close the enquiry. It's also useful to make contact with the inspector on your case to discuss timelines and build a relationship.
If further questioning takes place, this can be done via a meeting (face to face or online, restrictions dependent), where a tax inspector and occasionally a technical colleague will interrogate your claim and ask you to respond.
If you don't agree with the outcome you can appeal the decision and ask for another chance to state your case, or you can accept the conclusion.
The longer you take to answer questions, the less helpful your responses are, and what decision you decide to accept will all impact how long the process will take.
I’ve received a letter checking my eligibility to claim; is this a compliance check notification?
No. These letters – sometimes called ‘nudge’ letters – are designed to remind claimants that they should ensure their eligibility before claiming tax reliefs.
This type of letter will contain a heading such as ‘Research and Development (R&D) tax relief – help confirming you are eligible’.
Following the guidelines on the letter is all you or your advisor need to do – this involves reviewing your claim again to make sure you’re satisfied that everything stated within it is accurate and can be evidenced, correcting it and resubmitting if not.
What are the possible outcomes of a compliance check?
Delays to your payout
Your payment will definitely be delayed if it’s flagged for a compliance check. Pay out times in the best circumstances have been increase to 40 days recently, so anyone under enquiry will face an even longer turnaround than that.
Successful defence
Many advisors have excellent defence success rates. That’s one of the reasons our clients work with us. The ultimate goal of any defence against a genuine claim is to maintain the claim value and win the maximum relief for the client.
Even if you’re not a client but you need support with a compliance check, we’re happy to help. Get in touch.
Reduced claim size
If activity is found to be ineligible or costs can’t be evidenced, those parts of the claim can be rejected, meaning you’ll receive less than you initially applied for.
More checks against historical claims
HMRC has the right to review filed claims dating back six years, and even further if deliberate fraud is suspected.
If those checks fail, historic claim values can be reduced – meaning you’ll have to pay back funds newly determined as incorrectly received, regardless of whether you’ve already spent them.
Reputational damage
Unfortunately, once you’ve been flagged for one compliance check you may now be on HMRC's radar, and future checks could be more likely.
Investigation/audit
On occasion, checks/enquiries do escalate to full-scale investigation or audit. This is serious. HMRC will check financial activity against your business thoroughly, looking to uncover any and all errors to determine full compliance in all areas – not just in your R&D tax claims.
Penalties
HMRC does have the power to issue penalties (financial or prison sentences) to fraudulent claimants, and we’re seeing more stories of this happening. Fortunately, however, this is reserved for deliberate criminal activity and uncooperative plaintiffs.
If errors are found to have been deliberately made, or information is seen to have been intentionally hidden, penalties of up to 100% of the tax lost by the Exchequer, plus interest, can be issued.
Who is held responsible if a claim is rejected - me or my advisor?
You!
An advisor will provide support based on professional experience and knowledge, but you are ultimately responsible for giving them honest and accurate information, and checking that their interpretation of your R&D and financials is right.
It's incredibly important you work with a reputable advisor that you can trust, and one that knows your sector. For help understanding what 'good advice' looks like, check out our free guide here.
How can I avoid an HMRC compliance check?
You can’t. Even if your claim is 100% accurate, evidenced, explained and triple checked, spot checks still happen!
What you can do, however, is ensure what you are filing is as solid as it can possibly be.
This is one of the key reasons companies use an R&D tax relief adviser like MPA. We have in-house tax advisors, accountants, and technical experts who will work on your claim together to ensure as best as we possibly can that what we file on your behalf is compliant and clear.
That means checking financials, interrogating cost breakdowns, applying the right tax law to your unique situation, filing through the right scheme, uncovering all activity and excluding that which won’t stand up to scrutiny, and, of course, defending you should an enquiry be raised as part of your agreed fee.
You have final sign off on your claim and it's you who is liable should issues be found, so building a good relationship with a reputable advisor is crucial.
Where can I go if I’m facing one and I don’t have an advisor/my advisor can’t help?
Many R&D tax advisers including MPA offer HMRC enquiry defence as an additional service to new clients, as well as including it as standard for existing.
To speak to MPA about your compliance check leave your details here and we’ll see if we can help.
If seeking external help isn’t right for you, we encourage you to use the information included in your initial letter which will provide extensive guidance, and before you submit, check out our content section for all the help you need on filing a robust R&D tax relief claim.