Diagnostics for the Real World: point-of-care diagnosis made easy

By Catherine Jewell, Communications Division, WIPO

In an ever more interconnected world, the threat of infectious diseases is perhaps greater today than at any other point in human history. Controlling and preventing these diseases is a huge challenge – particularly in resource-poor regions of the world – and one that requires early detection. A ground-breaking new point-of-care diagnostic tool, developed by Dr. Helen Lee and her group at Diagnostics for the Real World, offers healthcare workers in resource-poor environments an opportunity to effectively test, diagnose and treat patients within hours. Dr. Lee, who also established the Diagnostics Development Unit at University of Cambridge in the United Kingdom, tells us more about the remarkable device and shares her views on innovation and intellectual property.

How did you become an inventor?

I really became an inventor through necessity. My goal has always been to develop diagnostics that are simple, accurate, rapid, heat-stable and inexpensive for resource-poor settings. Invention starts with a need, that’s what drives it forward. To be successful, one needs to be able to deal with failures, day in and day out: to bounce back and never give up.

I am also quite curious and was lucky enough to have parents who never put a ceiling on what I could do. Their response was always, “why not?” So I have had no ceiling to stop me and I always try to find a way.

What prompted you to move from the industry to academia?

My husband and I have an agreement. One time I move for his career and the next time he moves for mine. When I went to Abbott Laboratories, he left a very good job to follow me and then when he was offered a professorship at Cambridge, I followed him. I learned a lot and gained a great deal of valuable experience at Abbott, but the corporate world was not for me in the long run.

Tell us about Diagnostics for the Real World?

We set up the company as a spin-off from the Diagnostics Development Unit at the University of Cambridge in 2003 where a lot of the fundamental research was done. We are still scaling up our operations and now employ 40 people. We are for profit, but profits are capped at 15 percent for low- and middle-low income countries, and our motto is “balancing doing well with doing good”. I was determined to set up a company and scale up production and distribution. As I often say to my group, if all we do is publish a few papers in high-impact journals and develop a prototype, we will have failed. We are delighted to have secured a rather substantial order recently from The Global Fund. It’s our biggest yet. So it’s been all hands on deck.

What is it that you make?

We have developed a simple and robust way to detect infectious diseases at the point of care in resource-poor settings. It’s built around nucleic acid testing which not only enables earlier detection of infectious organisms such as HIV but can also monitor the effectiveness of its treatment. Conventional nucleic acid testing requires highly trained personnel and sophisticated laboratory facilities in order to extract, amplify and detect the targeted nucleic acids. It is a complex process that can be very difficult to carry out in a resource-poor setting. We set about simplifying that process and making it more user-friendly and robust. And we succeeded. Our device, the SAMBA II – our engineers like dancing! – is the size of a small domestic coffee machine and converts the detection of nucleic acid into a simple visual signal like a pregnancy test: two lines, it’s positive; one line, negative; and no line, it’s incorrect. This simplification of an extremely complex process took years of research and won the 2016 Inventor of the Year Award by the European Patent Office.

SAMBA is operated by a tablet which allows data to be transmitted easily to the relevant health authorities. It also uses long-lasting thermostable paper for printout, if needed. It took us almost 10 years to develop our latest, more user-friendly SAMBA II machine and chemistry. The SAMBA test comes with unit dose cartridges (containing some 180 required chemicals and reagents) which are simply inserted into the machine. The cartridges are uniquely shaped and, like LEGO blocks, they can only be inserted one way, the correct way. SAMBA works on the principle of sample-in, results-out, and aims to be foolproof.

With the realities of resource-poor settings as our starting point, we have really tried to ensure that all elements of the instrument are robust, stable and heat tolerant. SAMBA II can operate in temperatures up to 38°C. We also invented a process to stabilize labile enzymes to ensure our reagents withstand high temperatures – up to 37°C – for around nine months. To achieve this, we did something unconventional: we eliminated certain standard chemicals. This included getting rid of one that produces cyanide, which has turned out to be a tremendous advantage from the point of view of the environment and waste disposal.

The kit includes everything needed to collect a sample, even gloves. Sample collection and extraction is like the wheels of a car, without them you go nowhere. I am convinced it is the key to early detection and successful treatment of infectious diseases. We are delighted that SAMBA is now being used in regional and district hospitals as well as lower level clinics in the Central African Republic, Malawi, Uganda and Zimbabwe. We are also carrying out in-country trials in Cameroon and Nigeria, to be shortly expanded to Tanzania.

What else makes the SAMBA II stand out?

From the outset we had the realities of resource-poor settings in mind and made our mistakes early in the development process, thanks to funding from organizations such as the Wellcome Trust, the National Institutes of Health (NIH), the Children’s Investment Fund Foundation (CIFF) and, more recently, UNITAID. Many of the diagnostics available today are made for Western markets and cannot be adapted easily to many clinics in resource-poor settings where power cuts are a daily occurrence. The SAMBA machine provides an uninterruptible power supply that kicks in when needed, so the test can be completed if there is a power cut.

Surprisingly, dust was our biggest unforeseen problem. When you do nucleic acid amplification chemistry, you need an airflow to cool the device. That means dust gets in everywhere. We overcame the problem by redesigning the filter holder and making it easy to remove. We now use a washable air filter.  

We believe the SAMBA II HIV test is a real game-changer because by being adapted to whole blood samples, it eliminates the need for both phlebotomists to collect blood samples and a centrifuge to prepare plasma for testing. Both of these are in short supply in resource-poor settings. All SAMBA II needs is a droplet of blood from a finger prick to be placed in a vial and inserted into the machine which will then detect the presence (or absence) of infection.

Can the SAMBA II be used elsewhere?

Yes, there are many potential uses – in old peoples’ homes to detect and prevent the spread of flu, at airports to test quarantined fruits and on farms for bovine TB testing. It’s a new tool that opens up new uses and hopefully new markets.

What role does intellectual property play in your company?

I firmly believe in the importance of patent protection, and for a small company we have invested a great deal in it. We hold 17 patent families all related to diagnostics and have registered SAMBA as a trademark. We also protect our technologies by filing international patent applications under the Patent Cooperation Treaty. This system allows us to defer the cost of filing patent applications in national territories and can provide valuable feedback about the patentability of our inventions before we make the decision to proceed in those territories. 

IP rights help us defend our interests against its unauthorized use and give us the freedom to operate. That is everything. A large company recently tried to revoke one of SAMBA’s key patents related to an inventive, yet simple sample extraction method for nucleic acid testing without generating cyanide which is a common by-product of conventional extraction methods. Thankfully this attempt was unsuccessful in that our patent was upheld with only minor amendment, although an appeal of that decision by the large company is pending. I figure we must be on to something good if they are tracking us and trying to invalidate our patent!

Now that we have regulatory approval, and our first big order, I am determined to make the company profitable. Only then can we be sustainable. We are committed to scaling up our operations, maintaining the quality of our product and generating enough income (thanks to our intellectual property (IP) rights) to continue improving and developing new applications for our technology. It’s all really exciting and exhausting!

What sort of impact is the SAMBA having?

I recently visited a small clinic in Kenya, and was quite moved to learn that thanks to their use of our SAMBA II for early infant diagnosis, for the first time, the physicians were able to test a baby on the spot and treat it without waiting weeks or months for the results. Centralized testing has an uneven impact because of difficulties in transport, communications and in recalling patients. Testing and treating patients immediately can significantly improve health outcomes. And with the SAMBA test, physicians can also show their patients via the visual signal that their treatment is working, which motivates them to stay with it.

Where would you like to be in 10 years?

We are looking to see where SAMBA can make the greatest impact, both as a business, and in terms of improving health outcomes. Our aim is to diagnose and treat millions of people over the next decade. I really would like to see our simple and effective devices being used everywhere, but we need to be smart and strategic as we go forward. It’s a lot of fun and I am dying to see where and how far we can go. 

What can governments do to support small companies in their use of IP?

I would like to see some kind of fund set up to help small companies defend their IP rights during the “valley of death”, where the technology has been developed but scale-up and commercialization are needed. Any company benefitting from the fund would, in return, agree to pay a percentage of revenues generated from future sales or licensing. That way the fund becomes self-perpetuating. Had such a fund existed, we would have been able to sue a large diagnostics player for infringing one of our key patents. Unless all companies can protect their IP rights, they only benefit from one side of the IP coin. We still have freedom to operate – it’s true – but unchallenged infringement actions undercut potential economic returns for small companies. This is fundamentally wrong and should be countered.

How do you explain the gender gap in innovation?

Innovation and the patents that protect it are gender indifferent. Women are of course as capable as men in deciding which experiments to do, and are often natural inventors. The gender gap in innovation is an upstream problem. There are simply not enough women in senior or leadership positions. Although there are lots of fantastic women out there, it can be difficult for them to maintain their career through their childbearing years. Without a flexible working environment, women will not be able to bear children and have a career without struggle – it just won’t happen. That is why it is so important for employers to offer more flexible working arrangements and for our social services to provide excellent but affordable child-care. This is not about women’s lib; it is about capturing women’s talents and ensuring that society benefits from them. 

As a member of the jury for the 2018 Inventors Award by the European Patent Office, I am very happy to see that this year’s award had record-breaking number of winners who are women. This truly demonstrates that women inventors have arrived in spades by their achievements.

Why is innovation important?

Innovation is critically important because it improves our lives on so many different levels. If exploited properly, it can remove inequality between sexes, nations and peoples. And it’s fun.

What advice do you have for girls and young women?

My mother always told me, “If you really want to do something, and if what you want to do is really worthwhile, the world will stand back and let you go through.”

Who is your greatest inspiration?

My mother, of course, and a certain Dr. Rosemary Biggs, who told me something very simple. She said, “Helen, be useful.” I have never forgotten that. And I like being useful.