It was of course a buzz to hear that the revolutionary system we call CellPreserve was an Innovation Award finalist at the SLAS 2021 Science Ignited global conference. But what’s more rewarding? The fact that the liquid biopsy innovation created alongside brilliant colleagues here at Cambridge Consultants could go on to make a real difference to patient outcomes where early diagnosis is paramount.

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The idea for CellPreserve was sparked by a desire to make liquid biopsies – sampling and analysing non-solid biological tissue, usually blood – more effective and meaningful. They’re much less invasive than tissue biopsies, which is good news for patients. But the drawbacks include the fact that, at early stages of cancer and other diseases, you may only manage to isolate a handful of affected cells, or even just a single cell, from the blood. 

Those rare cells are the key to identifying both the disease and its best possible cure. But once outside the body, the cells usually have a very short lifespan – three to four days at best – which means the clock is ticking in terms of experimentation and analysis.  

This set me to thinking. Is there any way of incubating the rare cells that would extend their life? This would be a significant breakthrough. A longer cell lifespan would allow for more research to be carried out, enabling the biopsy to be more meaningful and informed. Today, the future of treatment, especially cancer, is to tailor it to the individual patient and to the individual disease. The more we can find out about these rare cells, the better the outcome for the patient. 

The usual practice is to isolate a rare cell in a solution of glucose to keep it alive. However, the cell’s usual metabolic processes will mean that all the oxygen and glucose in the solution will soon be depleted. The rising levels of waste product (primarily carbon dioxide) mean that the cell is in a solution with rising levels of acidity. The cell will start to die. 

Affordable and scalable 

Over the past nine months, I have worked with a team of engineers, biologists and developers here at Cambridge Consultants on a new way of incubating rare cells. The aim is to nurture the cells outside the body so that they live far longer and – importantly – to find a way of doing so that is affordable and scalable. I’m not working on a piece of academic research. The aim is to create a practical system which can be used inexpensively in medical labs. 

My idea is based around the use of an ordinary printed circuit board (PCB) measuring around 2.5cm square. On this, a single cell can be held in a ten nanolitre droplet of glucose solution. The electronics of the circuit board allow the droplet to be moved around the board and to be manipulated in various ways, extending its capacity to be the ideal environment for a cell’s survival. In essence, it is a tiny incubator for a cell. 

In this way, we have extended the life of the cell in our CellPreserve device to around 14 days. How does it work? Well, here’s the detail. The circuit board is encased in clear plastic and monitored constantly by a custom made optical system. When the optical system observes that the cell’s droplet solution is showing signs of change, such as rising acidity, lack of oxygen and/or glucose, the electronics in the board spring into action. 

The tiny droplet of solution can be moved electronically across the circuit board to a position where more incubating solution is added, using syringe drivers. This can both rebalance the pH and add nutrients. To ensure the original droplet does not get too large, it can then be pinched in half so that it returns to its original size while containing fresh solution. The other droplet of solution can be analysed if required or discarded. 

Effective prototype device 

This system is called EWOD – Electrowetting on Dielectric – and in our prototype device it is proving very effective. It works as the electrodes on the surface of the chip are turned on and off, causing changes in the surface tension which move the droplet of solution around the board. 

The droplet is held at a steady 37°C to mimic body temperature, which throws up the problem of evaporation. To combat this, there are two ways that CellPreserve can operate. The first is to float a coating of oil around the droplet, to prevent loss of liquid. The other is to surround the cell-containing droplet with sacrificial droplets on adjacent electrodes. These will work together to protect the cell’s environment as they will evaporate first and can easily be topped up. 

Here at Cambridge Consultants, we have a wealth of experience in microfluidic work and in fabrication at cellular level. Our aim in this piece of in-house research was to create a system that is of genuine and affordable practical use to medical labs. So, if pushing the project closer to a commercial product launch is something that interests you, please drop me an email. It would be great to continue the conversation. 

Author
Josh Gibson
Senior Physicist, Physics & Sensors

Josh Gibson (MPhys) is a senior physicist with a passion for developing technologies which pair physics with biology. With a background in optics, microfluidics and data analysis, Josh has prototyped diagnostic hardware, patented process validation equipment for cell therapy manufacture and developed an innovative optical system for DNA analysis.