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Monitor What’s Happening Inside Your Cells in Real Time

The inside of a cell, featuring A4Cell's microchip.
Credit: A4Cell.
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Cell lines are used widely across life science research fields from stem cell research and molecular biology studies to drug discovery.

They provide scientists with the opportunity to test novel compounds, learn more about complex biological processes at the molecular level and are even utilized as therapeutics themselves in cell therapy. But not knowing what’s happening inside of cells, in real time, can bring about challenges that limit their utility, particularly in the context of early mechanism of action studies in early drug discovery. It’s a challenge that A4Cell is helping researchers overcome with its proprietary technology, the SPAchip®.

The SPAchip technology consists of intracellular silicon microchips to monitor cellular pathways in real time, over long periods of time, without affecting cell health. The chips are easily internalized by living cells and are printed with multiple fluorescent probes that capture even the subtlest change in a cell’s physiology.

At ELRIG’s Research and Innovation 2024 event, Technology Networks had the pleasure of speaking with Irene González, key account manager at A4cell, and Julio Martín, senior strategic liaison at A4cell, to learn more about the SPAchip technology and lab-in-a-cell devices, and why the applications of the technology are “limitless”.

Molly Campbell (MC): Can you talk to us about the core challenges that exist in single-cell analysis studies, within the context of drug discovery?

Irene González (IG): Monitoring what's happening in your cell models in real time – whether it’s a 2D cell culture, a single one or a complex cell model like organoids – presents limitations. Live-cell imaging in drug discovery and cell biology research is hampered by drawbacks of traditional fluorescent chemical probes in solution, such as cytotoxicity over time, difficulty of multiplexing, expelling of molecular from cell and poor cell penetration.

MC: Can you discuss how your product portfolio is helping to address these challenges?

IG: A4cell develops and commercializes detection kits for your cells based on our SPAchip technology. These chips are microchips that have probes attached to them, and once they get inside of cells, you can track different parameters in real time. It’s like having a tiny lab inside of your cells or having an eye inside your living cell as a sentinel supervising what is going on.

MC: Can you talk about the type of research that is being done using the SPAchip technology?

IG: Based on this particular platform, we have a pH detection kit and a calcium detection kit, both of which are single detection kits. We have also launched a multiplexed platform, which combines multiple probes on the same chip; so, using one single reagent, you can monitor different parameters at the same time in the same experiment. We are also developing new applications such as an oxygen detection kit and a reactive oxygen species (ROS) detection kit.

We recently completed a proof-of-concept study using the technology in spheroids. They work, the signal is stable and you can monitor your models for long periods of time, which is great when you are working with these precious samples that can take weeks to grow. Moreover, the chips remain inside the cell, resisting spheroid loss during handling such as cell disaggregation.

Currently, we work mainly with industry partners that are in the early drug discovery process or cell biology research. Our technology fits in with the cell-based assays methodologies and is also being used by groups that are looking at new technologies to make their processes more efficient. One specific case study is the use of our technology in toxicology and mechanism of action experiments. With SPAchip technology, you can see how the pH levels or calcium levels change when different drug concentrations are applied in different cell lines. 

Julio Martín (JM): Another field of application might be cell suppliers, particularly stem cells suppliers. We think that monitoring the health of the cell throughout the production and scale-up processes could add a lot of value here as QC indicator. It’s like having a sentinel inside of your cells – you can label a specific percentage of your cells and monitor what is happening across them. Once the chip is inside a cell, the cell does not have any mechanism to remove it, which allows you to track the cell forever, effectively, as long as it is alive. 

I often think about possible applications of our technology outside of the life sciences, in spaces such as environmental detection, diagnostics or even therapeutics. The potential is enormous. The SPAchips can be used as cellular cargo vessels for a variety of molecules and particles. You can attach not only molecular probes, but also proteins, oligonucleotides and microbes. We are open to hearing about opportunities and ideas on how partners might want to use our probes.

MC: Do you think that the SPAchip technology could be applied in cell painting?

IG: Cell painting consists of morphological multiplexed-labeling using dyes that require fixation and staining; thus, it provides a highly informative output at end-point snapshots. SPAchip technology helps to enlarge the cell imaging studio by enabling physiological cell filming, since monitoring is harmless and real-time. We envisage that cell biology researchers will find both methodologies complementary within their experimental toolbox.

MC: What is the greatest challenge that you face as a start-up company?

IG: I would say a lack of resources is a big challenge. Start-up companies are typically extremely limited in numbers, so we have to multitask, and we have to pick the right conferences to attend. We would love to exhibit in all the conferences, but it is just not possible as a start-up.

JM: We also need to have a sense of the problems that our users – our target customers – have. We need feedback. We are a technology provider, and so we rely on insights from our target customers to understand how we can help to solve their problems. Events and conferences are very important for us, as they provide an opportunity for us to interact directly with individuals that can provide us with relevant feedback. I think that, across technology-based companies, we need to be able to progress from technology to applying that technology to specific applications that provide unique solutions to a specific problem. For A4cell, our field of application is cell biology – it’s a universe, it’s infinite. So, it is a challenge, because the potential applications are vast.

About the interviewees:

Irene González is a key account manager at A4cell. Julio Martín is a senior strategic liaison at A4cell. A4cell's vision is to offer powerful and innovative tools to academia, pharma and biotech industries for monitoring and enhancing long-term live single-cell analysis studies in cell biology research and drug discovery and development.