Meet the triathlete and researcher revolutionising the way we understand feelings, and even our brains

The mental health crisis is rapidly increasing, with nearly 1 in 5 United States adults suffering from a serious mental illness in 2020. Looking deeper, we find that emotional instability and altered neurological behaviours are most common among adults of ages 18–25, though relatively common across all ages, races, and genders. This is largely because mental health has become increasingly stigmatised in recent cultural and socio-political climates, both in the United States and internationally.

Mental health issues are frequently viewed as embarrassing or dramatised, often delaying treatment or health. Most notably, the classical conception of mental health is that of a problem, but not necessarily an actual disorder or health issue.

When we think of depression, anxiety, or bipolar disorder, we think of mood, thinking, and behaviour. These three hallmarks of mental health issues are then associated with treatments such as therapy and medicinal prescriptions as a peripheral stall. Too frequently, mental health is treated as a social or emotional concern and not as a biological one. While therapy and psychological conditioning may be effective, is it feasible that we could address these issues at their root by assessing and treating them neurologically?

In true STEM fashion, researchers have already begun dreaming up experiments to answer this question. I sat down with Dr. Nako Nakatsuka, a senior scientist in the Laboratory of Biosensors and Bioelectronics at ETH Zürich and a recipient of the 2022 MIT Technology Review Under 35 Innovator award, to hear about her sensory solution.

Nakatsuka developed aptamer biosensors that could detect small chemical changes within the brain, and even differentiate between structurally similar chemicals, such as neurotransmitters, agonists, and metabolites. Such chemical changes in brain fluid or tissue can reflect the neurological state of individuals with mental health and brain disorders.

Biosensors

A core aspect of Nakatsuka’s research product was biosensors, or bio-compatible devices capable of detecting an analyte, any substance whose chemical composition is being analysed, such as a molecule or micro-organism. In the following, we’ll break down Dr. Nakatsuka’s biosensor setup into three parts: the receptor, the transducer, and the reader.

The Receptor

Biosensors frequently combine micro-electronic hardware and biochemical materials. The main component of a biosensor, called a receptor, recognises the presence of such analytes and produces a characteristic signal. Natural biology has blessed us with plenty of receptors, such as enzymes, antibodies, cells, and nucleic acids, which naturally have binding affinities to certain chemical signatures. In her biosensor, Nakatsuka uses aptamers as her receptor unit. Aptamers are artificial strands of nucleic acid (RNA or DNA) with extremely low off-target binding. These aptamers act as molecular switches, shape-shifting as they bind to their targets.

The Transducer

After obtaining the bio-recognition event from the aptamer, the signal needs to be transformed into one that can be measured internally and externally (e.g., electrical/analog or digital). The transducer accomplishes this via a process called signalisation, in which an optical—electromagnetic, light-based signal — or electrical signal is proportional to or indicative of the quantity of analyte-bioreceptor interactions produced. Using quartz nanopipettes, Nakatsuka et al’s aptamer-based biosensors were able to transduce shape changes in the presence of a neurotransmitter. In other words, using these tiny pipettes, the aptamers rearrange in the presence of their programmed biomarker. Below is an example of such a nanopipette, made with quartz, then doped with aluminum oxide:

The Reader

Finally, a reader is used to process the signal and display the value such that it is interpretable by the scientists. There are two main steps to this process. The first is signal conditioning, in which the raw analog signal that is transduced is converted into a conditioned signal through a variety of electromechanical and computational steps. Essentially, this conditioned signal is a ‘refined’ version of the original, as it has significantly less noise and is within a signal threshold that is appropriate for processing. 

Following the conditioning, the signal is converted from analog to digital. An analog signal is essentially a continuous function; the types of graphs that you would draw in biology or chemistry, where a time-varying — value, such as a temperature, pressure, or colorimetric change, is plotted concerning time — quantity is represented by a curve. To digitise the signal, this curve is essentially chopped up into little, discontinuous intervals, which are then binarised (converted into 1s and 0s, the fundamental language of computers).

Finally, this binary data is changed back into informational values, such as electrochemical impedance, voltage vs Ag/AgCl, dissipation, frequency, current, and other serotonin-indicative quantities, all of which helped Nakatsuka and team to determine the effectiveness and quality of their solution. Ultimately, it’s this data and methodology that gives their sensing system novelty and utility!

Why?

We began this article by talking about mental health issues, which is one of the most powerful use cases of this technology. Imagine being able to quantitatively understand the neurotransmitter activity occurring in your brain during any given scenario. This would offer immense therapeutic capabilities, both cognitively and chemically. For one, we would surely get better at modulating and exercising our emotions in a physically healthy manner, but it would also allow scientists to see how to interfere with neurochemical activity with high specificity, perhaps to combat neurodegenerative disorders or mental health illnesses (e.g., PTSD).

With similar neuromodulation technologies already proliferating in the scientific scene, such as optogenetics, intracortical brain-computer interfaces, and the like, Nakatsuka’s innovations will also enhance their impact. Neurochemical interactions are fundamental, but minimally understood, so insights from her research could further enable scientists to control and observe interneuronal activity at high fidelity, which remains within the thinly veiled realm of impossibility today. On our call, Dr. Nakatsuka and I also discussed the implications of her work on improving 3-D maps of the brain, such as those of the human connectome project, which primarily looks at the electrical wiring of the brain, as opposed to its chemical interplay.

This being said, Dr. Nakatsuka — being the amazing scientist that she is — acknowledges that there are still limitations to her work and that her publication represents just one rung on the ladder that are the possibilities to come.

About the Author

Hi, my name is Okezue Bell, and I am a social technologist and activist with interests in computer science, applied math, and bioengineering. I run a social and financial equity startup called Fidutam and am heavily engaged in the sustainability industry. Feel free to comment on this article or message me if you have questions, and leave claps if you enjoyed it!

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— Okezue

Credits

I designed, wrote, and edited this article. Thanks so much to Dr. Nakatsuka for being kind enough to meet with me and share her knowledge! (go Japan for the World Cup btw :))

More about biosensors: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4986445/