For centuries, malaria has been one of the deadliest diseases on the planet. Nearly half of the world remains at risk of malaria with more than half a million deaths each year, most of them in children. While some progress has been made in controlling malaria and developing a vaccine, this has stalled recently, with a growing number of deaths since 2019. At the heart of the challenge is the lack of non-invasive and rapid diagnostic technologies for malaria, which are urgently needed, especially in remote or low-resource areas with limited healthcare infrastructure. Happily, a new frontier in medical technology is offering hope, in the form of the Cytophone, a revolutionary device that can detect malaria through the skin without drawing a single drop of blood. This innovation, developed by a team led by Prof. Vladimir Zharov at the University of Arkansas for Medical Sciences and licensed to Cytoastra for further commercialization, represents a leap forward not just in malaria diagnostics, but in how we might monitor disease altogether. More
Cytophone is based on a combination of four discoveries: the photoacoustic effect, circulating tumor cells (or CTCs for short), lasers, and flow cytometry. The photoacoustic effect, discovered by Alexander Graham Bell in 1880, involves the transformation of light into sound. Thomas Ashworth first observed CTCs in a cancer patient’s blood in 1869. The first laser was developed by Theodore Neiman in 1960. In vivo flow cytometry, using a laser-induced photothermal and photoacoustic effect for the detection of CTCs directly in the blood flow, was first explored by Vladimir Zharov in 2004. Alexander Graham Bell also developed a photoacoustic wireless telephone, called a photophone, to “hear” sunlight-induced sound from a film, while Zharov’s Cytophone “listens” to a laser-induced sound from single cells in blood.
The roots of this versatile technology lie in cancer research, specifically the detection of CTCs in patients with melanoma. In a landmark 2019 study, Prof. Zharov and his collaborators demonstrated the Cytophone’s ability to noninvasively detect melanoma-derived CTCs traveling in the bloodstream. Melanoma, the deadliest form of skin cancer, often spreads through the circulation before symptoms appear. Traditional methods of detecting these rogue free-floating cancer cells are invasive, often unreliable, and unable to catch the disease early.
The Cytophone shines laser pulses through the intact skin to identify CTCs in the blood flowing through an underlying blood vessel, based on their melanin content. The laser light causes local melanin heating, accompanied by thermal expansion and results in sound wave emission, allowing it to “listen” to CTCs with an acoustic sensor. The results were extraordinary: the Cytophone detected CTCs with a sensitivity more than 1,000 times better than existing assays, down to a few CTCs in whole blood, all without needing to draw blood.
Once this groundbreaking melanoma study validated the Cytophone as a platform for in vivo “liquid biopsies” without a needle, the researchers realized that they could adapt the Cytophone technology for other diseases where identifying disease-generated specific circulating cells or particles is critical, including in infectious diseases such as malaria.
Diagnosis of malaria, caused by Plasmodium parasites transmitted through mosquito bites, currently relies on either microscopic examination, rapid diagnostic tests, or PCR assays, all of which require blood samples, specialized tools, and experienced operators. These methods are often unreliable at low parasite levels, and they may also not be readily available for people living in remote or low-resource areas where malaria can often be a major problem.
Zharov’s team adapted the Cytophone to detect hemozoin, a crystalline pigment produced by malaria parasites as they digest hemoglobin in infected red blood cells. Like melanin, hemozoin absorbs laser light and generates acoustic waves that can be detected through the skin.
The result is a malaria-specific version of the Cytophone that uses harmless laser and acoustic sensor arrays gently attached to the skin’s surface to “listen” to what’s happening in the bloodstream during an infection. In a clinical study conducted in Cameroon, one of Africa’s malaria hotspots, in collaboration with Prof. Sunil Parikh from the Yale School of Public health and Prof. Yap Boom from the University of Yaoundé and Doctors Without Borders, the device accurately and with high sensitivity detected malaria in patients and tracked infection progression and drug efficiency over time, all without needles or laboratory work.
Strikingly, the device sometimes picked up signs of malaria infection when other tests did not, potentially detecting residual hemozoin from earlier infections or very low levels of parasites that escaped conventional diagnostics.
What makes the Cytophone so powerful is its versatility. In the earlier melanoma study, the same core technology not only detected CTCs in real time but also physically destroyed some of them by generating vapor nanobubbles around the heated melanin nanoparticles and their clusters, a potential future avenue for combining diagnostics and therapeutics, where a disease is diagnosed and treated almost simultaneously. This opens up tantalizing possibilities: could the same principle one day be used to neutralize malaria parasites in infected cells? Could it detect and treat other disease markers or participants, such as sickle cells or circulating blood clots?
Prof. Zharov believes the answer is yes. An ongoing clinical trial is investigating the detection of circulating blood clots in stroke patients in the U.S, while clinical testing of infected children was recently completed in Burkina-Faso with support from the Bill Gates foundation. Zharov’s vision is of a future where a portable Cytophone device can be deployed anywhere, by health workers in rural villages, clinicians in urban hospitals, or potentially even by individuals in their own homes, or deliverable in ambulances or helicopters.
Although the Cytophone remains a clinical prototype, its potential is enormous. The biomedical engineering and regulatory team is currently developing a commercial grade Cytophone design making it affordable, with rapid (one minute or less) and automatic identification and counting of disease-associated circulating markers and the ability to function with hand motion and skin pigmentation. Further optimizing Cytophone to distinguish between different pathogens and diseases and testing its performance in wider populations, will enhance its future impact on healthcare.
If successful, the Cytophone could become not just an essential diagnostic tool to help with the eradication of malaria, but a universal platform for detecting and managing a wide range of diseases, including cancer, infections, and blood disorders, quickly, painlessly, and in real time.
Digital health technologies such as smartwatches have demonstrated significant progress in monitoring standard medical parameters such as pulse rate, temperature, blood pressure, oxygenation and others. However, the extension of this technology to cancer, infections, and other critical medical conditions using wearable blood sensors is still in its infancy. This gap could be filled by a small battery-based Cytophone using tiny laser diodes to warn of a risk of stroke, metastasis, or pathogen invasion.
It’s a happy moment when one innovation shows such promise across multiple medical frontiers. But the Cytophone, born from a deep understanding of light, sound, and biology, and how they can work together, could be that breakthrough. Thanks to the pioneering work of Prof. Vladimir Zharov and his team, the dream of painless, rapid, needle-free diagnostics might soon be a reality.
