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Portable Laser-Based Scanning Device Detects Critical Biomarkers

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Researchers at the University of Arkansas for Medical Sciences (UAMS) reported advancements to the previously developed Cytophone device. In the current work, the researchers integrated a miniature multispectral laser diode array, time-color coding, and high-speed, time-resolved signal processing into the instrument, which is a photoacoustic device originally designed for early detection of cancer cells,

Described in 2019, Cytophone uses laser beams and sound waves to noninvasively scan circulating blood for melanoma cells, and completes scans of a person’s entire blood volume in a matter of hours. According to findings published in 2019, Cytophone was shown to be about 1000× more sensitive than existing technologies used to detect circulating cancer cells.

The latest version of the device uses the newly integrated features to provide greater portability and specificity than the original patented platform. The multispectral laser diodes encompass wavelengths ranging from 630 to 1650 nm. The time-color-coding mode enables multicolor, in vivo flow cytometry of multiple targets.
Scientific Reports recently published the research findings of co-authors Vladimir Zharov (right) and James Y. Suen (left). The researchers published advances in Cytophone, a noninvasive, miniature, laser-based blood scanner for disease identification. Courtesy of the University of Arkansas for Medical Sciences.
Scientific Reports recently published the research findings of co-authors Vladimir Zharov (right) and James Y. Suen. The researchers published advancements to the device called Cytophone, a noninvasive, miniature, laser-based blood scanner for disease identification. Courtesy of the University of Arkansas for Medical Sciences.
To identify abnormal cells circulating through the body, the multicolor laser diode array is directed at veins or arteries near the wrist. The abnormal cells absorb the light, generating acoustic waves that are detected with small ultrasound transducers attached to the skin.

The researchers used two-color (808 nm/915 nm) laser diodes to demonstrate spectral identification of white and red blood clots, melanoma cells with melanin, and malaria with hemozoin nanocrystals as biomarkers. Using confocal photothermal and fluorescent microscopy, they identified infected cells from a malaria murine model and a cultured human malaria parasite in vitro within 4 h after parasite invasion.

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In the recent study, the platform enabled the researchers to detect malaria — though data obtained in earlier tests, as well as in previously published results using conventional lasers, indicated that the Cytophone platform could be used for the label-free diagnosis of melanoma, blood disorders, stroke, and other diseases. The device overcomes the limitations of conventional lasers, particularly the use of photoacoustic flow cytometry with solid lasers.

“Our latest findings demonstrate that a highly accurate portable device is achievable, which is especially significant for resource-poor countries fighting diseases like malaria,” Zharov said. “This was made possible by exciting breakthroughs in laser diode and digital technologies for counting the acoustic signals from individual biomarkers at different wavelengths for identification of diseases with different spectral fingerprints.”

The results could encourage interest in collaborating with the team on the development and application of the portable device for disease detection, the researchers said.

“Someday, we believe this technology with small, cost-effective lasers will translate to a wearable device the size of a smartwatch or bracelet,” said professor James Y. Suen

“More work needs to be done, but the progress in laser diodes with color numbers higher than in the natural rainbow spectrum make this a promising technology for the identification of different malaria strains,” said Sunil Parikh, M.D., and associate professor of epidemiology at Yale University.

Suen and Zharov established the spinoff company, CytoAstra LLC, through BioVentures LLC at UAMS, to commercialize the patented Cytophone platform initially for detection of circulating melanoma cells.

The research was published in Scientific Reports (www.doi.org/10.1038/s41598-022-11452-w). Previous research was published in in Science Translational Medicine (www.doi.org/10.1126/scitranslmed.aat5857).

Published: July 2022
Glossary
optoacoustic
Optoacoustic, or photoacoustic, refers to a phenomenon and related techniques that involve the generation of acoustic waves in a material induced by the absorption of light. The term "optoacoustic" combines "opto-" (related to light) and "acoustic" (related to sound), reflecting the dual nature of this phenomenon. In optoacoustic imaging, a pulsed laser is typically used to irradiate a sample with short laser pulses. When the laser light is absorbed by the sample, it leads to rapid heating...
flow cytometry
Flow cytometry is a powerful technique used in biology and medicine for the quantitative analysis of the physical and chemical characteristics of cells and particles suspended in a fluid. The method allows for the rapid measurement of multiple parameters simultaneously on a cell-by-cell basis. It is widely used in various fields, including immunology, microbiology, hematology, and cancer research. Here are the key components and features of flow cytometry: Sample preparation: Cells or...
photoacoustic
Photoacoustic refers to the generation of acoustic (sound) waves following the absorption of light (usually laser pulses) by a material. This phenomenon occurs when light energy is absorbed by a material, leading to localized heating and subsequent thermal expansion, which generates pressure waves (sound waves) that can be detected using ultrasonic sensors. The photoacoustic effect is utilized in various scientific and medical applications, including: Photoacoustic imaging (PAI): A...
photoacoustic imaging
Abbreviated PAI. An imaging modality with a hybrid technique based on the acoustic detection of optical absorption from endogenous chromophores or exogenous contrast agents. Light is absorbed by the chromophores and converted into transient heating, and through thermoelastic expansion there is a resulting emission of ultrasonic waves. In tissue, ultrasound scatters less than light, therefore PAI generates high-resolution images in the diffusive and optical ballistic regimes compared to purely...
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