Towards rainbow portable Cytophone with laser diodes for global disease diagnostics.

In vivo, Cytophone has demonstrated the capability for the early diagnosis of cancer, infection, and cardiovascular disorders through photoacoustic detection of circulating disease markers directly in the bloodstream with an unprecedented 1,000-fold improvement in sensitivity. Nevertheless, a Cytophone with higher specificity and portability is urgently needed. Here, we introduce a novel Cytophone platform that integrates a miniature multispectral laser diode array, time-color coding, and high-speed time-resolved signal processing. Using two-color (808 nm/915 nm) laser diodes, we demonstrated spectral identification of white and red clots, melanoma cells, and hemozoin in malaria-infected erythrocytes against a blood background and artifacts. Data from a Plasmodium yoelii murine model and cultured human P. falciparum were verified in vitro with confocal photothermal and fluorescent microscopy. With these techniques, we detected infected cells within 4 h after invasion, which makes hemozoin promising as a spectrally selective marker at the earliest stages of malaria progression. Along with the findings from our previous application of Cytophone with conventional lasers for the diagnosis of melanoma, bacteremia, sickle anemia, thrombosis, stroke, and abnormal hemoglobin forms, this current finding suggests the potential for the development of a portable rainbow Cytophone with multispectral laser diodes for the identification of these and other diseases.

Dynamic blood flow phantom with negative and positive photoacoustic contrasts.

In vivo photoacoustic (PA) flow cytometry (PAFC) has great clinical potential for early, noninvasive diagnosis of cancer, infections (e.g., malaria and bacteremia), sickle anemia, and cardiovascular disorders, including stroke prevention through detection of circulating white clots with negative PA contrast. For clinical applications, this diagnostic platform still requires optimization and calibration. We have already demonstrated that this need can be partially addressed by in vivo examination of large mouse blood vessels, which are similar to human vessels used. Here, we present an alternative method for PAFC optimization that utilizes novel, clinically relevant phantoms resembling pigmented skin, tissue, vessels, and flowing blood. This phantom consists of a scattering-absorbing medium with a melanin layer and plastic tube with flowing beads to model light-absorbing red blood cells (RBCs) and circulating tumor cells (CTCs), as well as transparent beads to model white blood cells and clots. Using a laser diode, we demonstrated the extraordinary ability of PAFC to dynamically detect fast-moving mimic CTCs with positive PA contrast and white clots with negative PA contrast in an RBC background. Time-resolved detection of the delayed PA signals from blood vessels demonstrated complete suppression of the PA background from the modeled pigmented skin. This novel, medically relevant, dynamic blood flow phantom can be used to calibrate and maintain PAFC parameters for routine clinical applications.