Micro-ultrasonic Assessment of Early Stage Clot Formation and Whole Blood Coagulation Using an All-Optical Ultrasound Transducer and Adaptive Signal Processing Algorithm.

Abnormal formation of solid thrombus inside a blood vessel can cause thrombotic morbidity and mortality. This necessitates early stage diagnosis, which requires quantitative assessment with a small volume, for effective therapy with low risk to unwanted development of various diseases. We propose a micro-ultrasonic diagnosis using an all-optical ultrasound-based spectral sensing (AOUSS) technique for sensitive and quantitative characterization of early stage and whole blood coagulation. The AOUSS technique detects and analyzes minute viscoelastic variations of blood at a micro-ultrasonic spot (<100 µm) defined by laser-generated focused ultrasound (LGFU). This utilizes (1) a uniquely designed optical transducer configuration for frequency-spectral matching and wideband operation (6 dB widths: 7-32 MHz and d.c. ∼ 46 MHz, respectively) and (2) an empirical mode decomposition (EMD)-based signal process particularly adapted to nonstationary LGFU signals backscattered from the spot. An EMD-derived spectral analysis enables one to assess viscoelastic variations during the initiation of fibrin formation, which occurs at a very early stage of blood coagulation (1 min) with high sensitivity (frequency transition per storage modulus increment = 8.81 MHz/MPa). Our results exhibit strong agreement with those obtained by conventional rheometry (Pearson's R > 0.95), which are also confirmed by optical microscopy. The micro-ultrasonic and high-sensitivity detection of AOUSS poses a potential clinical significance, serving as a screening modality to diagnose early stage clot formation (e.g., as an indicator for hypercoagulation of blood) and stages of blood-to-clot transition to check a potential risk for development into thrombotic diseases.

Stretchable and Robust Candle-Soot Nanoparticle-Polydimethylsiloxane Composite Films for Laser-Ultrasound Transmitters.

Considerable attention has been devoted to the development of nanomaterial-based photoacoustic transmitters for ultrasound therapy and diagnosis applications. Here, we fabricate and characterize candle-soot nanoparticles (CSNPs) and polydimethylsiloxane (PDMS) composite-based photoacoustic transmitters, based on a solution process, not just to achieve high-frequency and high-amplitude pressure outputs, but also to develop physically stretchable ultrasound transmitters. Owing to its non-porous and non-agglomerative characteristics, the composite exhibits unique photo-thermal and mechanical properties. The output pressure amplitudes from CSNPs-PDMS composites were 20-26 dB stronger than those of Cr film, used as a reference. The proposed transmitters also offered a center frequency of 2.44-13.34 MHz and 6-dB bandwidths of 5.80-13.62 MHz. Importantly, we characterize the mechanical robustness of CSNPs-PDMS quantitatively, by measuring laser-damage thresholds, to evaluate the upper limit of laser energy that can be ultimately used as an input, i.e., proportional to the maximum-available pressure output. The transmitters could endure an input laser fluence of 54.3-108.6 mJ·cm-2. This is 1.65-3.30 times higher than the Cr film, and is significantly higher than the values of other CSNPs-PDMS transmitters reported elsewhere (22-81 mJ·cm-2). Moreover, we characterized the strain-dependent photoacoustic output of a stretchable nanocomposite film, obtained by delaminating it from the glass substrate. The transmitter could be elongated elastically up to a longitudinal strain of 0.59. Under this condition, it maintained a center frequency of 6.72-9.44 MHz, and 6-dB bandwidth ranges from 12.05 to 14.02 MHz. We believe that the stretchable CSNPs-PDMS composites would be useful in developing patch-type ultrasound devices conformally adhered on skin for diagnostic and therapeutic applications.