Formation of blood clots, called thrombus, can happen due to hyper-coagulation of blood. Thrombi, while moving through blood vessels can impede blood flow, an important criterion for many critical diseases like deep vein thrombosis and heart attacks. Understanding mechanical properties of clot formation is vital for assessment of severity of thrombosis and proper treatment. However, biomechanics of thrombus is less known to clinicians and not very well investigated. Photoacoustic (PA) spectral response, a non-invasive technique, is proposed to investigate the mechanism of formation of blood clots through elasticity and also differentiate clots from blood. Distinct shift (increase in frequency) of the PA response dominant frequency during clot formation is reported. In addition, quantitative differentiation of blood clots from blood has been achieved through parameters like dominant frequency and spectral energy of PA spectral response. Nearly twofold increases in dominant frequency in blood clots compared to blood were found in the PA spectral response. Significant changes in energy also help in quantitatively differentiating clots from blood, in the blood. Our results reveal that increase in density during clot formation is reflected in the PA spectral response, a significant step towards understanding the mechanobiology of thrombus formation. Hence, the proposed tool, in addition to detecting thrombus formation, could reveal mechanical properties of the sample through quantitative photoacoustic spectral parameters.

The feasibility of continuous wave laser-based photoacoustic (CWPA) response technique in detecting the morphological changes in cells during the biological studies, through the features extracted from CWPA signal (i.e., amplitude) is demonstrated here. Various hematological disorders (e.g., sickle cell anemia, thalesemia) produce distinct changes at the cellular level morphologically. In order to explore the photoacoustic response technique to detect these morphological changes, we have applied CWPA technique onto the blood samples. Results of our preliminary study show a distinct change in the signal amplitude of photoacoustic (PA) signal due to a change in the concentration of blood, which signifies the sensitivity of the technique towards red blood cell (RBC) count (related to hematological disease like anemia). Further hypotonic and hypertonic solutions were induced in blood to produce morphological changes in RBCs (i.e., swollen and shrink, respectively) as compared to the normal RBCs. Experiments were performed using continuous wave laser-based photoacoustic response technique to verify the morphological changes in these RBCs. A distinct change in the PA signal amplitude was found for the distinct nature of RBCs (swollen, shrink, and normal). Thus, this can serve as a diagnostic signature for different biological studies based on morphological changes at cellular level. The experiments were also performed using conventional pulsed laser photoacoustic response technique which uses nano-second pulsed laser and the results obtained from both PA techniques were validated to produce identical changes. This demonstrates the utility of continuous wave laser-based photoacoustic technique for different biological studies related to morphological cellular disorders.

Breast cancer is the most prevalent form of cancer among women. Non-invasive and early stage diagnosis of breast cancer would be pragmatic to reduce unnecessary biopsy and mortality rate. We propose Wigner-Ville distribution (WVD) based photoacoustic spectral response (WVD-PASR), a tissue elasticity dependent technique for human breast cancer diagnosis. Since tissue elasticity acts as a finger print of many diseases including cancer, the proposed technique would differentiate normal from malignant breast masses. In addition, WVD is an advanced signal processing tool for timefrequency analysis which provides frequency domain parameters along with time information. This feature of WVD would elicit critical information about frequency component of the PA time domain signal. Since frequency content of PA signal is related to tissue elasticity, WVD-PASR would differentiate human breast masses. Applying the proposed technique on normal and malignant human breast tissues reveals that frequency analysis of malignant tissues contain two dominant peaks as compared to one dominant peak for a normal tissue. Besides having two dominant frequencies, the energy density of malignant breast is significantly more than that of normal tissue. Hence the proposed tool, in addition to detection of malignant breast tumours, could also provide tissue elasticity and other mechano-biological properties.

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We present the development of a laser diode based photoacoustic spectral response (PASR) setup capable of diagnosing human breast cancer tissues through the use of mechanobiological properties of the tissue. A detailed description of the laser driver is provided, highlighting the important characteristics of the developed driver. Furthermore, the amplifier development is described. The developed laser diode based PASR system has been characterized using standard samples. Subsequently, the developed experiment has been applied onto diagnosis of human breast tumors. Energy has been used as a parameter to differentiate between normal and malignant tissues. The results were statistically consistent and then compared with standard histopathology for correlation.