Development of microfluidic acoustic flow cytometry based on simultaneous ultrasound backscatter and photoacoustics for micron and sub-micron size objects

I developed a flow cytometer based on simultaneous detection of ultra-high frequency ultrasound backscatter and photoacoustic waves from individual micron scale objects, such as, cells, microparticles, and microbubbles owing in a microuidic channel. Individual micron scale objects are ow focused through a focal zone, where both ultrasound and laser pulses focus, in a microchannel of a polydimethylsiloxane (PDMS) based microuidic device. At the focal zone, the objects are simultaneously insonified by ultrasound (center frequency 375 MHz) and irradiated by nanosecond laser (532 nm wavelength) pulses. The interactions generate ultrasound backscatter and photoacoustic signals from the individual objects, which are strongly dependent on their size, morphology, and biomechanical properties, such as the Young's modulus, and optical absorption properties. These parameters can be extracted by analyzing the unique spectral features of the detected signals. At frequencies less than 100 MHz, the signals from the micron scale objects do not contain these unique spectral signatures, thus higher frequencies are required. Cell analysis is the main application of interest using the acoustic flow cytometer. Combining ultrasound backscatter and photoacoustics results in sufficient information about a single cell that can be used for single cell analysis and for diagnostics applications. However, the usage of this system is not limited to biological cells. This system can also be used for analyzing individual microbubbles, which are used as ultrasound contrast agents. During my research, a novel microuidic technique is developed to generate microbubbles of desired sizes by shrinking microbubbles from O(100) _m by applying a suitable vacuum pressure. These shrunken bubbles of different sizes can be used as samples to validate the acoustic ow system for microbubble analysis.

Development of microfluidic acoustic flow cytometry based on simultaneous ultrasound backscatter and photoacoustics for micron and sub-micron size objects

I developed a flow cytometer based on simultaneous detection of ultra-high frequency ultrasound backscatter and photoacoustic waves from individual micron scale objects, such as, cells, microparticles, and microbubbles owing in a microuidic channel. Individual micron scale objects are ow focused through a focal zone, where both ultrasound and laser pulses focus, in a microchannel of a polydimethylsiloxane (PDMS) based microuidic device. At the focal zone, the objects are simultaneously insonified by ultrasound (center frequency 375 MHz) and irradiated by nanosecond laser (532 nm wavelength) pulses. The interactions generate ultrasound backscatter and photoacoustic signals from the individual objects, which are strongly dependent on their size, morphology, and biomechanical properties, such as the Young's modulus, and optical absorption properties. These parameters can be extracted by analyzing the unique spectral features of the detected signals. At frequencies less than 100 MHz, the signals from the micron scale objects do not contain these unique spectral signatures, thus higher frequencies are required. Cell analysis is the main application of interest using the acoustic flow cytometer. Combining ultrasound backscatter and photoacoustics results in sufficient information about a single cell that can be used for single cell analysis and for diagnostics applications. However, the usage of this system is not limited to biological cells. This system can also be used for analyzing individual microbubbles, which are used as ultrasound contrast agents. During my research, a novel microuidic technique is developed to generate microbubbles of desired sizes by shrinking microbubbles from O(100) _m by applying a suitable vacuum pressure. These shrunken bubbles of different sizes can be used as samples to validate the acoustic ow system for microbubble analysis.