Classification of blood cells and tumor cells using label‐free ultrasound and photoacoustics

Abstract

A label-free method that can identify cells in a blood sample using high frequency photoacoustic and ultrasound signals is demonstrated. When the wavelength of the ultrasound or photoacoustic wave is similar to the size of a single cell (frequencies of 100-500 MHz), unique periodic features occur within the ultrasound and photoacoustic power spectrum that depend on the cell size, structure, and morphology. These spectral features can be used to identify different cell types present in blood, such as red blood cells (RBCs), white blood cells (WBCs), and circulating tumor cells. Circulating melanoma cells are ideal for photoacoustic detection due to their endogenous optical absorption properties. Using a 532 nm pulsed laser and a 375 MHz transducer, the ultrasound and photoacoustic signals from RBCs, WBCs, and melanoma cells were individually measured in an acoustic microscope to examine how the signals change between cell types. A photoacoustic and ultrasound signal was detected from RBCs and melanoma cells; only an ultrasound signal was detected from WBCs. The different cell types were distinctly separated using the ultrasound and photoacoustic signal amplitude and power spectral periodicity. The size of each cell was also estimated from the spectral periodicity. For the first time, sound waves generated using pulse-echo ultrasound and photoacoustics have been used to identify and size single cells, with applications toward counting and identifying cells, including circulating melanoma cells. V C 2015 International Society for Advancement of Cytometry

Biophysical isolation and identification of circulating tumor cells

“…Other unique alternatives to IF are emerging for CTC detection, including the use of surface plasmon resonance, 48 surface enhanced raman spectroscopy, 49 ultrasound and photoacoustics, 50 electrochemical aptasensors, 51 silicon nano-wire-array detection of magnetic upconversion nanoparticles, 52 light addressable potentiometric sensors, 53 impedance-based detection, 54 and PCR-based methods. 55,56 However, VDC remains a top candidate as a truly label-free enrichment and enumeration platform, supported with preliminary tests using clinical samples.…”

New advances in microfluidic flow cytometry

“…The frequencies used in the traditional photoacoustic systems are less than 100 MHz, which cannot detect the spectral features related to the size and sound speed of cell that occur within the 100–500 MHz frequency range . Most recently, to overcome the drawbacks of the PAFC, Kolios's group reported the simultaneous high frequency ultrasound and PAFC to count the cells in vitro .…”

Extended photoacoustic transport model for characterization of red blood cell morphology in microchannel flow

“…To illustrate, the RBCs of sickle cell disease have the most significant loss of deformability because of having different morphologies depending on its density [3][4][5][6]. The small changes in the morphology of RBCs are characterized by the absorption-based contrast of photoacoustic (PA) imaging which is complementary to other imaging modalities in terms of contrast mechanism, penetration, spatial resolution, and temporal resolution [7][8][9][10][11][12][13][14][15][16][17][18].…”