A method to study cellular injuries using optical trapping combined with laser-induced shockwaves under quantitative phase microscope

There is a need for new methodologies to investigate cell apoptosis and recovery, cell adhesion, and cell-cell interactions in cellular biology and neurobiology. Such systems should be able to induce localized cell injuries and measure damage responses from single cells. In this regard, pulsed lasers can be used to produce Laser- Induced Shockwaves (LIS), which can cause cell detachments and induce cellular membrane injuries, by applying shear force in order of µN . Furthermore, since the resulting shear force can increase membrane permeability, chemicals and markers can then be transferred into cells non-invasively. Continuous-wave lasers can be used as Optical Tweezers (OT), to apply non-contact delicate forces, as low as 0.1f N , and deliver materials into cells, and also move the cells to different locations. In this paper, we introduce a combination of modalities to apply variable forces, from femto to micro newtons, to cells. Our system consists of a 1060nm continuous laser light source for OT and a 1030nm femtosecond pulsed laser for generating LIS. To have a direct measurement of changes in the cellular thickness and membrane dynamics, the cells are imaged under a Quantitative Phase Microscope (QPM). Our microscope is capable of Differential-Interference Microscopy (DIC) and Phase-Contrast microscopy (PhC) and fluorescent microscopy, making it a unique system for studying cell injuries.