Opto-hydrodynamic fiber tweezers for stimulated Raman imaging cytometry of leukemic cells

Abstract

Raman fingerprinting of leukemic cells has potential applications in diagnosis and in vitro chemosensitivity assessment. A biochemical map of the contents of leukemic cells can not only help distinguish cancer patients from healthy ones but also shed light on different subtypes of leukemia such as ALL, AML, etc. Certain important requirements need to be fulfilled to effectively measure the Raman map of a single leukemic cell. Firstly, since the leukemia cells are suspension cells, it is preferred to keep them in a free solution rather than attached to a fixed surface during signal acquisition. Secondly, the cells need to be immobilized for several seconds, for the acquisition of the weak Raman signal even when using stimulated Raman Spectroscopy (SRS) which provides relatively stronger Raman signal. Thus, a device capable of sequentially flowing, holding, and releasing individual leukemia cells in a robust, efficient and high-throughput manner is required. We present an optofluidic fiber tweezers device comprised of a novel combination of 3D hydrodynamic flow focusing and optical fiber in a microfluidic chip. By exploiting the interplay between the optical and hydrodynamic forces acting on the cell, we demonstrate rapid, efficient, sequential delivery and trapping of single leukemic cells in a flow cytometer format followed by SRS imaging of the trapped cell. The specific Raman vibration bands corresponding to the lipids, nucleic acids, and proteins in the trapped cells were analyzed to distinguish cancerous cells from healthy cells. Our device is also capable of isolating cells with unique Raman signatures for further processing using techniques like gene sequencing etc.