In vivo flow cytometry: a horizon of opportunities

Abstract

Flow cytometry (FCM) has been a fundamental tool of biological discovery for many years. Invasive extraction of cells from a living organism, however, may lead to changes in cell properties and prevents studying cells in their native environment. These problems can be overcome by use of in vivo FCM, which provides detection and imaging of circulating normal and abnormal cells directly in blood or lymph flow. The goal of this review is to provide a brief history, features, and challenges of this new generation of FCM methods and instruments. Spectrum of possibilities of in vivo FCM in biological science (e.g., cell metabolism, immune function, or apoptosis) and medical fields (e.g., cancer, infection, and cardiovascular disorder) including integrated photoacoustic-photothermal theranostics of circulating abnormal cells are discussed with focus on recent advances of this new platform.

Fig. 1

Principle of in vivo flow cytometry integrating multimodal detection of individual circulating cells directly in the bloodstream or lymph flow.

Fig. 2

High-speed transmittance digital microscopy (TDM) images of cells in the space within the valve area (left) and immediate after a valve (right) of the lymph vessel of rat mesentery at ×10 (top) and ×100 (bottom) magnifications demonstrating the principle of cell flow hydrodynamic focusing. TDM images of cells in the central part of a lymphangion in diastole (top, right) and systole (bottom, right) phases are also shown [from (26)].

Fig.3

In vivo magnetic enrichment and multiplex two – color photoacoustic (PA) detection of circulating tumor cells (CTCs) molecularly targeted by cocktail of golden carbon nanotubes (GNTs) and magnetic nanoparticles (MNP) [from (15)].

Fig.4

(a) Schematic of in vivo PA flow cytometry (FCM). (b) Clinical prototype of personal in vivo PA FCM (from [29,41]).