Lightsheet-based flow cytometer for whole blood with the ability for the magnetic retrieval of objects from the blood flow

Detection and extraction of circulating tumor cells and other rare objects in the bloodstream are of great interest for modern diagnostics, but devices that can solve this problem for the whole blood volume of laboratory animals are still rare. Here we have developed SPIM-based lightsheet flow cytometer for the detection of fluorescently-labeled objects in whole blood. The bypass channel between two blood vessels connected with the external flow cell was used to visualize, detect, and magnetically separate fluorescently-labeled objects without hydrodynamic focusing. Carriers for targeted drug delivery were used as model objects to test the device performance. They were injected into the bloodstream of the rat, detected fluorescently, and then captured from the bloodstream by a magnetic separator prior to filtration in organs. Carriers extracted from the whole blood were studied by a number of in vitro methods

The Influence of Magnetic Composite Capsule Structure and Size on Their Trapping Efficiency in the Flow

A promising approach to targeted drug delivery is the remote control of magnetically sensitive objects using an external magnetic field source. This method can assist in the accumulation of magnetic carriers in the affected area for local drug delivery, thus providing magnetic nanoparticles for MRI contrast and magnetic hyperthermia, as well as the magnetic separation of objects of interest from the bloodstream and liquid biopsy samples. The possibility of magnetic objects’ capture in the flow is determined by the ratio of the magnetic field strength and the force of viscous resistance. Thus, the capturing ability is limited by the objects’ magnetic properties, size, and flow rate. Despite the importance of a thorough investigation of this process to prove the concept of magnetically controlled drug delivery, it has not been sufficiently investigated. Here, we studied the efficiency of polyelectrolyte capsules’ capture by the external magnetic field source depending on their size, the magnetic nanoparticle payload, and the suspension’s flow rate. Additionally, we estimated the possibility of magnetically trapping cells containing magnetic capsules in flow and evaluated cells’ membrane integrity after that. These results are required to prove the possibility of the magnetically controlled delivery of the encapsulated medicine to the affected area with its subsequent retention, as well as the capability to capture magnetically labeled cells in flow

Detection of Rare Objects by Flow Cytometry: Imaging, Cell Sorting, and Deep Learning Approaches

Flow cytometry nowadays is among the main working instruments in modern biology paving the way for clinics to provide early, quick, and reliable diagnostics of many blood-related diseases. The major problem for clinical applications is the detection of rare pathogenic objects in patient blood. These objects can be circulating tumor cells, very rare during the early stages of cancer development, various microorganisms and parasites in the blood during acute blood infections. All of these rare diagnostic objects can be detected and identified very rapidly to save a patient’s life. This review outlines the main techniques of visualization of rare objects in the blood flow, methods for extraction of such objects from the blood flow for further investigations and new approaches to identify the objects automatically with the modern deep learning methods