The main objective of the study is to develop a microfluidics-based system for the in vitro monitoring of blood inflammation and coagulation. More specifically the project aims to:
- Advance the current knowledge in microfluidic blood flow, microscale blood rheology, and digital bio-image processing, through the application of Bio -Rheology, -Fluid Mechanics, -Microfluidics and Digital Signal Processing methods and techniques.
- Develop a disease monitoring system, which is of low cost, easily transported and operated, and e-health compatible for the simultaneous assessment of inflammation and coagulation, which will provide therapy monitoring at the point of care or in the home.
- Validate the performance of the system through a pilot clinical study. Clinical studies will be performed in the Department of Rheumatology at the Nicosia General Hospital. Rheumatology experts from the Rheumatology Department of Kings College Hospital-UK will be involved in this task.
Milestones of the Project
MILESTONE 1. Development of algorithms for the detection of Inflammation and Coagulation in blood. The objective of this task is to develop sensitive indices for the detection of changes in the micro-structure of blood caused by inflammation/coagulation.
Milestone 1 regards the establishment of the indices for inflammation and coagulation. This task is described in the Deliverable D3-1-ESR-RBCA-CT-ALGORITHMS. In brief, algorithms have been developed for the derivation of indices using image processing techniques on blood samples, and three reports have been produced for journal publications. One report is published in Physics of Fluids, one report is prepared for submission in Biosensors and one report is under preparation for submission in Scientific Reports (or Physics of Fluids). In these reports image processing algorithms and techniques for the assessment of red blood cell aggregation, whole blood coagulation and RBC velocity (for the ESR index) are presented. These Publications are the following:
- Pasias D., Passos A., G. Constantinides, Balabani S. and Kaliviotis E. (2020). Surface tension driven flow of blood in a rectangular microfluidic channel: effect of erythrocyte aggregation. Physics of Fluids, 32, 071903, doi.org/10.1063/5.0008939.
- Louka M. and Kaliviotis E. Development of an optical method for whole blood coagulation evaluation in a drop of blood. Biosensors. Submitted January 2021 – Currently under revision.
- Pasias D., Passos A., G. Constantinides, L. Koytsokeras, Balabani S. and Kaliviotis E. (2021). Effects of erythrocyte aggregation, haematocrit and deformability in the flow characteristics of blood, flowing in a TiO2 coated microfluidic channel. In preparation for submission.
MILESTONE 2. Design of the device hardware and in vitro evaluation: The functional hardware of the system. The aim in this task is to develop the hardware of the system. Specifically, Milestone 2 regards the completion of the microfluidic cartridge, the construction of the first stage of the hardware, and test initiation. A report has been completed and delivered to project partners. Bellow are described the main achievements.
Microfluidic cartridge. The first functional microfluidics cartridge (part of WP4) is described in the manuscript prepared for publication by Pasias etal:
- Pasias D., Passos A., G. Constantinides, L. Koytsokeras, Balabani S. and Kaliviotis E. (2020). Effects of erythrocyte aggregation, haematocrit and deformability in the flow characteristics of blood, flowing in a TiO2 coated microfluidic channel. In preparation for submission.
The chip consists of glass plates, enclosing a double-sided adhesive tape forming the fluidic channel in which the sample is placed. The glasses are treated with an appropriate protocol, which enhance the flow intensity. The channel is of a converging geometry, which also has a positive effect in the flow.
First stage of hardware. The first functional hardware set-up (part of WP4), has been tested for various aspects of its performance. It consists of a camera unit, a microprocessor and peripherals. The hardware collects data from the microfluidic chip, processes the results in the microprocessor and produces the results (measuring indices). The hardware was subsequently integrated in various versions of the first pre-industrial prototype. Figure 3 illustrates the independent functional device.
Test initiation. In vitro tests (part of the WP5) have been performed on treated and finger-prick blood samples. Results have been obtained from a series of tests. Preliminary results of blood inflammation and coagulation are promising. The time dependent behaviour of the relevant data are further analyzed to produce relevant indices. The methodology and the developed indices are explained in detail in the manuscript under revision:
- Marinos Louka and Efstathios Kaliviotis. Development of an optical method for whole blood coagulation evaluation in a drop of blood. Biosensors. Submitted January 2021 – Under revision.
Further tests were performed to assess the erythrocyte sedimentation rate of the tested samples. For the particular test the sedimentation of the cells is observed directly. Results were compared with a commercial instrument and show good agreement.
MILESTONE 3. Design of the software: The controlling application. The work involves managing of the captured data, the data processing in the appropriate operating systems (Android / IOS), the user interface, and the communication of the data.
MILESTONE 4. Clinical evaluation of the prototype hardware device: Clinical performance of the device. The aim in this task is the examination of the correlation between the inflammation/coagulation indices produced by the system, with those obtained by the conventional inflammatory markers n the clinical laboratory.
