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Development of a new high throughput automated imaging system to carry out drug sensitivity measurements on primary leukemia/lymphoma cells to assist individualized assay guided therapy

Final Report Summary - AISAT (Development of a new high throughput automated imaging system to carry out drug sensitivity measurements on primary leukemia/lymphoma cells to assist ... therapy)

The aim of the project was to build a new robust prototype of a high throughput automated imaging system that can be used in routine clinical lab environment for gathering data on drug sensitivity patterns of primary leukaemia/lymphoma cells. The new device will assist individualised assay guided therapy of cancer patients. Dr Savchenko, a very talented young solid-state physicist from Kiev, Ukraine was recruited to design, build, program and test the early prototypes of the device. Dr Savchenko solved the task successfully.

The major technical/conceptual challenge of the project was to provide a robust and affordable alternative to the currently existing high throughput microscopic imaging devices that represent the state of art technology in pharmaceutical industry for microscopy based cellular drug screening assays. The current devices are very expensive, bulky and slow and as such are not suitable for routine clinical diagnostic or academic research use.

Dr Savchenko solved the problem by completely redesigning the optical visualisation pathway of the microscope, replacing the standard epifluorescence illumination path with light emitting diode based, capillary fibre guided multiangle oblique illumination; parallelising the capture procedure to accommodate six parallel imaging units; redesigning all movable part for full automatic three dimensional control of the samples and movements of emission filter sets; by replacing bulky cameras with high sensitivity, high resolution CMOS chips; designing and creating integrated electronic circuit boards for primary image capture, illumination control, high precision movement motor control and data integration; writing a series of computer software that allow single push bottom operation with automatic auto-focusing, multicolor image collection and adaptive image correction.

The device that we call Hexascope 3.0 underwent a series of successive improvement and redesign cycles until it reached its current form. The fully functioning prototype is a small bench-top size device that can image the entire area of a standard 384 well cell culture plate in 3 different colours at a resolution that allows not only the evaluation of all cancer cells that were seeded on the plate but even to provide detailed morphometric parameters for so called HCA (high content analysis) imaging.

We have successfully employed two Hexascope 3.0 devices in our newly developed in vitro viability (iVV) assay where we can determine the anti-cancer drug sensitivity of human cancer cells that were isolated from the patient's blood or body cavity fluids. With the help of the Hexascope now we can routinely measure the effect of thirty different drugs at four different concentrations, in triplicates, on a single robot-printed 384 well plate. Currently we test the devices by analysing primary leukemic blood samples that we receive from several onco-hematological clinics from Hungary and Sweden. The devices already clinically useful information to oncologists to assist the individualised, assay based therapy of cancer patients.

We also aimed to provide this new technology to clinical laboratories and academic institutions to facilitate both direct patient care and also high through put assay based drug discovery in academic settings. Our technology will also provide the infrastructural backbone of the anticancer drug discovery activity of the ACT! (Advanced Cancer Therapies) strategic research centre at the Karolinska Institutet.