Nacancell

The project aims to develop a new diagnostic test platform that will facilitate the diagnosis of diseases in which a) the current diagnostic methods are costly, time consuming and a burden for the patients and/or b) it is difficult to prove a given disease with current technology. The main focus of the project will be to develop a test and associated diagnostic instrumentation using a simple blood test for diagnosing Neuroblastoma, a malignant type of tumor, in children. If disease is detected, the same diagnostic test platform could be used to follow the development of tumor and response to medication. The latter is an equally important factor for motivation to develop this new test platform. Methods that can provide accurate and quick answers without great burden for the patient to an economic price are a key factor in driving the project. Although the main focus of the project will be to a given type of cancer, the diagnostic platform is relatively easily adaptable to other types of cancer and other disease groups. Partner A has its core competencies related to the development of diagnostic tests. They want the project to focus on the development of a "quick test", using nanoparticles to increase the sensitivity versus traditional "rapid tests" Partner B has its core competencies related to the design of biochemical molecules that can be "tailored" to detect unique biomolecules present in a blood sample. Partner A will use the biochemical molecules developed by Partner B in the development of "rapid test" Partner C has specific knowledge about the diagnosis and treatment of patients with Neuroblastoma. Partner D (Skannex) has its core competencies related to the development of software and instrumentation for accurate and easily reading/reporting of rapid tests including lateral flow assays. During first part of the project period Partner A developed a first variant of the "tags" used in the first prototype of the lateral flow assay (LFA). Partner B developed and small-scale synthesized the first aptamer to be tested in the prototype LFA. Partner C has given input to Partner B for the aptamer design versus PTHLH, the protein that shall be detected. Partner D has developed software that can read colorimetric signals from the test format Patner A is using in the prototype development of the LFA using two different image capturing methods; scanner and camera. The goal has been to develop aptamer for N-terminal of the peptide, but this has been complicated. Aptamer for mid-region has therefore been used for further development of the assay to be able to move forward. In the meantime a lot of time has been used on development of aptamer for the N-terminal. To do so the SELEX method has been used. SPR (surface plasmon resonance) analysis has been used for confirming that the selected aptamer selectively is binding to PTHLH. Partner C has evaluated PTHLH in clinical samples from different cell lines for diagnostic purpose. Partner D and A have been discussing development of a fluorescence reader. Partner D has developed an instrument for reading both colorimetric and fluorescence assays. Partner A has received this. Partner A has developed a Lateral-Electrophoretic bioassay to obtain more distinct control and test lines. They have also developed a fluorescence assay for the same analyte. Partner A has synthesized three different nanoparticles to be used in different types of lateral flow assays (LFA): Gold particles in regular colorimetric LFA, oxide nanoparticles in electrophoretic LFA and QD (Quantum Dots) for the detection in fluorescent LFA. All three types of assays have been developed with the use of these nanoparticles and antibodies to be able to detect PTHLH and H-IgG as a proof of concept. Partner D has further developed the combined reader by suing a better smartphone and optimized software. Due to the problems during development of aptamer for the N-terminal partner A decided to order a production of antibodies against the N-terminal. In the meantime partner A continued the work with Lateral-Electrophoretic bioassay as a strategy for detection of PTHLH in complex samples such as serum and whole blood. The results were very promising and was submitted to European patent for protection of the technology. Competitive LFA was performed to find the optimal assay conditions and this work is ongoing to obtain conditions equal to clinical values. Partner A has started the development of LFA against the N-terminal with use of the ordered antibodies. The Lateral flow reader developed by partner D has been used in this work. Partner C has been trained in the use for this reader to be able to use it in the evaluation of the clinical samples as soon as the assay has been developed.

Utviklingen av lateral flow assay for deteksjon av PTHLH vil være av stor betydning i kliniske undersøkelser. Både som et diagnostik verktøy, men også til bruk i monitorering og oppfølging av pasienter. Selv om det i første omgang vil bli brukt på en bestemt type kreft (neuroblastoma), vil samme teknologi kunne brukes på andre kreftformer. Ved å bruke SkanMulti og/eller SkanEasy som instrument for avlesing av assays, vil man få objektive og presise resultater på en brukervennlig måte som gir gode rapporter og arkivering av data. Instrumentene lar seg enkelt tilpasse til avlesing av andre lateral flow assays og kan derfor også brukes for andre typer kreftfomer.Skannex har som resultat av dette prosjeket utviklet en fungerende prototype på en fluorescens leser.

NACANCELL aims at developing an innovative paper-based sensor to quantify parathyroid hormone-like hormone (PTHLH), a protein that exerts critical roles in cancer. The project will focus on neuroblastoma, a childhood cancer, but will impact the field of clinical oncology and cancer research as well through its future easy application to other biomarkers. The main objective will be to generate an innovative device to monitor PTHLH production in in vitro cancer models as well as in plasma samples of cancer patients. This will allow for a fast, easy and cost effective monitoring of cancer cells activity for research purposes, but, more importantly, it will provide a precise evaluation of tumor evolution and response to treatments in liquid biopsies of cancer patients. Although the project will focus on a particular developmental tumour, the same scenario applies for the vast majority of cancers presented in paediatric and adult patients.