The Ikoniscope platform was initially developed for rare-cell detection, with a view to applying it to the detection and analysis of fetal cells in the circulation of pregnant women, for non-invasive prenatal diagnosis. Validation of the efficacy of this technology was provided by a series of articles (1-3) reporting the high degree of sensitivity and specificity of the platform. In one example example, the Ikoniscope was able to detect between 1 and 10 rare fetal cells in a background of 2 to 5 million maternal cells (2).
Following this initial success, a number of diagnostic FISH tests were developed to run on the Ikonisys platform. The platform itself was cleared by the FDA for automated fluorescence in situ hybridization (FISH) testing, as were three specific diagnostic tests: fastFISH amnio, oncoFISH bladder and oncoFISH her2. The fastFISH amnio automated FISH test for prenatal diagnosis of the 5 most common chromosomal disorders was validated as a highly desirable approach to routine prenatal diagnosis (4). oncoFISH bladder, an automated FISH test developed for diagnosis and monitoring recurrence of urothelial cancer, was shown (5) to afford the benefit of high-throughput while providing the user with the necessary images and tools to quickly and accurately report a case. Of particular note, was the fact that greater than 96% of samples could be reported directly with no requirement for manual review, the best of available automated microscopy systems. The oncoFISH her2 test was developed for determination of the HER2 amplification status of breast tumor specimens, critical for determining appropriate treatment of patients with breast cancer. Validation of the Ikoniscope-oncoFISH her2 test (6) noted the consistency offered by the automated system as well as the benefit of recording all images produced for a case in allowing multiple reviewers of a difficult or equivocal case and providing a permanent case record.
In addition to the 3 FDA cleared tests, a number of applications were developed to utilize the Ikoniscope for laboratory developed diagnostic tests. Of particular note is the oncoFISH cervical application that allows liquid cytology specimens to be analysed for the presence of rare cells with amplification of the chromosome 3q locus. Several publications (8-10) demonstrated the unique ability of the Ikoniscope to distinguish low grade cervicalcancer lesions unlikely to progress that could be managed conservatively, from those likely to progress to a high grade lesion that require more immediate treatment. Similarly, the use of the Ikoniscope has been validated for lung (11) and oral (12) cancer testing.
In summary, the Ikoniscope platform, initially developed for rare-cell analysis in prenatal diagnosis, has been extensively validated in a number of published studies that demonstrate its value in prenatal and cancer testing. Moving forward, there is scope to continue to expand the number of applications of the Ikoniscope platform, particularly with respect to companion diagnostics.
1) Automated detection of rare fetal cells in maternal blood: Eliminating the false-positive XY signals in XX pregnancies. Kilpatrick et al, AmJObstetGynecol 2004.
2) Detection of circulating fetal cells utilizing automated microscopy: potential for noninvasive prenatal diagnosis of chromosomal aneuploidies. Seppo et al, PrenatalDiagn 2008.
3) Prenatal diagnosis of trisomy 21 through detection of trophoblasts in cervical smears. Sifakis et al, 2010
4) Fully automated FISH examination of amniotic fluid cells. Wauters et al, PrenatalDiagn 2007
5) Digitized Microscopy in the Diagnosis of Bladder Cancer. Marganski et al, CancerCytopathol 2011
6) Determination of HER2 Gene Status by Fully Automated Fluorescence Microscopy. Ross et al, AQCH 2011
7) Her-2/neu Status Detection in Fluorescence In-Situ Hybridization (FISH) Image Stack. Yu et al, ICPR 2008
8) Amplification of the 3q chromosomal region as a specific marker in cervical cancer. Wright TC et al, Am J Obstet Gynecol. 2015
9) 3q26 Amplification Is an Effective Negative Triage Testfor LSIL: A Historical Prospective Study. Harper DM, PLoSONE 2012
10) Role of Chromosome 3q26 Gain in PredictingProgression of Cervical Dysplasia. Rodolakis et al, IJGC 2012.
11) Gain of hTERC: a genetic marker of malignancy in oral potentially malignant lesions. Dorji et al, HumanPathol 2015.
12) Automation of ALK gene rearrangement testing with fluorescence in situ hybridization (FISH): a feasibility study. Zwaenepoel et al, ExpMolPathol 2015