THE DECADE OF THE RABiT (2005-15).

The RABiT (Rapid Automated Biodosimetry Tool) is a dedicated Robotic platform for the automation of cytogenetics-based biodosimetry assays. The RABiT was developed to fulfill the critical requirement for triage following a mass radiological or nuclear event. Starting from well-characterized and accepted assays we developed a custom robotic platform to automate them. We present here a brief historical overview of the RABiT program at Columbia University from its inception in 2005 until the RABiT was dismantled at the end of 2015. The main focus of this paper is to demonstrate how the biological assays drove development of the custom robotic systems and in turn new advances in commercial robotic platforms inspired small modifications in the assays to allow replacing customized robotics with 'off the shelf' systems. Currently, a second-generation, RABiT II, system at Columbia University, consisting of a PerkinElmer cell::explorer, was programmed to perform the RABiT assays and is undergoing testing and optimization studies.

[1]  Mikhail Repin,et al.  Development of a High-Throughput and Miniaturized Cytokinesis-Block Micronucleus Assay for Use as a Biological Dosimetry Population Triage Tool , 2015, Radiation research.

[2]  D. Bojanic,et al.  Impact of high-throughput screening in biomedical research , 2011, Nature Reviews Drug Discovery.

[3]  Sam Michael,et al.  A robotic platform for quantitative high-throughput screening. , 2008, Assay and drug development technologies.

[4]  Jian Zhang,et al.  DESIGN AND PRELIMINARY VALIDATION OF A RAPID AUTOMATED BIODOSIMETRY TOOL FOR HIGH THROUGPUT RADIOLOGICAL TRIAGE. , 2009, Proceedings of the ... ASME Design Engineering Technical Conferences. ASME Design Engineering Technical Conferences.

[5]  H Thierens,et al.  Cytogenetic biodosimetry of an accidental exposure of a radiological worker using multiple assays. , 2005, Radiation protection dosimetry.

[6]  Jian Zhang,et al.  THE RABIT: A RAPID AUTOMATED BIODOSIMETRY TOOL FOR RADIOLOGICAL TRIAGE , 2010, Health physics.

[7]  Michael Lichten,et al.  Techniques for γ‐H2AX Detection , 2006 .

[8]  D. Brenner,et al.  γ-H2AX Kinetic Profile in Mouse Lymphocytes Exposed to the Internal Emitters Cesium-137 and Strontium-90 , 2015, PloS one.

[9]  Leonora Marro,et al.  Biological Dosimetry by the Triage Dicentric Chromosome Assay - Further validation of International Networking. , 2011, Radiation measurements.

[10]  Mikhail Repin,et al.  Next generation platforms for high-throughput biodosimetry. , 2014, Radiation protection dosimetry.

[11]  Jian Zhang,et al.  Design Considerations for a Minimally Invasive High-Throughput Automation System for Radiation Biodosimetry , 2007, 2007 IEEE International Conference on Automation Science and Engineering.

[12]  T. Lörch,et al.  New developments in automated cytogenetic imaging: unattended scoring of dicentric chromosomes, micronuclei, single cell gel electrophoresis, and fluorescence signals , 2004, Cytogenetic and Genome Research.

[13]  Wang Li,et al.  A 5.5Mpixel 100 frames/sec wide dynamic range low noise CMOS image sensor for scientific applications , 2010, Electronic Imaging.

[14]  M. Prakash Hande,et al.  Stable Intrachromosomal Biomarkers of Past Exposure to Densely Ionizing Radiation in Several Chromosomes of Exposed Individuals , 2004, Radiation research.

[15]  Jason C. Tsui,et al.  Liquid Handling Optimization in High-Throughput Biodosimetry Tool. , 2016, Journal of medical devices.

[16]  Y. Yao,et al.  Adapting the γ-H2AX Assay for Automated Processing in Human Lymphocytes. 1. Technological Aspects , 2011, Radiation research.

[17]  Jian Zhang,et al.  Automated recognition of robotic manipulation failures in high-throughput biodosimetry tool , 2012, Expert Syst. Appl..

[18]  Y. Lawrence Yao,et al.  Development of a robotically-based automated biodosimetry tool for high-throughput radiological triage , 2010 .

[19]  I. Hayata,et al.  Robot system for preparing lymphocyte chromosome. , 1992, Journal of Radiation Research.

[20]  Andrew Karam,et al.  Infrastructure to support ultra high throughput biodosimetry screening after a radiological event , 2011, International journal of radiation biology.

[21]  Mark H Lowenberg,et al.  Proceedings of the ASME Design Engineering Technical Conference , 2009 .

[22]  D. Brenner,et al.  The RABiT: high-throughput technology for assessing global DSB repair , 2014, Radiation and environmental biophysics.

[23]  D. Brenner,et al.  Fast Image Analysis for the Micronucleus Assay in a Fully Automated High-Throughput Biodosimetry System , 2014, Radiation research.

[24]  Hongliang Wang,et al.  The RABiT: A Rapid Automated Biodosimetry Tool for radiological triage. II. Technological developments , 2011, International journal of radiation biology.

[25]  M. Fenech,et al.  HUMN project: detailed description of the scoring criteria for the cytokinesis-block micronucleus assay using isolated human lymphocyte cultures. , 2003, Mutation research.

[26]  D. Brenner,et al.  In vitro RABiT measurement of dose rate effects on radiation induction of micronuclei in human peripheral blood lymphocytes , 2016, Radiation and environmental biophysics.

[27]  W. Janzen,et al.  Screening technologies for small molecule discovery: the state of the art. , 2014, Chemistry & biology.

[28]  Sara Rockwell,et al.  Priority List of Research Areas for Radiological Nuclear Threat Countermeasures , 2005, Radiation research.

[29]  Mikhail Repin,et al.  Platform-Dependent Liquid Handling in High-Throughput Biodosimetry Tool , 2016 .

[30]  A. Jauch,et al.  mBAND: a high resolution multicolor banding technique for the detection of complex intrachromosomal aberrations , 2004, Cytogenetic and Genome Research.

[31]  D. Brenner,et al.  High Throughput Measurement of γH2AX DSB Repair Kinetics in a Healthy Human Population , 2015, PloS one.

[32]  Markus Voelter,et al.  State of the Art , 1997, Pediatric Research.

[33]  A. Dove High-throughput screening goes to school , 2007, Nature Methods.

[34]  Mikhail Repin,et al.  An automated imaging system for radiation biodosimetry , 2015, Microscopy research and technique.

[35]  Michael Lichten,et al.  Techniques for gamma-H2AX detection. , 2006, Methods in enzymology.

[36]  P. Prasanna,et al.  Sample Tracking in an Automated Cytogenetic Biodosimetry Laboratory for Radiation Mass Casualties. , 2007, Radiation measurements.

[37]  D. Brenner,et al.  Accelerator-Based Biological Irradiation Facility Simulating Neutron Exposure from an Improvised Nuclear Device , 2015, Radiation research.