Sample tracking in an automated cytogenetic biodosimetry laboratory for radiation mass casualties

Abstract

Chromosome aberration-based dicentric assay is expected to be used after mass casualty lifethreatening radiation exposures to assess radiation dose to individuals. This will require processing of a large number of samples for individual dose assessment and clinical triage to aid treatment decisions. We have established an automated, high-throughput, cytogenetic biodosimetry laboratory to process a large number of samples for conducting the dicentric assay using peripheral blood from exposed individuals according to internationally accepted laboratory protocols (i.e., within days following radiation exposures). The components of an automated cytogenetic biodosimetry laboratory include blood collection kits for sample shipment, a cell viability analyzer, a robotic liquid handler, an automated metaphase harvester, a metaphase spreader, high-throughput slide stainer and coverslipper, a high-throughput metaphase finder, multiple satellite chromosome-aberration analysis systems, and a computerized sample tracking system. Laboratory automation using commercially available, off-the-shelf technologies, customized technology integration, and implementation of a laboratory information management system (LIMS) for cytogenetic analysis will significantly increase throughput. This paper focuses on our efforts to eliminate data transcription errors, increase efficiency, and maintain samples' positive chain-of-custody by sample tracking during sample processing and data analysis. This sample tracking system represents a "beta" version, which can be modeled elsewhere in a cytogenetic biodosimetry laboratory, and includes a customized LIMS with a central server, personal computer workstations, barcode printers, fixed station and wireless hand-held devices to scan barcodes at various critical steps, and data transmission over a private intra-laboratory computer network. Our studies will improve diagnostic biodosimetry response, aid confirmation of clinical triage, and medical management of radiation exposed individuals.

High-throughput sample processing and sample management; the functional evolution of classical cytogenetic assay towards automation.

“…A laboratory information management system (LIMS) is central to the automation of the workflow in a cytogenetic biodosimetry laboratory, which involves automation of various modules: sample acquisition, sample processing, image acquisition, chromosome aberration analyses, dose estimation and reporting. Our initial efforts on development and implementation of a LIMS to eliminate data transcription errors, increase efficiency, and maintain positive chain-of-custody of samples by sample tracking during sample processing and chromosome-aberration analysis has been previously described [16]. For automated processing of blood samples in the sample-processing module, 15ml-conical falcon tubes (Beckton-Dickinson, USA) were barcoded.…”

“…For automated processing of blood samples in the sample-processing module, 15ml-conical falcon tubes (Beckton-Dickinson, USA) were barcoded. Similarly, slides in the analysis module are tracked by barcoding high temperature glass slides as described previously [16].…”

“…Several others, Weber et al [14], Schunk et al [15], Martin et al [16], Romm et al [17], Garty et al [18] and Fenech et al [19], have described the need for automation of cytogenetic assays, such as DCA and/or CBMN (Cytokinesis-blocked micronucleus assay), in order to support medical management of accidentally exposed individuals. Here in this paper, we describe our progress in the automation of sample preparation and chromosome-aberration analysis and highlight important limitations and potential remedies for improving a laboratory's throughput to overcome important barriers in the potential application of cytognetic assays in radiation mass casualties for diagnostic dose assessment of ARS.…”

THE DECADE OF THE RABiT (2005–15)

“…To fulfill this need, the Columbia Center for High Throughput Minimally Invasive Radiation Biodosimetry, funded by NIAID (National Institute of Allergy and Infectious Diseases), began the development of the Rapid Automated Biodosimetry Tool (RABiT), as an end-to-end automated, ultrahigh throughput robotically-based biodosimetry workstation (2)(3)(4)(5)(6)(7) . Although different procedural steps involved in cytogenetic bioassays (from chromosome preparations (8) , to scoring (9) and sample tracking (10) ) had previously been automated, the RABiT is presumably the first end-to-end system developed thus far where the only human intervention with samples is at the sample collection step (11) and interpretation of the reported results by a qualified medical professional.…”

Application of the micronucleus assay performed by different scorers in case of large-scale radiation accidents

“…There is also a risk that the samples might not be collected under the controlled conditions or sample tracking and processing may be delayed [9]. Yet, there are no reported studies about possibilities to score MNi by people without any cytogenetic experience, which might enhance the process of dose assessment in case of radiation accidents.…”