Advanced robotic workstations aid pioneering child DNA study

1st April 2013

Dr Bill Bradbury reports on the implementation of two special robotic workstations to help maintain and analyse the DNA.

The implementation of two special robotic workstations in the new DNA bank and Population Genetics laboratory that has been built in the shell of the old Bristol Children's Hospital (UK) has been announced by Tecan UK.

Serving the aChildren of the 90s' project based at the University of Bristol, the two robotic systems have been designed to help maintain and analyse the DNA from the 10000 children and mothers who have donated more than half a million biological samples to the project since 1991-2.

No other study in the world has such a large DNA collection from a normal population. The project aims to work out the interplay between genetic and non-genetic influences on the growth and development of normal children from the womb into adult life. Through gaining an understanding of these influences the Bristol researchers aim to discover new ways of preventing and treating disease.

As part of the programme at Bristol cell samples are held in long-term storage for future experimentation.The study was designed from its inception to allow the exploration of how common variations in our genetic makeup influence health outcomes in childhood and adult life. To ensure an abundant supply of DNA, the study was funded by the Wellcome Trust to create an immortalised cell-line from blood samples given by each cohort member. Normal blood cells have a limited life-span, but they can be atransformed' by a virus under laboratory conditions so that the resulting cell-lines grow indefinitely. The process of transformation is normally very labour intensive and robotic automation was seen as the key to allowing the high throughputs required creating up to 25000 cell-lines in a five year period. If the cells are left on their own they will eventually die, so at regular intervals the cell culture media has to be changed and replaced with fresh culture to encourage cell replication.

A robotic workstation has been built by Tecan for this purpose that automates the storage of samples. Growing cultures in multiwell plates are held in automated incubators and delivered via shuttles to a Tecan Genesis robot housed in an air-flow cabinet. Lids are removed at the workstation, and the liquid handling system allows manipulation of the culture according to a worklist previously generated by the laboratory staff's evaluation of each culture. Spent medium can be removed and replaced with fresh medium, typically at early phases of the transformation process, or, when the culture is established, the culture can be divided and distributed across increasing numbers of wells, with the addition of fresh medium, until the plate is filled with growing cells. After transfer to a flask the culture is ready to be harvested for long-term storage in liquid nitrogen and for DNA extraction. For each culture this process takes about six weeks, with visits to the robot every two or three days. The system is designed to allow up to three hundred cultures to be processed over a 12 hour period. High capacity incubators, transfer the samples from the incubators to the workstation and provides the liquid handling to remove the old media and provide the new. All these operations are carried out in sterile conditions to avoid contamination of the samples.

The second Tecan robotic workstation extracts, orders and delivers processed extracted DNA samples for genetic analysis by research scientists. Extracted DNA samples are at a wide range of concentrations depending on the state of the sample from which DNA was extracted. To ensure that the optimal conditions for subsequent genetic analysis are met, the system normalises the DNA concentrations, and generates multiple sealed daughter plates ready for analysis by scientific collaborators. The system also features a 'pick and place' arm capable of cherry picking minitubes from closely packed 96-position racks. The workstation can, on a request from a scientist, pick out the sample tubes of interest according to any chosen variable (for example: male or female; empty or full, etc) from the store and reorganise them. The system performs this task with a speed and accuracy, which would be almost impossible to achieve manually.

Saving the need for an operator to manually search through to find them. In addition as DNA concentration of new samples is likely to vary considerably, due to variance in the original source and purification method, the workstation will also anormalise' the DNA samples as part of their preparation for storage.

The robots and new laboratories mark an important new phase for Children of the 90's - also known as the Avon Longitudinal Study of Parents and Children (ALSPAC) ­ in their search for to discovering new ways of understanding, preventing, and treating disease.

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Dr Bill Bradbury is a consultant working with Tecan who are based in Theale, UK.





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