96-well Pipetting for Early Disease Identification
Researchers have recently developed a more accurate method of identifying certain lysosomal storage diseases in newborns. The Rainin Liquidator 96 speeds up sample preparation and ensures high accuracy in the diagnosis of these genetic diseases.
Lysosomal storage diseases (LSD) are a family of disorders with mild to severely debilitating symptoms. These diseases are usually caused by the mutation of proteins that are involved in lysosomal processing. The severity of symptoms depends on which proteins are mutated, how they are mutated, different factors controlling gene expression and environmental factors. There is often a delay in the diagnosis and treatment of LSDs due to their variable presentation and non-specific symptoms.
Diagnosing LSD with tandem mass spectroscopy
In a paper submitted to The Journal of Pediatrics, entitled “Identification of Infants at Risk for Developing Fabry, Pompe or Mucopolysaccharidosis-I from Newborn Blood Spots by Tandem Mass Spectrometry” by Scott et al., the authors developed a method that uses mass spectrometry to screen for many LSD in parallel. They first took dried blood spots from newborns, in which many lysosomal enzymes retain activity, and re-suspended them in a buffer containing the appropriate enzyme substrates for the enzymes whose defects cause the diseases. Using tandem mass spectrometry, the team could distinguish whether a given infant was deficient in any particular enzyme activity. Depending on the enzyme activity in a given blood spot, the authors analyzed the gene sequences of the newborns to confirm whether low enzyme activity measured in the assay correlated with mutations in the same enzyme. Scott et al. found that their method increased the likelihood for the detection of Fabry, Pompe and mucopolysaccharidosis-I over that of standard clinical diagnosis.
Liquidator 96 – the instrument of choice
The experiments required the analysis of more than 100,000 blood spots. Such a high number of samples required an accurate and systematic sample preparation process. Small ‘punches’ of each blood spot were placed in a 96-well plate. Using METTLER TOLEDO’s Liquidator 96, the researchers were able to add enzymatic reaction solution, reaction quench and product extraction solvents to the plate rapidly and accurately. These samples were then used for tandem mass spectrometry.
The Liquidator 96 is a highly accurate and precise benchtop 96-well pipetting instrument that does not require any electricity for operation. With 96-channels pipetting at the same time, the Liquidator 96 can significantly accelerate experimental workflows beyond what is possible with single and multichannel pipettes. In time-critical applications, like enzymatic reactions, it is especially important that the reaction is started in all 96-wells at the same time. Liquidator carries out this task simply and accurately and avoids the risk of skipped rows, a common scenario with multichannel pipetting in 96-well plates.