We welcome you to watch this webinar where you will experience presentations from top ranked scientists focused on the use of stable isotope standards in MS/MS screening.

August 17, 2022 11:00 AM - 12:30 PM EDT

 

Multiplexing Homocysteine into
FIA-MS/MS Primary-Tier Newborn
Screening by Selective Thiol Derivatization 

KostasKonstantinos Petritis, PhD | Laboratory Chief
 US Centers for Disease Control and Prevention (USA)

Abstract: Homocystinuria (HCU) results from the inability to convert homocysteine to cystathionine, due to enzymatic or vitamin B12 deficiencies, causing an elevation of total homocysteine (tHcy) in the blood and urine. Methionine is used as a primary-tier marker for HCU, but methionine concentrations physiologically vary in newborn blood which impacts false positive rates. Furthermore, in HCU patients, methionine concentrations may take a few days after birth to be elevated above cutoffs which leads to false negatives (dried blood spot collection takes place 24-48 hours after birth).  Here we present a breakthrough method to selectively derivatize the Hcy thiol function group to successfully multiplex tHcy into primary-tier assays with amino acids, acylcarnitines, succinylacetone, adenosine, deoxyadenosine, creatine, creatinine, and guanidinoacetic acid for analysis by FIA-MS/MS. 

During this webinar, you will learn about:

  • Mass spectrometry role in newborn screening expansion 
  • Current challenges with Homocystinuria detection in newborn screening 
  • Multiplexing of total homocysteine analysis in primary MS/MS newborn screening 

 

Improving the Efficiency of Internal Standard Preparation in Newborn Screening Using a Custom Isotope Premix

HeatherHeather Golsan, MSc | Director of Mass Spectrometry Operations
Utah Department of Health and Human Services (USA) 

Abstract: To improve the process efficiency and to minimize errors in the processing of newborn dried blood spot samples, isotopically labeled compounds are imperative and are procedurally inserted as internal standards. To facilitate targeted screening assays, the Utah newborn screening laboratory contracted a manufacturer to prepare a custom amino acid isotope mix. This dried down mix consists of three disorder-relevant amino acids that can be easily reconstituted in 1 mL of solvent, eliminating the need to weigh and dilute the individual compounds prior to use. The pre-formulated mix helped increase the throughput, accuracy, and reproducibility of internal standard preparation while maintaining the desired assay sensitivity. This presentation will discuss the analytical development and performance of the amino acid isotope mix in the context of newborn screening applications.

During this webinar, you will learn about:

  • Desired concentrations of isotopically labeled internal standard
    compounds are simple to request and obtain in the form of a custom mix from a compound manufacturer. 
  • Laboratory validation of a pre-weighed custom mix is easily achievable in a high throughput laboratory setting. 
  • Use of a custom mix when compared to standard weighing procedures is more streamline for a production workflow because it minimizes the preparation, training, and documentation requirements of the laboratory. 

 

Use of Stable Isotope-labelled NSK Mixes for Newborn Screening in the United Kingdom 

UllasUllas Joseph, MSc C(ASCP) | Chief Biomedical Scientist and Deputy Laboratory Manager
Sheffield Children’s Hospital (UK) 

Abstract: To be presented is an overview of how CIL’s NSK-A and NSK-B2-UK isotopically labelled mixes are used to screen metabolic conditions (e.g., PKU, MSUD, IVA, GA-1, MCAD, HCU) in the UK by tandem MS/MS. A summary of our complete pipeline will be described stepwise. This process includes ordering, validation, stock and internal standard preparation, analysis, result review, and reporting. An overview of the screening pathway (i.e., initial analysis, retest, follow-up sample analysis, and referrals) will also be discussed along with case examples from our NBS patient applications.

During this webinar, you will learn about: 

  • How NSK mixes can be used for Newborn Screening.
  • An overview of UK Newborn Screening.
  • Quick overview of follow-up tests in England. 

Thank you to all that attended our MS/MS Screening Webinar on August 17, 2022. We hope that you all enjoyed these presentations. For those that may have missed it, you can obtain the on-demand recording by using the link below.

Download On-Demand Recording

transcription

Biographies

Konstantinos Petritis, PhD | Laboratory Chief
US Centers for Disease Control and Prevention (USA)

Dr. Petritis received his MSc and PhD in Analytical Chemistry from the University of Orleans, France. In 2002, he joined Pacific Northwest National Laboratory, in Richland, WA, as a post-doctoral fellow and later as a senior staff scientist where he worked in the field of mass spectrometry based proteomics. In 2009, he was hired as an associate professor and laboratory head at the Translational Genomics Research Institute in Phoenix, AZ to work on biomarker development. In 2014, he joined the Arizona office of newborn screening and Phoenix Children’s Hospital as a principal investigator where he led several federal public health and research grants before joining CDC in June 2017. He has worked on bioanalytical mass spectrometry, biomarker development, automation, predictive algorithms and proteomic research. His current interests include but not limited to advanced analytical methods development and validation for newborn screening, development of dried blood spots based quality assurance materials and calibrators, clinical assays harmonization and metabolomics.  He has (co)authored more than 200 communications. 

Heather Golsan, MSc | Director of Mass Spectrometry Operations
Utah Department of Health and Human Services (USA) 

Heather Golsan (MSc) is a Microbiologist IV, Director of Mass Spectrometry Operations for the Utah Department of Health and Human Services. She has worked for the Utah Department of Health and Human Services for 3 years. She received a Bachelor of Science in Biomedical Sciences at Colorado State University in 2012 and a Master of Science in Laboratory Medicine and Biomedical Science at the University of Utah in 2019. 

Ullas Joseph, MSc C(ASCP) | Chief Biomedical Scientist and Deputy Laboratory Manager
Sheffield Children’s Hospital (UK) 

Ullas Joseph (ASCP) is the Chief Biomedical Scientist (2018 to present) at the Sheffield Newborn Screening laboratory, which is the second largest screening laboratory in the UK. Prior to this position, Ullas was a Senior Biomedical Scientist in the same laboratory from October 2015 to September 2018. Ullas holds a BSc degree in Zoology and a MSc in Microbiology. He is also qualified as Biomedical Scientist after obtaining a Graduate Certificate in Biomedical Science (2011). Ullas specialised in Clinical Chemistry from IBMS London in 2014 and is recognised as a Registered Scientist by the British Science Council. Ullas completed leadership and management qualification in 2015 and is now certified as C(ASCP) by ASCP.