(A) Blood samples with different characters. Whole blood is the raw material for DBS preparation by stabilization and homogenization. A whole spot is a 12-mm diameter circle of dried whole blood with a volume of 50 μL taken from the filter paper (DBS card) by scissors. A disc is approximately a 3-mm diameter circle of dried blood taken from a whole spot by a paper puncher, and the remainder is the remaining part of the whole spot after removing all discs. A maximum of six discs were punched out from specific locations as numbered. (B) Precut mass defined (3 × 4 cm) paper for DBS preparation with various sampling volumes from 0 to 100 μL. Three discs were punched out from each DBS sample in the same position, and one disc each was taken from the 0 and 10 μL DBS samples.
Measured values of the six AAs from whole blood, whole spot sampling, and disc sampling. For the latter, two discs from the center of the spot and from the edge of the spot were separately measured. The white bars represent whole blood samples, the black bars are whole spot DBS samples, the gray bars and black-patterned bars are the disc samples in different positions (center and edge), and the light gray-patterned bars are the remainder DBS samples.
Results comparisons of DBS CRMs and commercial quality control materials in three laboratories including two clinical testing laboratories. All disc sampling used a nominal disc size of 3-mm diameter. (A) Ratio yield of the measured values between whole spot DBS sampling and disc DBS sampling. L and H denote the low and high samples of the DBS CRMs, respectively. (B) Recovery of the measured values to the reference values by manufacturer’s claim. KRISS was the coordinating lab of this study, and the two clinical testing laboratories were coded as Lab A and Lab B.
Newswise — As baby underwent a newborn screening test for inherited metabolic disorders within seven days of birth. The test checks for risk factors such as hypothyroidism, phenylketonuria, maple syrup urine disease, which can lead to developmental disabilities if not detected in their early stage. Every year, one in every 1,000 newborns are diagnosed with inherited metabolic disorders.
The Korea Research Institute of Standards and Science (KRISS, President Hyun-Min Park) has developed Certified Reference Materials (CRMs)* that can enhance the reliability of using dried blood spot testing for newborn screening.
* CRM: A reference material that serves as a standard in determining the accuracy of measurements and analytical methods
DBS is a sample obtained by drying a drop of blood from the finger or heel on a piece of filter paper. This approach is used for screening rather than actual diagnosis, as it is less accurate than venous blood sample tests. Its common applications include newborn screening for inherited metabolic disorders and doping control during Olympics.
The proposed CRM provides eight certified values and 10 reference values for amino acids, glucose, galactose, and acylcarnitines, which are diagnostic markers of inherited metabolic disorders in newborns. This allows accurate measurement of the amount of target compounds in the DBS.
The lack of reference values has made it difficult for DBS testing to be considered reliable for medical decision. In addition, there has been a problem with measurement bias caused by the need to retrieve portions of blood spots using a paper puncher.
The KRISS Biodiagnostics Analysis Team found that a 0.4 mm bias in diameter led to a 0.78 μL (one millionth of a liter) difference in sample volume.
The research team controlled the sample volume to 50 μL during the CRM manufacturing stage, and proposed bias-free measurements as certified values, thereby successfully creating CRMs with complete measurement traceability to the International System of Units. This is the first-ever development of DBS CRMs.
Dr. Ji-Seon Jeong, a principal researcher at KRISS, said, “DBS has come under the spotlight as a convenient way of blood sampling, which satisfies the high demand for remote healthcare and home sampling in the days of the pandemic. Our study has laid the foundation to improve the reliability in DBS sample measurement, opening the door for DBS to become an effective tool not only in screening but also diagnosis.”
KRISS plans to develop more CRMs for other diagnostic markers used in newborn screening.
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As the representative institute in the national measurement standards, the Korea Research Institute of Standards and Science (KRISS) has been setting the highest measurement standards and ensuring their international equivalence since its inception in 1975. Thereby, we help build solid foundations for the national development in science and technology and for industrial advancements
Funded by KRISS, the study was published in the world-leading journal Analytical Chemistry (IF: 8.008) in July.
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Credit: Korea Research Institute of Standards and Science (KRISS)
Caption: (A) Blood samples with different characters. Whole blood is the raw material for DBS preparation by stabilization and homogenization. A whole spot is a 12-mm diameter circle of dried whole blood with a volume of 50 μL taken from the filter paper (DBS card) by scissors. A disc is approximately a 3-mm diameter circle of dried blood taken from a whole spot by a paper puncher, and the remainder is the remaining part of the whole spot after removing all discs. A maximum of six discs were punched out from specific locations as numbered. (B) Precut mass defined (3 × 4 cm) paper for DBS preparation with various sampling volumes from 0 to 100 μL. Three discs were punched out from each DBS sample in the same position, and one disc each was taken from the 0 and 10 μL DBS samples.
Credit: Korea Research Institute of Standards and Science (KRISS)
Caption: Measured values of the six AAs from whole blood, whole spot sampling, and disc sampling. For the latter, two discs from the center of the spot and from the edge of the spot were separately measured. The white bars represent whole blood samples, the black bars are whole spot DBS samples, the gray bars and black-patterned bars are the disc samples in different positions (center and edge), and the light gray-patterned bars are the remainder DBS samples.
Credit: Korea Research Institute of Standards and Science (KRISS)
Caption: Results comparisons of DBS CRMs and commercial quality control materials in three laboratories including two clinical testing laboratories. All disc sampling used a nominal disc size of 3-mm diameter. (A) Ratio yield of the measured values between whole spot DBS sampling and disc DBS sampling. L and H denote the low and high samples of the DBS CRMs, respectively. (B) Recovery of the measured values to the reference values by manufacturer’s claim. KRISS was the coordinating lab of this study, and the two clinical testing laboratories were coded as Lab A and Lab B.
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