January 1, 2006 (Vol. 26, No. 1)
Maine Molecular Quality Controls Targets a Rapidly Growing Biotechnology Market
Joan Gordon and Clark Rundell, Ph.D., know the importance of controls in clinical laboratory testing, having both worked in the clinical laboratory at the Maine Medical Center in Portland, the state’s largest healthcare facility.
When running a batch of patient samples to measure glucose levels, for example, a technologist adds controls with known levels of glucose to make certain that the analyzer is working properly. However, the growing field of molecular diagnostics, which screens for genetic markers, has few such controls.
So Gordon, president and CEO, and Dr. Rundell, vp of research, formed Maine Molecular Quality Controls (MMQCI; www.mmqci.com) in Scarborough, Maine to pursue the development of molecular control products.
Joan Gordon and Clark Rundell, Ph.D., know the importance of controls in clinical laboratory testing, having both worked in the clinical laboratory at the Maine Medical Center in Portland, the state’s largest healthcare facility.
When running a batch of patient samples to measure glucose levels, for example, a technologist adds controls with known levels of glucose to make certain that the analyzer is working properly. However, the growing field of molecular diagnostics, which screens for genetic markers, has few such controls.
So Gordon, president and CEO, and Dr. Rundell, vp of research, formed Maine Molecular Quality Controls (MMQCI; www.mmqci.com) in Scarborough, Maine to pursue the development of molecular control products.
Joan Gordon and Clark Rundell, Ph.D., know the importance of controls in clinical laboratory testing, having both worked in the clinical laboratory at the Maine Medical Center in Portland, the state’s largest healthcare facility.
When running a batch of patient samples to measure glucose levels, for example, a technologist adds controls with known levels of glucose to make certain that the analyzer is working properly. However, the growing field of molecular diagnostics, which screens for genetic markers, has few such controls.
So Gordon, president and CEO, and Dr. Rundell, vp of research, formed Maine Molecular Quality Controls (MMQCI; www.mmqci.com) in Scarborough, Maine to pursue the development of molecular control products.
Joan Gordon and Clark Rundell, Ph.D., know the importance of controls in clinical laboratory testing, having both worked in the clinical laboratory at the Maine Medical Center in Portland, the state’s largest healthcare facility.
When running a batch of patient samples to measure glucose levels, for example, a technologist adds controls with known levels of glucose to make certain that the analyzer is working properly. However, the growing field of molecular diagnostics, which screens for genetic markers, has few such controls.
So Gordon, president and CEO, and Dr. Rundell, vp of research, formed Maine Molecular Quality Controls (MMQCI; www.mmqci.com) in Scarborough, Maine to pursue the development of molecular control products.
Joan Gordon and Clark Rundell, Ph.D., know the importance of controls in clinical laboratory testing, having both worked in the clinical laboratory at the Maine Medical Center in Portland, the state’s largest healthcare facility.
When running a batch of patient samples to measure glucose levels, for example, a technologist adds controls with known levels of glucose to make certain that the analyzer is working properly. However, the growing field of molecular diagnostics, which screens for genetic markers, has few such controls.
So Gordon, president and CEO, and Dr. Rundell, vp of research, formed Maine Molecular Quality Controls (MMQCI; www.mmqci.com) in Scarborough, Maine to pursue the development of molecular control products.
Cystic Fibrosis
Controls for molecular diagnostic testing, such as gene mutations linked to cystic fibrosis (CF), are where clinical immunology testing was 15 years ago, according to Gordon. The first tests for IgE or allergy RAST panels used samples from previous patients with known values. Now there are many quality control immunology standards with reproducible lot-to-lot characteristics. “New segments of laboratory medicine need time to mature and produce good controls,” says Gordon.
Molecular diagnostic tools have originated largely from academic laboratories, where researchers may not understand the need for clinical controls. In CF testing, one of the most common types of molecular diagnostic screenings performed, laboratories use samples from patients with known mutations as a control.
“We were surprised that no molecular diagnostic controls existed,” says Gordon. That spurred the scientists to invent and patent a process that uses synthetic chemistry to construct DNA standards with known mutations.
In the case of CF, at least 23 mutations in the CF transmembrane conductance regulator (CFTR) gene are recommended for testing for the disease. “Many are rare, so many laboratories don’t even have patient samples covering each mutation,” claims Gordon. The current protocol at clinical laboratories consists of running a control sample with the most common mutation plus one or two other patient samples with other mutations, on a rotating basis.
The synthetic DNA constructs available from MMQCI for CF improve on this practice. They contain 38 CFTR exon and intron sequences, so “all important mutations are covered in one control,” states Gordon. This ensures that any combination of mutations can be detected accurately and reproducibly.
The constructs are large, synthetic pieces of DNA that are inserted into plasmids and stored in the freezer. The controls are produced by combining synthetic DNA with a matrix that stabilizes the DNA, yet allows it to be extracted by common clinical methods. The researchers at MMQCI started with normal DNA, then added known mutations using in-vitro techniques. The methods developed at MMQCI can also mimic alleles or genomic DNA to detect homozygote or heterozygote states.
The complete CF control kit, sold as INTROL Cystic Fibrosis Panel I Control, contains three bottles with different combinations of CFTR mutations, polymorphisms, and wild-type sequences. “The best laboratory practice is to monitor all mutations in every run,” says Gordon.
CF testing is expected to grow, since recent studies show that babies born with CF benefit from immediate physical and nutritional therapies, and carrier screening for CF assists in family planning. The American College of Obstetricians and Gynecologists recommends screening of all pregnant women, and some states have mandated such testing for newborns. “We’re heading toward screening all pregnant couples and newborns, so we need better controls,” says Gordon.
Thrombosis
Another product, INTROL TRC Genotype Control, detects mutations in Factor II (prothrombin) and Factor V Leiden, which are the most common genetic risk factors for thrombosis. Each bottle of TRC Genotype Control contains two synthetic alleles of Factor II DNA and two synthetic alleles of Factor V DNA, suspended in a non-infectious, blood-like matrix.
Each allele contains a segment of the Factor II gene or a segment of the Factor V gene and carry either a mutation (Factor II G20210A or Factor V Leiden G1691A) or wild-type DNA. The alleles have been carefully mixed to produce three bottles containing three different genotypes of wild-type, heterozygous, or homozygous mutants.
The INTROL MTHFR Genotype Control measures methylenetetrahydrofolate reductase (MTHFR) gene mutations, C677T and A1298C, which are associated with thrombosis, cancer, leukemia, neural tube defects, cardiovascular disease, schizophrenia, and Alzheimer’s disease. Each bottle of MTHFR Genotype Control also contains two synthetic alleles of MTHFR DNA with different mutations and wild-type DNA.
MMQCI launched these three products in July. It also works with manufacturers of molecular diagnostic platforms to create quality control materials to test products during development.
Down the Line
Next in the pipeline at MMQCI are molecular diagnostic controls for infectious diseases and some cancers. All will be sequence-based, such as chromosomal translocations that characterize some types of leukemia. “We’ll cut and paste constructs to mimic the disease state,” explains Gordon. The infectious disease products will screen for the presence of RNA or DNA in diseases, such as HIV and hepatitis C, where “there’s a large repetitive market and early adaptation to molecular techniques,” states Gordon.
Synthetic molecular diagnostic controls also lend themselves to respiratory viruses that are difficult to culture and highly infectious microorganisms, such as tuberculosis (TB). “You don’t want medical technologists handling TB, and viral controls are difficult to grow,” says Gordon.
