April 1, 2008 (Vol. 28, No. 7)

Molecular Biometrics Uses NIR Spectroscopy to Detect Embryo Viability by Creating Metabolic Profiles
While viewing an exhibit of Monet’s impressionistic paintings, Jim Posillico, Ph.D., president and CEO at Molecular Biometrics in Chester, NJ, noted the similarity of the art with his company’s metabolomics platform.

Like the discrete brush strokes, textures, and colors that interact to form an impressionistic image, “metabolomics looks at the bigger picture from its constituent parts,” Dr. Posillico explains. The individual pieces of information in metabolomics are molecular biomarkers in biological samples, which give an accurate diagnostic profile of a biological condition or state of cellular activity.

The technology platform at Molecular Biometrics combines metabolomics with near infrared (NIR) spectroscopy. The company’s lead product, ViaTest-E™, tests the viability of embryos at in vitro fertilization (IVF) clinics to increase the chance for a successful pregnancy. The test uses NIR spectroscopy to detect biomarkers of oxidative metabolism that strongly correlate with embryo viability.

The groundwork for the company’s biospectroscopy-based metabolomics platform was done in the laboratory of chemist David Burns, Ph.D., at McGill University in Montreal, Quebec. Dr. Burns and Dr. Posillico, an endocrinologist, cofounded Molecular Biometrics in 2005 and licensed five broad patents from McGill University, which cover applications of metabolomics and different forms of spectroscopy to different medical conditions including fetal development and neurodegenerative diseases like Alzheimer’s and Parkinson’s.

IVF Improvement

The company invented a prototype instrument, about the size of a toaster, for use at IVF clinics. After confirming that NIR is as sensitive as NMR or Raman spectroscopy for identifying and quantifying biomarkers, the company selected NIR because it is affordable and does not require much technical know-how to operate, reports Dr. Posillico.

The NIR instrument produces a metabolomic profile of the target biomarkers in a biological specimen. For IVF, the analysis requires just seven microliters of the sample media bathing the embryonic cells and gives results in about one minute, according to Dr. Posillico. The test is entirely noninvasive, and embryos are never harmed.

The instrument has no moving parts, other than a cooling fan and light bulb that needs periodic replacement. A technician loads a sample into a disposable sample cell, places it in the instrument, and presses a button. The results are displayed as a numerical viability score based on calculations using proprietary algorithms. The test can be readily incorporated into the IVF procedure, reports Dr. Posillico.

The method is intended to work in conjunction with subjective microscopic morphological assessments, which due to poor predictive value, require the implantation of three to five embryos to improve the odds of pregnancy. This practice of multiple embryo transfer, however, raises the risk for multiple births as well as increasing healthcare costs. “The high incidence of multiple gestations is the black cloud hanging over the field of IVF,” says Dr. Posillico. To make IVF even more successful, the NIR technology is being extended to the assessment of viable oocytes and semen prior to fertilization, he reports.

The average infertile couple undergoes three cycles of IVF treatment while trying to become pregnant. Embryologists currently have no reliable biological ways to distinguish viable and nonviable embryos, and only about 15% of embryos transferred in IVF result in pregnancy. “We hope to reduce the number of cycles needed to achieve pregnancy by increasing the efficiency of picking viable embryos that have the highest chance of resulting in pregnancy,” explains Dr. Posillico.

The product will first be launched in Japan, Australia, and Europe, followed by the U.S., which has 425 IVF programs. The company recently completed a large clinical trial of 1,800 women at centers in Europe, Japan, Australia, and the U.S. that validated the specificity, selectivity, and utility of the ViaTest-E in IVF, according to the company. Dr. Posillico is working with the FDA to move forward with a pivotal trial to clear the way to marketing the NIR instrument.

Multiple Applications

By monitoring different biomarkers and modifying algorithms, the NIR instrument also detects biomarkers of oxidative metabolism in blood plasma samples from patients with Parkinson’s and Alzheimer’s disease. “The beauty of our technology is that you don’t have to invent a different instrument to measure a different disease state,” Dr. Posillico adds.

Not only can the NIR method distinguish unique biomarker profiles for different neurological diseases, but these profiles are also distinctly different from those of healthy, age-matched controls, notes Dr. Posillico. There are no proven biomarkers for Parkinson’s, and two clinically useful biomarkers for Alzheimer’s need spinal fluid samples. “Our test only requires a finger prick to get seven microliters of plasma,” he reports.

The information obtained from NIR could be used for the early detection of neurodegenerative disorders or to monitor the efficacy of drugs on the market or in development, explains Dr. Posillico. Patients with Alzheimer’s and Parkinson’s take powerful drugs for years, yet there are few biological metrics for measuring how long-term treatment affects patients. “The potential application of our technology platform to drug discovery and development is very high,” he says.

Another application of the NIR technology is for lactic acid (lactate) monitoring, which is replacing complicated measurements of blood gases and enzymes in critical-care units and emergency and operating rooms. “Lactate is viewed as a first-line indicator of a patient’s metabolic state and general health,” explains Dr. Posillico, but a blood sample must be drawn and sent to a laboratory for analysis. Molecular Biometrics is testing a noninvasive finger cuff monitor, similar to ones used in pulse oximetry.

Products for monitoring neurodegenerative diseases, preterm labor, and lactate status are in the pipeline, but it will take more money to develop and market these products. “We saw a more straightforward opportunity to enter the IVF market first with our platform,” Dr. Posillico says, “then we’ll build other disease applications.”

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