"Lab on a Chip” Improves Effectiveness of In Vitro Fertilization

A tiny microfluidic chip that evaluates the fitness of embryos harvested for in vitro fertilization (IVF) transfer could make the procedure faster, easier, and more effective than conventional embryo selection methods.

Researchers from the Massachusetts Institute of Technology (MIT; Cambridge, MA, USA) designed a microfluidic device, using multilayer soft-lithography, which performs microfluorometric enzymatic assays of several key energetic substrates (glucose, pyruvate, and lactate) in an automated fashion. Following manual loading of samples and enzyme cocktail reagents, the system performs sample and enzyme aliquotting, mixing of reagents, data acquisition, and data analysis, without operator intervention.

The system can perform serial measurements of glucose, pyruvate, and lactate in triplicate with submicroliter sample volumes within five minutes, and automated analysis of 10 samples with intermittent calibration over a three-hour period. With the use of a standard epifluorescent microscope and a charge coupled device (CCD) camera, linearity is obtained with metabolite concentrations in the low micromolar range (as low as femtomole levels of total analyte).

The system is designed to be inherently flexible, and is easily adapted for any nicotinamide adenine dinucleotide phosphate hydrogenase (NAD(P)H)-based assay and can be scaled up in terms of sample ports. Open source Java-based software allows for simple alterations in routine algorithms. Furthermore, the device can be used as a standalone device in which media samples are loaded, or alternatively can be integrated into microfluidic culture systems for in line, real-time metabolic evaluation. In laboratory studies, the researchers collected fluids surrounding 10 mouse embryos and added the fluids to the computer-controlled chip for analysis. They showed that the device quickly and accurately measured the nutrient content of the sample fluids. The device and the study were described in an article published in the September 1, 2008, issue of the journal Analytical Chemistry.

"With the improved throughput and flexibility of this system, many barriers to evaluating metabolism of embryos and single cells are eliminated,” noted lead investigator professor Todd Thorsen, Ph.D., and colleagues of the department of mechanical engineering. "As a proof of principle, metabolic activities of single murine embryos were evaluated using this device.”

The current method for evaluating an embryo's fitness for IVF involves microscopic examination of its physical characteristics, such as cell shape. However, these assays are performed manually using constriction pipets, which is time-consuming and unreliable procedure. Using the microfluidic chip, which is about the size of a coin, the health of embryos can be automatically analyzed before transplant by measuring how the embryo alters key nutrients in the tissue culture medium used to nurture them.

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Massachusetts Institute of Technology