The unmanned spacecraft, known as OSIRIS-REx, is poised to blast off at 7:05 pm (23:05 GMT) atop an Atlas V rocket in Cape Canaveral, Florida. The weather forecast is 80 percent favorable for liftoff.
The USD 800 million mission will travel for two years on a journey to Bennu, a near-Earth asteroid about the size of a small mountain.
The solar-powered spacecraft's main goal is to gather dirt and debris from the surface of the asteroid and return it to Earth by 2023 for further study.
But the mission should also shed light on how to find precious resources such as water and metals in asteroids, a field that has generated increasing interest worldwide.
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"We are going to map this brand new world that we have never seen before," said Dante Lauretta, OSIRIS-REx principal investigator with the University of Arizona, Tucson.
Using a suite of cameras, lasers and spectrometers, "we are really going to understand the distribution of materials across the surface of that asteroid," he added.
The spacecraft is expected to reach Bennu in August 2018 and spend two years studying it before it begins the sample collection attempt in July 2020.
NASA hopes OSIRIS-REx will bring back the largest payload of space samples since the Apollo era of the 1960s and 1970s, when American explorers collected and carried back to Earth some 360 kilograms of moon rocks.
The collection device, known as the Touch-and-Go Sample Acquisition Mechanism (TAGSAM), should pick up about two ounces (60 grams) from the asteroid, but in tests so far it has generally picked up five times that amount.
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