After finding a species of the Higgs boson, CERN scientists are now seeking dark matter at the Large Hadron Collider (LHC).
A race is on between groups at the LHC, the world's biggest particle accelerator, and other scientists operating in space and deep underground who are chasing the same discovery.
Dark matter is invisible "stuff" that holds galaxies together with gravitational glue but defies common sense by being undetectable by any direct means.
It is thought to make up around a quarter of the mass-energy in the universe.
Finding it would be a major coup second only to detecting the Higgs boson, the elementary particle believed to be responsible for mass.
It will be a top priority when a revamped and almost twice as powerful LHC is switched back on in March 2015 after a two-year shut down and refit.
The £2.6 billion machine fills a 27 kilometre (17 mile) circular underground tunnel that straddles the border of France and Switzerland near Geneva.
Protons - the hearts of atoms - fired in opposite directions around the tunnel at just under the speed of light are smashed together at enormous energies, simulating conditions that occurred an instant after the Big Bang.
Scientists hope to create new particles out of the fire balls at four detector points placed around the LHC ring.
Before the shut down, the LHC reached a record-breaking energy level of eight trillion electrovolts (8 Tev). After the upgrade, this will be boosted to 14 Tev.
As energy is converted to matter, higher energies allow heavier and more exotic particles to be created.
One of them could turn out to be a weakly interacting massive particle, or Wimp - the leading candidate for dark matter.
Dr David Newbold, from the University of Bristol, a member of the CMS (Compact Muon Solenoid) detector experiment at the LHC, said: "There's a real conflict between astronomy, which says dark matter is there, and particle physics, which hasn't found anything yet.
"This has been the big surprise, Nature's failure to put dark matter in a place where we can find it."
The pressure is on the LHC scientists after possible signs of dark matter emerged from a laboratory buried 2,600 feet underground in an American mine.
Researchers from the Cryogenic Dark Matter Search (CDMS) in Minnesota are trying to detect dark matter particles clashing with the nuclei of normal Earthly atoms.
Earlier this week they reported three signals that could indicate Wimp particle collisions, but the evidence is a long way from being confirmed.
One puzzle is that the data suggest Wimps are much lighter than had been thought, in which case they should already have been produced at the LHC or another accelerator facility.
Earlier this month, a team operating a £1.32 billion particle detector attached to the International Space Station announced that it had found a potential "smoking gun" of dark matter.
The Alpha Magnetic Spectrometer (AMS) spotted positrons - antimatter electrons - that could have been emitted by Wimp particle collisions far away in space.
"There's a bit of a race on," said Dr Newbold, speaking at CERN, the European Centre for Nuclear Research where the LHC is located.
"It's possible that we could see a direct signature of dark matter from one of these experiments before you see it in the LHC.
"But the CDMS result isn't conclusive and the AMS needs more data."
Colleague Professor Jon Butterworth, from University College London, who works on the giant Atlas detector, said: "When we go up in energy from 8 Tev to 14 Tev I'd say there's a 50/50 chance of finding dark matter. There's a slim chance that dark matter might be hiding in the data we've got now.
"I think dark matter is the most important thing as far as my experiment is concerned.
"People are very excited about this, and have been for a while.
"We are on the edges of knowledge here and the nature of dark matter is a big question. I hope we'll be able to answer it in the next few years."
Dark matter is closely tied up with the concept of supersymmetry, an extension of the Standard Model theory that explains the functions of elementary particles.
Supersymmetry proposes that every known particle should have a heavier twin. Many scientists believe dark matter consists of these supersymmetry partners, and are hoping to be proved right.
However, finding such a particle would just be the beginning.
"We're talking about the simplest kind of supersymmetry," said Dr Newbold.
"There are theories that conjure up the possibility of multiple dark matter particles.
"The properties of dark matter, how many kinds of dark matter there are - all this is science yet to come."
Dark matter is now believed to make up around 26 per cent of the universe and "normal" matter just 4 per cent.
Dark energy - a mysterious force causing galaxies to hurtle apart at accelerating speed - is thought to account for the remaining 70 per cent.