When an astronaut training for a trip to Mars is mysteriously killed inside a Mars simulation, Castle and Beckett don spacesuits to investigate. But when they discover no one inside the sealed simulation could have committed the murder and no one from the outside could get in, the case takes a shocking turn.
When Castle is prentending to moon walk, the initial fanfare (titled "Sunrise" in the composer's programme notes) Also Sprach Zarathustra plays.
The mission computer MIRA is an AI that is interacted with via voice control, which Castle states is "a little 2001" and Dr. Rusham Haroun refers to as "more Siri than HAL".
The Castle and Beckett return home, Martha can be heard singing "Daisy Bell", the song that HAL sings as he is dying.
When Viggo Jansen asks MIRA to run a diagnostic, MIRA says "I'm sorry, I can't do that" a reference to the famous line "I'm sorry Dave, I'm afraid I can't do that".
When opens the vents, Castle yells for MIRA to "Open the pod-bay door". This is the same command that Dr. David Bowman is giving HAL when he refuses to comply.
Like HAL, MIRA came to believe that a human would compromise her mission.
Immediately after parodying the Star Trek opening voiceover, Castle and Beckett are let into Newton Endeavors by a security guard using the code "4747". Occurances of the number 47 have been inserted into the Star Trek series and movies since 1990 in dialogue, signs, and labels as an in-joke.