During Master Chief's introduction, his hands are clearly shaking, and he takes a moment to compose himself before putting on his helmet. It drives home the fact that John at this point is on the point of breaking, yet spends the rest of the game being The Stoic. The man is probably screaming inside but puts up a stoic front to hide his true feelings.
Even the other members of Blue Team can tell that he's clearly not okay:
Fred-104: I haven't seen Chief push himself this hard since we were in boot camp. Kelly-087: He's fine, Fred. Fred-104: This many missions non-stop isn't "fine".
What's even more heartwrenching is Fred's second line. Chief's clearly not doing well at all, and to cope with the events of Halo 4, he's been going on mission after mission without rest just to keep himself busy.
Buck having to hunt down Master Chief, whom he has always looked up to, and there's Reality Subtext as Nathan Fillion has been a major Halo fan from the start, and it shows on his face. Even sadder is Locke, who is committed to the mission, no matter what, but every so often it's clear he's not a fan of having to hunt him down either.
Locke: "...You're not the only one who's here because of him."
This is probably why Buck didn't get involved in the fight between Locke and the Master Chief: he didn't know who he would help.
While hunting him, you'll notice that Locke never calls his quarry "Master Chief" or "John". It's always a number (117), as a way of maintaining an emotional distance from his job, and also to avoid having to call him by his name or rank/nickname.
Then you have Catherine Halsey, who is normally an Ice Queen, begging Locke to bring Chief home. The fact she sounds like a mother pining for her baby who is in mortal danger is not a coincidence.
The page image comes from the closing of Chapter 14 when it becomes clear as day that there's no way Master Chief is going to go along with Cortana's vision of a "perfect ordered galaxy". Cortana appears to him in full form, and it becomes obvious that she's in love with him, and she will never kill him. She'll just put him in suspended animation til her plans are over. The complex emotions playing on her face are heartbreaking. The fact is she is a woman who's been rejected by someone she now considers her lover.
And let's not forget what poor Chief must be feeling about all this. Even after all Cortana had done he was still trying to get her to stand down peacefully and come home. And yet he could not convince her. The music just makes the whole scene even more heart wrenching.
It's also sad to see how HUGE a parallel it is to the situation with the Librarian and Ur-Didact, both who serve as counterpoints to Chief and Cortana. Only this time the situation is reversed, with the female counterpart sealing away the male.
Or what Halsey is thinking. She knows what Cortana wants to do and its putting her favorite protegee in danger. And worst of all? It's her own personality, face and voice that's doing it.
All this could have been averted if John had been there when she grew into the mantle. Remember back in Halo: Combat Evolved when she started to lose it after being connected to the Halo's control room and John calmed her down? They protect each other from the universe, and sometimes themselves.
During their conversation, Cortana claims that she will be making people more than they are. John compares this to what Dr. Halsey did to him. The context makes it clear that he doesn't consider this a good thing, making it a rare moment where he seems regretful of his life. And even though he still respects Halsey, he's not blind to the terrible things that she did in the name of the greater good.
When Cortana surprises Blue Team by holding them in a Cryptum, Master Chief is helpless. The One-Man Army who has saved the galaxy is watching Cortana walk away and all he can do is reach out his hand and say her name, clearly a last ditch attempt to beg her to come back with him.
Evelyn Collins, who broadcasts a heartbreaking message as she breaks down, whilst Fireteam Osiris makes their way up the space elevator of Meridian in order to escape the newly-awoken Guardian:
"Hello? Can anyone hear me? I'm at Meridian station. Everyone is dead. Governor Sloan isn't here, I... Please? Is there anyone left here but me?!"
Despite the fact that John going with her would in no way be a good thing, Cortana's anguish at John and Blue Team being taken from her by Exuberant Witness can tug at your heartstrings because she really cares about John and wants to spare him the horror of what she's planning.
