The 2nd time, we have much more freedom in what to do and what to use.
If you weren't able to defeat some bosses without getting hit, then this is not the time for those attempts, as we will increase the difficulty to obtain our second boss stem cell. Here's the route we will take this time:
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Prisoners' Quarters - Toxic Sewers - Ramparts - Black Bridge - Still Village - Forgotten Sepulcher - Clock Room - Derelict Distillery - Throne Room
I will also point out which upgrades you should get in this run. If you can't afford all of them due to insufficient cells, don't worry. Not all of them are essential, but it's better to have them. You will also have the opportunity to unlock these in your next run. Health Flask III has a requirement of unlocking 10 items previously, so you might need to buy some inexpensive weapons to fulfill this prerequisite. Another useful tip you might have noticed is that at the Collector, you can always check how many more unlockables are needed for an upgrade. Based on all of this, you should purchase the following upgrades in this run:
Recycling II
Health Flask III
Gold Reserves III
Once you're ready, go right and collect the bags. These bags will contain some gold (the amount depends on your gold reserve upgrades at the collector) and your unspent cells from your previous run. As you proceed to the right, you'll see a large glass tube that you can interact with. In this tube, you can activate the obtained boss stem cells for higher difficulties, which we will do now. By activating the first boss stem cell, you'll see in a window the changes that occur in that run. Enemies will be slightly stronger, health refill fountains will only be available at every other passage, those without health fountains will have one health flask, the legendary forge cap will be improved, and doors from Prison Depths to Toxic Sewers and from Corrupted Prison to Ramparts will open. Also, the early phases of bosses will change, but nothing crucial. As for your equipment, you should have something similar to our first run, but this time you're free to choose anything as your secondary weapon (instead of the starter sword).
An important note about Boss Stem Cell (BSC) difficulties: Each activated boss stem cell has an advantage that comes in the form of new accessible areas. These areas can be entered through previously closed doors in biomes. Each of these doors is marked with the required number of Boss Stem Cells that must be activated in your current run to enter. At 1BSC, you'll only find a few more open doors in the biomes, but as you activate more BSCs, you'll gain access to more doors, more vendors, more loot, and even alternative route options that were previously impossible.
With everything set up, collect the weapons, and I advise you to speedrun this area, collecting the two scrolls on the way if you can (don't worry if you leave one or both behind). Head to the toxic sewers as quickly as you can, keeping in mind to get there within 2 minutes. Once you've reached the exit, you'll be able to interact with the corpse on the ground for some loot. When you're ready, exit through the doorway to the Toxic Sewers.
Since you managed to do it in under 2 minutes, you'll gain access to a bonus door, unlocking an achievement:
- ¡Arriba, arriba! ¡Ándale, ándale!
Open your first timed door.
Inside, collect everything, then go back to the main hall. You can buy any of the upgrades I suggested before, or you can save up the cells for the forge later, which can increase the quality of the items you find. Anyway, head to the right. If you've purchased any of the Recycling upgrades (highly recommended as soon as possible), you can recycle the health flask on the way before you leave for the Toxic Sewers, where you'll earn another achievement:
- What's that funky smell?
Reach the Toxic Sewers for the first time.
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As I mentioned before, I recommend that you complete the kill bonus every time you can, because it's an easy bonus for every passage. More loot means more opportunities to have the best possible gear.
Once you're here, you'll need to explore everything you can. At some point, you'll automatically see a cutscene where your character speaks to a prisoner who lost his rune. You, of course, are willing to help him. Eventually, you'll come across a pit, and this prisoner will call down from his cell, telling you that the rune is down in the pit. After you've jumped down, you'll have to defeat an elite Slasher. Once defeated, you'll obtain the teleportation rune and earn an achievement tied to obtaining it:
- What are you rubbing at anyway?
Absorb the Teleportation rune.
3 guides
A note for "The Queen and the Sea" DLC owners:
There is a giant fisherman you can talk to. Definitely speak with him, and he'll guide you on where to go and how to access the content of this DLC. I'll provide you with all the necessary information for these runs, both in the main text and on their respective pages.
If you're ready, leave this biome and proceed to the Ramparts.
Progress through the upcoming biomes as usual. After the Black Bridge, you will have the opportunity to spend all your cells at the Legendary Forge or on the suggested upgrades. I'd recommend that if you don't have anything crucial left to upgrade, then spend all your cells at the forge. This will improve the quality of the weapons and abilities you can find in the biomes. Following this, you're free to head to Stillt Village.
A note for "The Queen and the Sea" DLC owners:
Fully explore Stillt Village. Within one of the doorways, you'll discover the person that the fisherman pointed out, only to find him deceased. In this room, you need to defeat an elite enemy, which will reward you with a key and a new "Power," in this case, a pet named Leghugger. Make sure to collect the key and then exit the room.
While in Stillt Village, thoroughly explore the area, do the kills for the bonus if you want to, and leave towards the Forgotten Sepulcher.
Once you reach the Forgotten Sepulcher you'll earn:
- Afraid of the dark?
Reach the Forgotten Sepulcher for the first time!
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This biome stands out from the others due to a unique mechanic known as "The Darkness," which is self-explanatory. Remaining in the darkness for too long will gradually deplete your health. This effect intensifies the longer you stay in the dark. Fortunately, lamps are frequently placed to illuminate your surroundings, offering safety from the darkness and its effects. In this biome, you can obtain the Explorer's Rune, which proves quite useful. Possessing this rune and completing around 90% of a biome will permanently reveal the entire map along with all points of interest. To acquire the Explorer's Rune, you must defeat two elite Dark Trackers in this biome. They will grant you two crypt keys, which you can use to unlock the path to the next room, where the Explorer's Rune can be found. Apart from this, there isn't much else to do. Feel free to explore as much as you can, attempt the kill bonus if possible, and continue onward toward the Clock Room. Upon arriving at the Clock Room, defeat the boss and proceed to the next passage.
A note for "The Queen and the Sea" DLC owners: In this area, you can use the key that you've found on the corpse in Stillt village. If you use that key you'll have access to this DLCs biomes. We will come here later in our journey but it is good to have the door open for future walkthroughs.
In here spend all your cells. In my opinion, it is best to work towards getting the Specialist's showroom upgrade which has a prerequisite of 20 unlocked items from the collector. You may need to purchase some cheap weapons and items to progress towards this goal. Following this, the Restock Upgrade is also essential for subsequent playthroughs. Once you're ready, we will proceed towards the title update area, which can be challenging but unavoidable if you go for the 100% completion. Upon entering the Derelict Distillery, you'll unlock:
- Cheers!
Reach the Derelict Distillery for the first time!
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As I mentioned earlier, this area is tough, and you might find yourself creating checkpoints frequently in order to navigate and conquer this frustratingly challenging biome. Within this biome, you'll encounter dispensers that fire exploding barrels that bounce along the ground. Additionally, there are enemies capable of throwing these bouncing barrels towards you, inflicting significant damage. Apart from these challenges, two more unique achievements are tied to this title update. One requires completing the biome without ever using (or even picking up) the barrel launcher, and the other involves killing an Infected Worker with its own thrown barrel.
The first achievement is relatively simple: abstain from picking up the barrel launcher altogether. The launcher is located in one of the rooms. However, as you follow this guideline, bear in mind that to exit this dungeon, you'll need to utilize the Infected Worker at the end. Allow it to use a thrown barrel to blast open the exit door. The process isn't overly difficult; position yourself next to the door, wait for the Infected Worker to throw a barrel at you, and then evade the barrel to let it destroy the door.
Regarding the second achievement, you'll need to eliminate an Infected Worker using its own thrown barrel. You can deflect the barrel from a safe distance using any of your weapons. An electric whip is particularly effective as it automatically targets objects. If you successfully use the barrel to kill the enemy, you'll earn:
- Return to sender
You killed an Infected Worker with his own barrel!
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Once you're ready, proceed to the exit, leading to the Throne Room. This achievement is granted for completing the biome without ever picking up or using the barrel launcher:
- Born sapper
You completed the Derelict Distillery without using the Barrel Launcher!
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All that remains is to spend your cells for upgrades and leave for the Throne Room for the 2nd fight against the Hand of the King. Not much changes, the fight is 99% the same as before. After you beat him, he'll drop the 2nd boss stem cell which you will automatically collect earning the:
- Masterful extraction
Absorb your second Boss Stem Cell
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To conclude this run, follow the same steps as before, but this time, manually "eject" your "goo" from your body by pressing 
. Once you're controlling the goo, head to the fountain and exit through its tap to complete our second run, earning you another achievement:
- Up, Guards, and at them again!
Finish the game with a Boss Stem Cell active.
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With our 2nd run done let's head on for the 3rd BSC.
10. Obtaining the 3rd Boss Stem Cell8. Obtaining the 1st Boss Stem Cell
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