Our Gemara on amud beis discusses the dictum of Shmuel, which states that in order to release the obligation of Terumah from produce (which is forbidden to eat prior to taking off the Terumah, known as Tevel), even setting aside one grain of wheat for Terumah is sufficient. (Although the Rabbis required 1/60-1/40 as an appropriate gift to the Cohen.) The idea that a small grain of sanctification can accomplish so much becomes a launching point for mystical commentaries to encourage certain actions and thoughts in spiritual development.
The Shalah (Shenei Luchos HaBeris, Torah Shebiksav, Toldos, Torah Ohr 1) notes important numerological patterns in the process of the various tithings. The concept that one must make 100 blessings a day (Menachos 43b) represents the 100 channels through which God's blessings flow into the world, also symbolized by the "100 sockets" that support the walls of the Mishkan (Tabernacle) (Shemos 38:27), a simulacrum of the world itself, and the 100 gates of blessings that Yitschok received from his produce (Bereishis 26:12). Maaser, one tenth, is represented by the Hebrew letter Yud, whose numerical value is 10. This Hebrew letter itself is nested, as the formation of the proper Hebrew script Yud in the Torah is comprised of a Yud but also has a small Yud crowned on top of it (see Mishna Berura, Mishnas Soferim 36:45). Furthermore, the "full" spelling of the letter Yud is Yud-Vav-Dalet, which means that within the Yud is a third nested Yud, the gematria of the Vav+Dalet.
Following this numeric structure, we find three tithes, represented by the Yud itself, which is the tenth, then the numeric Yud within the Yud, which is the Vav-Dalet, and finally the tip of the Yud, which is a small Yud. This corresponds to three different sanctified gifts: the Masser (tenth of produce given to the Levite), the Terumas Maaser, which is the Terumah that the Levites give to the Cohanim from their portion and is also a tenth (Bamidbar 18:26), and finally the actual Terumah for the Cohen from the Israelite portion, which is, in principle, even one grain. This one grain, the tiniest of units, symbolically represents the tip of the Yud, the smallest of letter strokes. Also notably, the Terumah for the Cohen, known as Terumah Gedolah, is taken by estimated intention and not actual measurement (unlike the other tithes, as mentioned in Menachos 54b and see Rambam and Kesef Mishne, Terumos 3:10, following Yerushalmi). The first two tithes are God’s Sefirotic channels of blessings, first the one of the Ten Sefiros, and then God’s holiness represented in the tenth Sefira itself. However, even beyond that is an unknowable and unquantifiable essence of God, which is represented in the tip of the Yud, the tiniest finest element, and the Teruma Gedolah, which is a tiny grain and made by estimate and intention. The highest level of relation and connection to God cannot be measured or quantified and must be felt through.
Other commentaries develop this idea further (Sefas Emes, Shemos, Terumah 6.2 and Tzafnas Pa'neach on Torah, Haftaros, Beha'alosecha). The tiniest grain represents the root of the Jewish soul, which, once aroused to connect to Hashem, can sanctify the entire person. As the famous saying goes in God’s name (Shir Hashirim Rabbah 5:2), “[When repenting], make an opening for me as small as the point of a needle, and I will open for you gateways that wagons and trucks can pass through.”
Translations Courtesy of Sefaria, except when, sometimes, I disagree with the translation 
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