Method and apparatus for simultaneous targeted sequencing of DNA, RNA and protein

A multiomic detection method for detecting DNA, RNA, and protein from a cell, comprising:

• combining the cell with antibody-oligonucleotide tags, wherein antibodies of the antibody-oligonucleotide tags exhibit specificity for proteins of the cell;
• encapsulating the cell and antibody-oligonucleotide tags in a drop comprising a reaction mixture comprising a protease;
• performing a protease digest on the encapsulated cell drop with the protease to produce a cell lysate, wherein the cell lysate comprises DNA, RNA, and oligonucleotide tags derived from the antibody-oligonucleotide tags;
• providing a reverse transcriptase and generating cDNA by performing a reverse transcription reaction on the RNA;
• combining cell lysate comprising DNA, cDNA, and oligonucleotide tags with barcoding reagents and barcoding beads;
• performing a nucleic acid amplification reaction to attach the cell barcodes to amplicons derived from the DNA, cDNA, and oligonucleotide tags, wherein amplicons from the drop contain a same cell barcode;
• and
• detecting DNA, RNA, and protein of the cell by sequencing the cell barcode incorporated into the amplicons.