Prior to Rothberg's birth, his parents founded Laticrete International, Inc. a family-owned manufacturer of products for the installation of tile and stone.

[8] The idea for 454 Life Sciences came when Noah, his second child, was born in 1999, and had to be sent to the neonatal intensive care unit because of breathing troubles.

[3] Noah turned out to be fine, but Rothberg was frustrated that doctors did not have a rapid test to ensure his son did not have an inherited disease.

The companies focus on using inflection points in medicine, such as deep learning, next-generation sequencing, and the silicon supply chain, to address global healthcare challenges.

4Catalyzer companies include Butterfly Network, Quantum-Si, Hyperfine, Tesseract Health, Liminal Sciences, Detect, AI Therapeutics, and Protein Evolution, Inc.[16] In 2011, Rothberg founded Butterfly Network after seeing a talk by MIT physicist Max Tegmark, who was becoming fascinated by artificial intelligence.

[17] Rothberg brought in one of Tegmark's smartest students, Nevada Sanchez, a co-founder of the company who was named among Forbes 30 Under 30 in 2015.

[17] Butterfly Network sells a hand-held ultrasound imaging device that connects to an iPhone, called the iQ.

[18] In September, 2018, Butterfly Network raised $250 million from investors Fidelity, the Gates Foundation, and Fosun Pharma at an estimated $1.25 billion valuation.

Rothberg founded Quantum-Si in 2013 with the mission of transforming single molecule analysis and democratizing its use by providing researchers and clinicians access to the proteome, the set of proteins expressed within a cell.

[25] The Hyperfine Swoop is commercially available and saving lives on multiple continents around the world, including limited resource settings in Africa and Asia where access to MRI was never before possible.

The company aims to support the screening, diagnosis, and monitoring of disease, both affordably and non-invasively using "the power of data in the human eye".

Inspired by both the utility and the limitations of EEG (electroencephalogram), Liminal has invented AEG, a new modality that combines blood flow measurement with the existing technology that monitors the electrical activity of the brain.

[citation needed] Protein Evolution was founded in October of 2021 with the mission to help the chemicals and materials industries transition to a lower-carbon, more circular economy.

[33] Rothberg had his own version of Stonehenge, which he calls the Circle of Life, built near his home in Guilford, CT, using 700 tons of granite imported from Norway.