Elizabeth Holmes will begin an 11-year jail term this month after losing a bid to stay out of prison while she appeals against her conviction over the Theranos scandal.
The 39-year-old was sentenced in November for what prosecutors had branded as "among the most substantial white collar offences Silicon Valley or any other district has seen".
She launched Theranos with the promise of delivering revolutionary blood-testing technology that could check for dozens of diseases at once - and raised nearly $1bn (£840m) from a host of high-profile investors.
It helped her become America's youngest-ever self-made female billionaire by 2014, but the tech was exposed as bogus and the company - once valued at $9bn (£7.3bn) - quickly came crashing down.
She was found guilty by a Californian jury of three counts of investor fraud and one count of conspiracy.
Since her sentencing, Holmes's lawyers have tried to persuade an appeals court that alleged misconduct during her four-month trial led to an unjust verdict.
But in an 11-page ruling, US district judge Edward Davila said there was not enough compelling evidence for the Stanford University dropout to remain free while the appeal is heard.
The judge said while Holmes was "not likely to flee" or endanger the public if kept out of prison, her conviction was unlikely to be overturned.
It means she must surrender to authorities on 27 April.
Holmes will be separated from her two children, one she had leading up to the trial and one after her sentencing.
She had both with current partner William Evans, who she met after breaking up with Theranos co-conspirator Ramesh "Sunny" Balwani.
Balwani, who was the company's president, will begin a nearly 13-year prison sentence on 20 April.
While he will report to a Southern California jail, Mr Davila has recommended Holmes serves her term in Texas.
Holmes's term will begin almost exactly 20 years after she dropped out of Stanford to found Theranos, inspired by the successes of Silicon Valley heavyweights like Apple boss Steve Jobs.
Her astonishing rise and fall from history-making billionaire to the brink of jail has inspired documentaries, podcasts, and an award-winning TV drama - The Dropout - starring Amanda Seyfried as Holmes.