The cost of DNA sequencing has fallen at a faster rate than Moore’s Law, opening up big markets in the sequencing space. Genomics for cancer care alone is expected to reach $ 23 billion by 2025, but sample preparation costs for sequencing have stagnated, causing a significant bottleneck in space.
Conventional sample preparation, converting DNA from a saliva sample, for example, into something that can be fed into a sequencing machine, relies on a liquid handling robot. It is basically a mechanical arm equipped with pipette tips that move liquid samples to plastic plates and other instruments placed on the bridge. These systems involve multiple fluid transfers which lead to misuse of reagents and samples, which means less DNA sequencing. Additionally, they are separate data silo systems that lack integration and rely on expensive consumables.
Unlike traditional liquid management automation, the suite of solutions developed by Volta Labs, a spin-off of MIT Media Lab, offers end-to-end integration for a wide variety of workflows. It is a stylish alternative to expensive liquid handling machines and manual pipetting. “Our technology is a small-scale benchtop device that is inexpensive and has minimal use of consumables, enabling fast and flexible composition of new biological workflows,” said the co-founder and chief engineering officer of Volta Labs, Will Langford SM ’14, PhD ’19.
The Volta platform is based on digital microfluidics technology developed at MIT by Langford co-founder, Volta Labs CEO Udayan Umapathi SM ’17. The basic principle of innovation is called electrowetting. It allows its users to manipulate droplets around a printed circuit board to perform biological reactions, automating from the raw sample to the prepared library which can be run on a sequencing machine.
Umapathi came to Media Lab with what he describes as “a fascination with automating buildings from scratch”. Although trained as an engineer, Umapathi has applied his skills to a variety of fields. In 2015, he founded a startup that created web and physical tools to enable content creation for digital manufacturing. However, it was while working for a synthetic biology company, which was designing liquid handling systems for genome engineering solutions, that he identified increased automation as a problem for the domain.
Meanwhile, Langford spent his days at MIT at the Center for Bits and Atoms, a proudly interdisciplinary program that explores the frontier between computer science and the physical sciences. His research centered on the idea that engineering could learn from biology. In other words, all of life is assembled from 20 amino acids, so, Langford thought, why not try something similar with engineering?
In practice, this meant that he was building integrated robots from a small set of millimeter-scale parts. “At the end of the day, I was trying to make engineering look more like biology – biological reactions at finer granularity and with more numerical flexibility.
While Volta’s automation platform simplifies sample preparation by integrating complex workflows, it also cuts costs in space with new construction of consumables. Between the printed circuit board and the sampling board is a layer of consumables, which is removed and replaced after each scan. Conventional consumables are expensive, conduction encoded plastics or large microfluidic structures. Volta, however, uses a simple plastic wrap to reduce the cost of consumables, which opens the door to the widespread adoption of gene sequencing.
All of this points to a more efficient and inclusive model in the gene sequencing space. Thanks to Volta, there will soon be only large biotech companies capable of investing in automation. University labs, basic facilities, and small to medium-sized biotech companies won’t have to worry about whether they can afford an expensive mechanical robot. “What excites me is that we are providing early and mid to low stage biotech companies with powerful tools that will allow them to compete with bigger players, which is good for the industry as a whole. Umapathi says.
And the point is, traditional automation machines used in biotechnology have their own set of problems. They are error prone and you cannot scale them. Consider Illumina’s NovaSeq sequencer. It is capable of sequencing 48 entire human genomes in less than two days, or 20 billion unique reads, but there is currently no automation to power these machines on a large scale. “To run these machines day in and day out, the cost just doesn’t make sense, so we have to tackle the cost of sequencing and sample preparation,” Umapathi explains.
Volta’s system is built on solid-state electronics, and the Boston-based startup is looking to take advantage of the scalability of the semiconductor manufacturing industry and the PCB manufacturing industry. “The goal,” says Langford, “is to allow biologists to create an experiment and quickly modify it, iterate it and generate the data needed to see biology at scale.”
Beyond the bottleneck of sample preparation, the work of Umapathi and Langfordwork will ultimately impact a variety of applications in the synthetic biology industry and the biopharmaceutical industry. The diagnoses will be transformed, according to Umapathi. “We can help the biology industry by reducing the use of pipette tips by 20 to 50 times. In specific workflows, we can almost completely eliminate this bottleneck in the supply chain, ”he says.
To accomplish all of this, to truly innovate in a field as complex as biology, Umapathi and Langford insist that a multidisciplinary systems perspective is essential. This is what informs the Volta approach to genomic sequencing in particular, and biology as a whole. “Volta is a new kind of biotech company,” says Umapathi. “It’s inevitable that more engineers and systems thinkers and those who want to create tools to better design biology will join companies like ours or start their own. “
Transforming biology into an engineering principle is no small task, but according to Umapathi and Langford, it is a necessity.