Top 10 Innovations 2016

Top 10 Innovations 2016

This year’s list of winners celebrates both large leaps and small (but important) steps in life science technology.

By The Scientist Staff | December 1, 2016

(http://www.the-scientist.com/?articles.view/articleNo/47537/title/Top-10-Innovations-2016/)

Oftentimes innovation is incremental. After all, even big, brash new ideas have nuts and bolts that can be endlessly tweaked to improve performance, efficiency, and utility. This year’s Top 10 Innovations winners do include bold, new platforms that look primed to rev up discovery in basic biology, drug development, and clinical labs. But the list also fea­tures products that speak to the important, but often underappreciated, tinkering that drives life science innovation.

Just as geneticists might revel in the release of a new platform capable of generating long-read sequences with single-molecule resolution, synthetic biologists eagerly await the development of improved CRISPR-Cas9 guide RNAs and nucleases to facilitate ever more efficient and precise genome editing. Like biology itself, life science technologies are often more than the sum of their parts.

Also worth mentioning are the more clinically relevant innovations that made this year’s Top 10 list. Synthetic human kidney tissue that brings properties of the organs to the petri dish and specially designed panels that quantify a host of biomarkers in various samples promise not only to enhance work in the lab, but to change lives in the clinic. Advances like these remind us that innovation and the pace at which it occurs serve more than manufacturers, developers, and academics—they can serve humanity.

From a machine that allows for single-cell Western blotting to a microfluidic device that streamlines mass spectrometry, this year’s Top 10 Innovations are a celebration of transformative life-science advances, large and small.

ProteinSimple >> Milo

Single-cell Western blotting is now available for purchase. Developed by Amy Herr’s lab at the University of California, Berkeley, Milo is a benchtop instrument that allows researchers to search for specific proteins in about 1,000 single cells at once. Users simply pipette a cell suspension on top of a 1-by-3-inch glass microscope slide covered in a 30-micron thick gel layer dotted with 6,400 microwells. As the cells settle into the gel, some wells will remain empty, but about 1,000 will collect individual cells for analysis.

Researchers then add reagents to chemically lyse the cells and denature the proteins. Next, they apply a charge to pull the proteins into the space between the wells and use UV light to activate chemicals in the gel that lock the protein bands into place.

“People who are doing conventional Westerns can’t see heterogeneity, because they’re looking at a bulk level,” says Kelly Gardner, a former graduate student in the Herr lab and current director of marketing at ProteinSimple. “Milo gives you access [to] identify subpopulations.” A description of the technology was first published in June 2014, and strong interest from the scientific community led Herr, Gardner, and their colleague Josh Molho to launch Zephyrus Biosciences, which was acquired by ProteinSimple’s parent company Bio-Techne in March. The company declined to give the exact price of a Milo unit, but stated that Milo’s cost is comparable to a benchtop flow cytometer, and that interested researchers can request a quote on the website. The company was also unable to provide user comment due to the newness of the product. Unger: A novel use of a custom chip that eliminates the transfer step and allows efficient large-scale tests of thousands of single cells. As price keeps coming down, this should allow the detailed efficient testing of many problematic (e.g., poor flow) proteins, and give info about individual cellular responses, which is an important area of inquiry today. Fishman: This is an example of the potential for scalability of a known technology at lower cost and using less space. This also saves researchers’ time by testing protein-expression heterogeneity in their cells, simultaneously.

Organovo >> ExVive Human Kidney Tissue

A crucial stage of drug development is testing whether a candidate compound damages the kidneys, but existing cell cultures and animal models can only approximate the human kidney. ExVive Human Kidney Tissue from Organovo is a replica of the kidney proximal tube created using 3-D bioprinting. It offers drug developers a reliable means of testing for renal toxicity.

Currently, few preclinical tests can determine whether a potential drug is toxic in humans, making investing in clinical testing risky for developers. Identifying renal toxicity early on reduces that risk. More importantly, “you’re really talking about doing no harm to the patients that are going to be in the clinical trial,” says Organovo Chief Scientific Officer Sharon Presnell.

Bioprinting operates on a similar principle to 3-D plastic printing, explains Presnell, but “instead of putting beads of polymer into a printer, we’re putting little aggregates of cells.” Organovo, which won a spot in 2014’s Top 10 Innovations for its ExVive Liver Tissue, produces tissue samples on a contract basis, and pricing can vary widely depending on the number and type of samples a client requires.

The replica kidney tissue could be applied outside of toxicology too, as a platform for experiments on kidney tissue that would not be otherwise feasible, Presnell says.

“It seems to have integrity like a native kidney tissue,” says Caroline Lee, a metabolism and pharmacokinetics researcher at Ardea Biosciences who profiled transport protein expression in the artificial tissue. Lee found that directional transport proteins were oriented correctly along the membrane. “You can see drugs going in the right direction,” she says. “It’s pretty remarkable.”

Unger: Based on quite a novel and bold approach to copying the detailed morphology and function of kidney tissues, this innovation offers major advantages over conventional cell culture methods, which have limited predictive capacity at the tissue level.

Fishman: This technology can be used instead of preclinical animal trials, reducing our reliance on laboratory animals to test new compounds. It also has the potential to transform drug development by better mimicking human kidney biology to test for the renal toxicity of new drugs.

Pacific Biosciences >> The Sequel System

At less than a third the size and weight—and half the cost—of Pacific Biosciences’s original long-read sequencer, the Sequel System is the company’s latest offering in single molecule, real-time (SMRT) sequencing.

Sequel, which debuted last fall, generates the same long reads and single-molecule resolution accomplished by the company’s older SMRT sequencer, called the PacBio RS II. Compared with the RS II, Sequel “is a higher throughput version of SMRT sequencing, which allows the faster generation of more data to tackle larger genomes and biology requiring higher molecular depth as well as metagenomic samples in the same relative time frame,” says Robert Sebra of the Icahn School of Medicine at Mount Sinai in New York City who has used the system since December 2015.

Sebra, who worked at PacBio from 2007 to 2012, has used SMRT technology for various applications over the past six years, including de novo human genome sequencing. “It’s very flexible for both R&D and production sequencing,” he says. “There’s essentially no systematic error, enabling higher quality value sequence data in tandem with longer reads to help discover previously unknown genomic features.”

Sequel is also particularly useful for metagenomics and infectious disease research. It was recently used to produce a reference genome sequence of a Korean individual, says Jonas Korlach, chief scientific officer at PacBio and coinventor of SMRT sequencing (Nature, 538:243-47, 2016). In October, leaders of the Genome 10K (G10K) and Bird 10,000 Genomes (B10K) initiatives announced their choice of SMRT sequencing as a principal technology.

With a list price of US$350,000, a PacBio sequencer is within reach for more labs. “Now, SMRT sequencing is for everyone,” says Korlach.

Fishman: The Sequel System is an improvement on Pacific Biosciences’s earlier systems in that it provides higher throughput and more scalability at a lower cost. StrÖmvik: Though not affordable for small labs, high-throughput, long-read sequencing is essential for any group working on large and complex genomes, metagenomics, and metatranscriptomes.

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