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READ THIS ARTICLE ONLINE
`
`2022 Top 10 Innovations
`
`This year’s crop of winning products features many with a clinical focus and others that
`represent significant advances in sequencing, single-cell analysis, and more.
`
`The Scientist Staff
`Dec 12, 2022
`
`A
`
`s the acute phase of the COVID-19 pandemic recedes further
`
`into the global rearview mirror, life science research—and in
`
`ABOVE:
`© ISTOCK.COM, KRULUA
`
`particular, the tools that fuel it—continues to forge ahead. The past
`
`couple of iterations of  The Scientist’s annual Top 10 Innovations featured many products that
`
`directly addressed the (hopefully) once-in-a-generation disease outbreak, but also highlighted
`
`technological advances that pressed forward even in the face of that massive global disruption.
`
`This year’s winners reaffirm that the research enterprise has not only persevered but gained
`
`momentum as the world emerges from the worst that SARS-CoV-2 threw at us. These include
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`technology that can sequence a human genome for $100, highly sensitive imaging platforms for
`
`studying individual cells and subcellular compartments, and an assay system that facilitates protein
`
`discovery. There are also several tools with a clinical focus, such as personalized sequencing panels
`
`to detect residual cancer cells left after tumor removal, a software tracking system for overseeing
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`gene and cell therapies from bench to bedside, and a DNA processing tool that improves technicians’
`
`ability to analyze fetal DNA in a mother’s blood. 
`
`We are happy to announce the new products that our panel of independent judges has chosen as this
`
`year’s Top 10 Innovations.
`
`Read Interactive Article
`
`NeXT Personal™ Personalis
`
`         
`
`Small quantities of cancer cells can linger in the body after tumor
`
`removal, a phenomenon known as minimal or molecular residual
`
`disease (MRD) that, if left undetected, can lead to recurrence. Personalis’s NeXT Personal™ assay,
`
`unveiled in December 2021, uses a patient’s own tumors to detect, quantify, and monitor circulating
`
`tumor DNA in order to spot MRD and track responses to therapy.
`
`Using 1 mm3 of tumor tissue sampled from a patient, Personalis’s lab performs whole genome
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`Personalis EX2001.001
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`sequencing to identify up to
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`1,800 single-nucleotide
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`variants. These patient-
`
`specific mutations are used
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`to design a panel of primers
`
`targeting those regions for
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`sequencing in future blood
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`biopsies. The assay also
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`THE SCIENTIST STAFF
`
`includes primers for other known cancer-related genes,
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`says Dan Norton, associate director for product
`
`management at Personalis. “We can see if there are other
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`variants emerging that have a precision therapy associated
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`that may be more effective for that patient.” 
`
`Medical oncologist Jonathan Loree of BC Cancer and the
`
`University of British Columbia began partnering with
`
`Personalis in August to use NeXT Personal in a study of
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`patients who’d had tumors removed from their pancreases
`
`or colons, testing the technology’s ability to diagnose
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`disease recurrence “earlier when there is a window of opportunity for patients to still be cured,” he
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`says in an email to The Scientist. Loree says that if the assay could replace conventional diagnostic
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`CT scans and blood tests, “[t]hat has the potential to save money [and] improve outcomes.” 
`
`NeXT Personal is currently used in research only, with plans to expand to clinical trial settings next
`
`year, Norton says. Personalis declined to provide a cost for NeXT Personal, explaining that the price
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`varies depending on user needs.
`
`KAMDAR:  “NeXT Personal offers [the potential to] address a number of tumors that are not fully
`
`analyzed by other technologies to help identify and manage a patient’s disease.”
`
`         
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`CosMx™ Spatial Molecular Imager NanoString Technologies
`
`         
`
`The CosMx™ Spatial Molecular Imager (SMI) visualizes and
`
`quantifies RNA and protein levels at the single-cell and even
`
`subcellular levels. The platform, developed by NanoString Technologies, Inc., allows users to follow
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`a standard protocol to prepare and hybridize specific probes and antibodies to their samples, which
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`Personalis EX2001.002
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`PERSONALIS
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`can be frozen tissue slices or formalin-fixed, paraffin-embedded slices.
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`In the automated instrument, reporter sets hybridize and are imaged,
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`then the fluorescent dyes are cleaved with UV light and washed off
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`before the next reporter set hybridizes with the sample, allowing
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`researchers to image multiple targets in one sample.
`
`The CosMx SMI, priced at US$295,000, contains a high-resolution
`
`microscope and “allows researchers to visualize and quantify 1,000
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`RNA and 100 protein targets at a subcellular resolution across more than 1 million cells,” Vikram
`
`Devgan, senior director of Spatial Genomics Business at NanoString, says in an email to  The
`
`Scientist. He adds that users can also purchase the AtoMx™ Spatial Informatics Platform, a
`
`subscription-based software produced by NanoString, to visualize and analyze the data generated by
`
`the CosMx.
`
`“The CosMx is the only instrument that has provided us with the opportunity to simultaneously
`
`visualize thousands of genes, at subcellular resolution, and across all cells in a tissue,” says Miranda
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`Orr, an Alzheimer’s disease researcher at Wake Forest University School of Medicine in North
`
`Carolina who, after using another NanoString product, bought the CosMx SMI. “We are able to
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`develop maps of the brain at an unprecedented resolution.”
`
`QIAN:“This will transform the in situ spatial biology and molecular pathology fields.”
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`NANOSTRING TECHNOLOGIES
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`UG100™ Ultima Genomics
`
`         
`
`Ultima Genomics announced this May that it had developed
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`technology to sequence an entire human genome for US$100. Thus
`
`far, only early-access customers have had the chance to use the
`
`company’s new platform, called UG100™, but Ultima Genomics
`
`expects to release the product to the broader market in the first half of
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`2023. Compared to other sequencers, UG100 has several advantages,
`
`including higher speed, better efficiency, and less waste, says Josh
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`Lauer, the company’s chief commercial officer.
`
`Lauer attributes many benefits of the UG100 to a unique feature: a circular, open flow cell. Reagents
`
`are applied directly to  a spinning silicon wafer that distributes them more efficiently than reagents
`
`pumped through a traditional flow cell, Lauer explains. In addition, the revolving design increases
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`the speed of data collection and imaging, enabling Ultima’s sequencer to complete one run in about
`
`20 hours, which he says is about twice as fast as existing technologies. “Much like a CD player, this
`
`enables ultra-high-speed scanning of genetic material.”
`
`“I'm excited about the throughput of the platform, as well as the cost,” says Reuben Saunders, a
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`genetics graduate student at the Whitehead Institute who collaborated with Ultima Genomics to use
`
`its UG100 in recent research. “It’s heralding an exciting era where very large-scale experiments . . .
`
`will become accessible methods that can really drive advancements in our understanding of genetics
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`and cell biology.”
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`Lauer says the $100 per genome cost includes wafers and chemical reagents, but Ultima Genomics
`
`declined to release the price of the refrigerator-sized hardware that performs the sequencing.
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`RAO: “This is the first under $100 genome, and they have achieved it with an innovative use of
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`technology.”
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`         
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`ULTIMA GENOMICS
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`Proteograph™ Product Suite Seer
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`         
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`Proteomic studies have traditionally faced two key challenges, says
`
`Rebecca Rutherford, Director of Product Management at biotech
`
`company Seer: The need to tag proteins has restricted research to
`
`known proteins, and the large, diverse nature of the proteome has
`
`made investigating low-abundance proteins difficult. Seer’s
`
`Proteograph™ Product Suite, launched in January 2022, addresses
`
`both challenges, she says, using a nanoparticle-based assay that allows
`
`unbiased sampling of all peptides in a biofluid sample. “The
`
`innovation in the Proteograph Product Suite is really around our proprietary engineered nanoparticles
`
`that have unique surface functionalization that attract proteins across the entire dynamic range.” This
`
`allows researchers to track small molecular changes associated with disease and reveals distinct
`
`protein variants produced by post-transcriptional modifications, Rutherford says, enabling the
`
`identification of novel and biologically relevant proteoforms.
`
`“From a [discovery] proteomics perspective, the complex liquid biopsies like blood, serum, and
`
`plasma that we work with have just been inaccessible,” says Mark Flory of the Cancer Early
`
`Detection Advanced Research Center (CEDAR) at Oregon Health & Science University Knight
`
`Cancer Institute who collaborated with Seer to test the new platform before becoming the first client
`
`to purchase it. Proteograph enables “deep sampling in those very complex liquid biopsy types.” His
`
`research team has been applying the platform to a large cohort study of prostate cancer to identify
`
`new biomarkers. The product is also being applied to research on lung cancer and Alzheimer’s
`
`disease, according to Rutherford.
`
`Seer declined to provide a price for the Proteograph™ Product Suite.
`
`KAMDAR: “Provides access to the proteome in an unbiased way and does for proteomics what
`
`next-generation sequencing has provided in genomics.”
`
`         
`
`LIVE T Cell Assay Nanolive
`
`         
`
`Over the past decade, Nanolive has developed imaging platforms
`
`based on technologies that reconstruct three-dimensional holo-grams
`
`of label-free samples. In September 2021, they launched their first application-specific digital assay,
`
`LIVE T Cell Assay, which examines how T cells locate, bind, stress, and kill their targets, such as
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`SEER © 2022
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`infected, foreign, or cancerous cells. The assay measures phenotypic
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`and morphological parameters of both the T cells and the target cells,
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`but “what’s really novel about the product is the metrics that we can
`
`extract from the interaction between the two,” says Emma Gibbin-
`
`Lameira, scientific communications manager at Nanolive. Such
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`information can be very powerful in testing the efficacy of a drug, she
`
`adds. For instance, you can assess whether a specific antibody brings T
`
`cells closer to the desired target and whether it increases the cells’ killing rate.
`
`Valery Moine, a unit head in the Pharmacology group at Switzerland-based Light Chain Bioscience
`
`who collaborates with Nanolive, says he started using LIVE T Cell Assay a year ago to create
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`“marketing videos to highlight and promote the mode of action of bispecific antibodies” developed
`
`by his company. More recently, he says he has been using the platform to further characterize these
`
`antibodies. The metrics it provides, he adds, are valuable for ranking the best candidates.  
`
`Nanolive declined to share the price of the assay, but Lisa Pollaro, the chief marketing officer at the
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`company, writes in an email that “it comes with an annual license with a price in the same range of
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`chemical assay kits available in the market.”
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`RAO:  “A non-end point assay for the rapidly developing field is a huge advance in enabling
`
`therapy.”
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`         
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`NANOLIVE
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`MARS® Bar Applied Cells, Inc.
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`         
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`One of the most efficient methods to select cells is immunomagnetic
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`separation, where the isolation is based on the presence of magnetic
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`beads attached to specific cell surface antigens. There are several
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`products on the market that apply this method, but a new system
`
`presented by Applied Cells, Inc., called MARS® Bar, has various
`
`advantages, says Liping Yu, vice president of applications at the
`
`company. For instance, MARS Bar works as a closed system with
`
`sterile fluidic kits, which makes it “much easier to manage,” says Yu,
`
`because its use is no longer restricted to a clean room or biosafety cabinet. Additionally, the device
`
`contains three modules, allowing it to process three samples in parallel.
`
`Sergei Rudchenko, an assistant professor at Columbia University who has an ongoing scientific
`
`collaboration with Applied Cells, has been using a version of the product, MARS Bar Flex—quite
`
`similar but with open fluidics—since February for a protocol that aims to remove naive T cells from
`
`peripheral blood mononuclear cells during cell transfusion. According to Rudchenko, who says he is
`
`interested in developing the protocol into a clinical application to prevent graft-versus-host disease,
`
`MARS Bar Flex achieves about eight times higher recovery of blood cells after depletion of
`
`unwanted cells than other published protocols, in addition to “quite competitive purity.” 
`
`According to Yu, MARS Bar is customizable but will cost around US$150,000 for the standard
`
`three-module configuration once it is available on the market. The company started demoing this
`
`new model at customer sites in November, she adds.
`
`RAO:  “Very innovative use of magnetic separation technology without fixed magnets allowing a
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`high throughput.”
`
`         
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`MARS® BAR, APPLIED CELLS INC. 2022
`
`Single Cellome™ System SS2000 Yokogawa Electric Corporation
`
`         
`
`The Single Cellome™ System SS2000 by Yokogawa Electric
`
`Corporation is an automated subcellular sampling system, which
`
`contains both a dual spinning-disk confocal microscope to visualize
`
`tissue and a sampling setup to collect whole cells or intracellular
`
`components from a single cell.
`
`The system, launched in February 2022 in Japan, the US, and China,
`
`can be fully automated, giving users the ability to define which cells
`
`should be sampled based on their cytoplasm area, nucleus size, or other morphological features.
`
`Cells that fit a particular profile are aspirated and deposited in a 96-well plate for further analysis.
`
`The system can also directly sample intracellular components such as organelles or parts of the
`
`cytoplasm and combine these insights with whole-cell sampling. The SS2000’s “high-resolution 3D
`
`image allows researchers to control the location of [cell and subcellular] sampling in a highly precise
`
`way and retains the spatial context,” says Takanobu Kiuchi, head of global marketing at Yokogawa.
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`“We can sample multiple times from the same cell, you collect a small intracellular sample for
`
`metabolomics, and then collect the rest of the cell for single-cell transcriptomics,” says Carla
`
`Newman, associate director of Cellular Imaging and Dynamics at GSK, who received an SS2000
`
`from Yokogawa as part of a research collaboration agreement for beta testing, Especially for rare
`
`phenotypes, she notes, the ability to target sampling to specific features is highly useful, as well as
`
`being able to sample small numbers of patient cells. “It allows for  the granularity of the single-cell
`
`level to pick up rare events.” Newman adds that the SS2000 is faster and easier than traditional
`
`micromanipulators, improving the sampling speed by at least 10 times.
`
`Depending on the technical configuration and required support, the instrument list price ranges from
`
`€650,000 (US$651,800) to €725,000 (US$727,088).
`
`QIAN:  “This is a highly innovative system coupling high resolution cellular imaging with
`
`subcellular sampling technology.”
`
`         
`
`YOKOGAWA ELECTRIC CORPORATION
`
`LightBench® Detect Yourgene Health
`
`         
`
`The LightBench Detect® is a DNA processing tool that is useful for
`noninvasive prenatal testing (NIPT), which involves fetal DNA
`
`collected from the mother’s blood. To help find the tiny strands of fetal DNA among the clusters of
`
`maternal DNA, the LightBench Detect separates the fragments by length, explains Yourgene Health
`
`product manager Becky Underwood.
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`The product employs Yourgene’s imaging system, Ranger
`
`Technology, to image the gel and make real-time adjustments to the
`
`voltage to optimize strand separation, Underwood says, adding that the
`
`LightBench Detect is the only instrument on the market that can use
`
`plastic EDTA blood collection tubes, which are cheaper, less
`
`susceptible to breakages, and more efficient than the industry standard
`
`glass ones. These features yield 50 to 75 percent more fetal DNA per
`
`sample, according to Yourgene’s product page.
`
`The instrument, which costs US$50,000, launched in early June and is still in its testing stages with
`
`company scientists and a few outside researchers, Yourgene tells The Scientist. Bhavika Patel,
`
`director of the Yourgene genomics services lab that is using the product, says its usage of EDTA
`
`tubes has significantly cut down the lab’s costs and failure rates, potentially putting less strain on
`
`patients and getting quicker results. “It’s quite a nice, neat instrument,” Patel says. 
`
`In addition to its use for NIPT, Underwood says the LightBench Detect has a wider range of
`
`applications, including scanning blood samples for tumor DNA or infectious pathogens. “We want to
`
`positively influence clinical pathways and improve patient outcomes,” Underwood tells The
`
`Scientist.
`
`VAN VLIET:  “This can be a game changer for widely used diagnostics globally, especially given
`
`price point and ease of sample preparation.”
`
`         
`
`Molecular Cartography™ Resolve Biosciences
`
`         
`
`Resolve Biosciences’s Molecular Cartography™ workflow is a single-
`
`molecule fluorescence in situ hybridization technology that offers a
`
`three-dimensional view of gene expression within cells without
`
`damaging the tissue section or cell culture sample. The company
`
`launched the platform as a mail-in service last year, and that service
`
`won a spot in the 2021 Top 10 Innovations list. Resolve Biosciences
`
`began installing hardware and software for the fully automated
`
`Molecular Cartography workflow in customer laboratories in January
`
`2022, for a cost of US$400,000.
`
`“We’re able to bring the assay into the actual disease state and map interactions at the single
`
`Personalis EX2001.011
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`

`YOURGENE HEALTH
`
`molecule level within tissues,” says Jason T. Gammack, cofounder and CEO of the firm. The
`
`platform produces high-resolution images of subcellular gene expression, which, in addition to
`
`providing unique insights into the transcriptional landscape of the cell, are “quite breathtaking,”
`
`Gammack says. “You now see the beautiful symmetry of biology.” 
`
`“It is a ready-to-go system that needs very little optimization,” says Jan-Philipp Mallm, head of
`
`the Single-Cell Open Lab at the German Cancer Research Center (Deutsches
`
`Krebsforschungszentrum, DKFZ). A major advantage of Molecular Cartography is its fully
`
`customizable panel of probes, says Mallm, who used the mail-in service before purchasing the full
`
`workflow for his laboratory this year. “I think the versatility is a big asset of the system.” Mallm and
`
`his colleagues are applying the technology to study the cancer microenvironment, where “a tumor
`
`can be regarded as a whole complex tissue and thus needs single-cell spatial resolution in order to
`
`understand its function and capabilities.”
`
`KAMDAR: “This view of subcellular gene expression activity can facilitate new insights into the
`
`Personalis EX2001.012
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`interactions and complexity of critical biological mechanisms.”
`
`require, Lakelin notes.          
`
`affairs and product development. OCELLOS 3.0 not only bolsters the safety and quality of such
`
`treatments, but it manages the chain of identity and chain of custody data that regulatory agencies
`
`Personalis EX2001.013
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`RESOLVE BIOSCIENCES
`
`OCELLOS 3.0 TrakCel
`
`         
`
`Cell and gene therapy have started to revolutionize medicine, but
`
`they’ve also presented new challenges in tracking the materials
`
`involved, including patients’ own cells. To address these challenges,
`
`TrakCel introduced a cloud-based software called OCELLOS in
`
`February 2021 and released a new iteration, OCELLOS 3.0, this July.
`
`“It’s a really simple computer interface that’s easy to access
`
`throughout the whole supply chain,” says Matthew Lakelin, a
`
`cofounder of TrakCel and the company’s vice president of scientific
`
`

`

`Edward Armstrong, senior director of quality assurance at Mustang Bio, has been partnering with
`
`TrakCel since 2018, using their technology to track Mustang’s autologous CAR T cell products and
`
`cell and gene therapies during clinical trials. “Chain of custody and chain of identity are critical to
`
`our process and are looked at very heavily by the Food and Drug Administration,” says Armstrong,
`
`who is currently switching to OCELLOS 3.0. When Mustang Bio was looking to enroll its first
`
`patient, Armstrong considered tracking the products on paper, but quickly realized that “to do on
`
`paper what TrakCel does electronically would drive mortal men insane.”
`
`TrakCel’s OCELLOS 3.0 starts at $300,000, but the price may increase based on the amount of
`
`involvement and customization desired.
`
`VAN VLIET:  “This product can help focus, simplify, and reduce errors in the complex supply chain
`
`and task logistics of cell/gene therapy (CGT) development and production.”
`
`         
`
`TRAKCEL
`
`THE JUDGES
`
`
`
`Personalis EX2001.014
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`

`

`Kim Kamdar
`
`Managing partner at Medical Excellence Capital, a healthcare-
`
`focused venture fund creating and investing in biopharma and
`
`diagnostic companies. She began her career as a scientist and
`
`pursued drug-discovery research at Novartis/Syngenta for nine
`
`years.
`
`
`
`Wei-jun Qian
`
`Bioanalytical chemist at Pacific Northwest National
`
`Laboratory. His research centers primarily on the development
`
`and applications of mass spectrometry–based approaches to
`
`better quantify the dynamic changes in protein abundances and
`
`protein post-translational modifications in biological and
`
`clinical applications.  
`
`Mahendra Rao
`
`CEO at Implant Therapeutics. Rao has published more than
`
`200 papers on stem cell research and is the cofounder of the
`
`neural stem cell company Q Therapeutics, based in Salt Lake
`
`City, Utah. He has served on advisory panels for the US Food
`
`and Drug Administration (FDA), as well as for the
`
`governments of the US, Singapore, and India on policies
`
`pertaining to human embryonic stem cells. He continues to
`
`
`
`work with the FDA and other regulatory authorities on issues related to pluripotent stem cells.
`
`
`
`Krystyn Van Vliet
`
`Michael (1949) and Sonja Koerner Professor in the departments of materials science and engineering
`
`and biological engineering at MIT. She also leads the Singapore-MIT Alliance for Research and
`
`Personalis EX2001.015
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`

`Technology's Critical Analytics for Manufacturing
`
`Personalized-Medicine (CAMP) research team.
`
`https://www.the-scientist.com
`
`© 1986–2023 THE SCIENTIST. ALL RIGHTS RESERVED.
`
`Personalis EX2001.016
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`

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