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Spot On Sciences Looks to Broaden Use of Dried Blood Spots in Clinical Testing, Molecular Analyses

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Spot On Sciences, an approximately four-year-old startup based in Austin, Texas, is looking to move dried blood spot technology from centralized laboratories and specialized applications like neonatal screening to widespread clinical and molecular diagnostic applications.

To that end, with $1 million worth of support from the Defense Advanced Research Projects Agency, the company is commercializing a novel DBS technology that would allow anyone to take a blood sample in any location and ship or store the samples at room temperature for downstream analysis or point-of-care diagnostic testing.

In addition, scientists from the company in recent months have presented scientific posters demonstrating that circulating microRNA biomarkers can be measured with real-time PCR from DBS and patient finger pricks just as effectively as from traditional venous blood samples.

DBS sampling has been used to screen newborn babies for congenital metabolic diseases for more than 40 years, Spot On explains on its website. Typically, a spot of blood from a heel stick of the infant is placed on filter paper and allowed to air dry. An approximately 3-mm circular punch is then removed, eluted with solvent, and analyzed for biomarkers.

Dozens of analytes can be measured from a quarter-sized spot of blood and, as reported earlier this year in ProteoMonitor, the proteomics field in particular has seen the potential benefits, with researchers in recent years marrying DBS technology and mass spectrometry analysis for pharmacokinetic analyses and, potentially, widespread protein-based biomarker testing.

The idea behind founding Spot On was to "bring dried blood spots, a great technology that works well for newborn screening, to the rest of us," Jeanette Hill, founder and CEO of Spot On, told PCR Insider in a recent interview.

"My background is in pharmaceutical research, and we had just started using [DBS] technology for clinical research and pre-clinical research — it just works so well," Hill added. "The way we do blood sampling now, the venipuncture, is just so outdated. You have to travel to the lab, and it's really a big burden for people who are elderly or sick, or live in a rural or remote area."

DBS as a sample-collection medium does have its drawbacks, however, such as the fact that the blood needs to air-dry for several hours prior to shipping or storage, potentially exposing the sample to contaminants. This is especially problematic in resource-poor areas of the world, where the technology otherwise could be a boon.

Furthermore, it can be difficult to properly apply the blood spot to current filter paper-based collection devices, limiting patients' ability to collect their own blood samples. Meantime, once the DBS sample reaches a central laboratory, it is crucial that technicians punch a spot from a truly representative area of the dried bloods in order to avoid variable analytical results.

Spot On seeks to address these issues and more with its technologies, HemaForm and HemaSpot. HemaForm is a fan-shaped form of absorbent material designed to improve DBS collection — a sample is applied to the center of the form then wicks out evenly on to the eight wedge-shaped "blades" of the fan.

These individual blades promote more uniform sample coverage and faster drying, and can be more easily individually removed for subsequent downstream analysis.

"You can take one blade — or, in some cases you might need two, depending on how much sample you need — and put it into either a 96-well plate or an Eppendorf tube," Jeanette Hill, founder and CEO of Spot On, told PCR Insider in a recent interview. "Then you just extract with solvent … and elute, then basically can treat it like a regular blood sample."

HemaSpot, meantime, is the company's blood collection device that contains the HemaForm paper and a desiccant covered with an application surface that contains a small opening to allow entry for blood. A patient can use the device to stick his own finger, collecting two drops of blood which are rapidly dried inside the cartridge. The sample is immediately ready for shipping or storage while the moisture-tight cartridge and tamper-resistant latch assures the sample remains uncompromised, according to Spot On's website. The device is approximately the size of a credit card and about 1 cm tall when closed.

"The idea is to make it easy enough for someone to pick it up at the store, your doctor's office, and take it home, or we mail it to you," Hill said. "Open it up, stick your finger, put your drops of blood on, close it up, and it's ready to put in the mail or put in your pocket to bring to a lab somewhere."

Last year, Spot On received a two-year, $1 million Small Business Innovation Research grant from DARPA to further develop the device, potentially for use in point-of-care diagnostics. As part of that work, Spot On has been working to validate that its technology is compatible with a variety of downstream analysis methods. In house, Spot On focuses primarily on mass spec assays. But the company also works with a small Texas-based contract research organization called ARQ Genetics to explore use of the spots with other molecular analysis modalities.

At the Association for Molecular Pathology meeting held last month in Phoenix, Ariz., Spot On and ARQ Genetics presented a poster assessing the ability to analyze circulating miRNA biomarkers from dried blood spots using real-time PCR.

The group chose several representative miRNA molecules that are detected at various levels in human blood, and analyzed those markers in both wet blood samples from venipuncture and dried capillary blood collected by finger stick and dried using HemaSpot. For PCR analysis, the researchers used a TaqMan microRNA reverse transcription kit and 7900HT Fast real-time PCR system from Life Technologies.

They were able to measure equivalent miRNA levels in wet versus dried blood, and in venous versus capillary samples. They also noted that heparin, an anticoagulant used for venous blood, reduces miRNA detection 10-fold, likely due to heparin inhibition of PCR, further supporting the idea that DBS samples could be a superior sample collection modality.

"We are very interested in [circulating] microRNA as biomarkers, and we couldn't find anyone who had published or done anything on DBS," Hill said. "We did this study to basically show that, compared to wet whole blood, you basically get the same results. Also, the question often comes up whether you get the same amount [or biomarkers] in a capillary finger stick versus venous, and in this case we did get exactly the same amount, so that was not an issue. It works very well, and it is so much easier to get a finger stick sample than a venipuncture."

The potential for clinical testing is clear, but Spot On believes that its technology can also better enable certain types of biomedical research. For instance, the company is currently collaborating with the laboratory of Ramon Hermida at the University of Vigo in Spain to use HemaSpot to enable subjects to collect blood samples throughout the day in order to investigate how circadian rhythms affect the efficacy of blood pressure medications and, more broadly, how miRNA levels correlate with circadian rhythms.

"We're looking at different biomarkers, and microRNAs are key," Hill said. "We had donors take samples at eight time points throughout a 24-hour period — so right when they get out of bed, within 10 minutes, and this is something that our device allows. It's really never been done before, to take a sample right when you get out of bed, and in the middle of the day, and we've even had some people do this while they're at the beach or mall … or in the middle of the night."

Spot On's primary focus in the short term, however, is to get HemaSpot in the hands of clinical researchers in resource-poor areas of the world. But Hill noted that the potential applications are broad — perhaps too broad.

"One of the problems that we have is there are many, many markets that this could work for," she said. "We have explored them and talked to a lot of customers. Where we're really getting traction, initially, are groups that have already started or considered using DBS. They are the most motivated. Things like HIV [and] infectious disease testing, especially for developing countries. That seems to be where there is a huge need for something like this."

Another potential market is wellness testing, "where you can order a test on the web and they'll send you a kit." Spot On is working with another undisclosed company in this market to launch a website in January that will focus on this market, Hill said, although the initial focus will not be on molecular testing but on analytes such as HbA1c for diabetes testing or prostate-specific antigen.

Hill said that Spot On is also currently validating HemaSpot in support of a regulatory submission to the US Food and Drug Administration and the CE marking process, so that labs will be able to use the device to develop clinical diagnostic tests. "We expect to have that [FDA submission] finalized by the end of this year, and [to have the product] CE marked by the first quarter of next year," Hill said.

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