Issue 74

News

“Lab on a Chip” Could Detect Disease-Causing Bacteria

McGill University researchers have created a new type of “lab on a chip” that has the potential to become a clinical tool capable of detecting minute quantities of disease-causing bacteria within a few minutes.

This new type of “lab on a chip” developed by McGill University scientists has the potential to become a clinical tool capable of detecting very small quantities of disease-causing bacteria in just minutes.

The device built by Sara Mahshid, Assistant Professor in the Department of Bioengineering at McGill, is composed of nano-sized “islands,” about one-tenth of the thickness of a single human hair, which serve as bacterial snares or traps.

In partnership with colleagues from the University of Toronto, Professor Mahshid’s team was able to show that the system is capable of examining very tiny volumes of culture media containing bacteria such as E. coli and a strain of S. aureus resistant to methicillin, an antibiotic meant for treating bacterial infections.

"Speed is of the essence because some bacterial infections can cause serious health problems and sometimes lead to death. With a fluorescent microscope, the device we’ve developed can confirm the presence of bacteria in just a few minutes. I hope one day clinicians will use our device to deliver faster diagnostics, start treatment much more quickly and, ultimately, save lives."

Mahshid and her team, who recently published their research in the journal Small, now hope to try out their device on clinical samples, a required step before doctors are able to employ such a device in a hospital site. Theoretically, this new lab-on-a-chip, which is comparatively economical and easy to make, could also examine samples from blood, urine, or nasal swabs.

The Essenlix iMost blood test using iPhone technology for on-demand testing

Essenlix, a New Jersey-based company, is developing a system that uses an iPhone and an attachment to run lab samples on-the-go.

"You basically have a mobile chemical biological lab in your hand," Stephen Chou, a professor of electrical engineering at Princeton University, said.

Essenlix's system, dubbed the iMOST (short for "Instant Mobile Self-Test"), consists of a few different components: there's an app, an attachment , a cartridge for the sample, and of course the iPhone itself. The attachment sits over the iPhone's camera and flash. The test starts with a finger-prick. The first drop of blood gets wiped away, but the second gets put on a thin plastic cartridge. Once that's done, the cartridge is loaded into the green attachment, and the test is run in a matter of seconds, leveraging the insides of the iPhone including the flash and camera.

To vet Essenlix's system, the team ran clinical trials comparing the new technology to traditional devices. In two trials of 92 patients total run at Hunterdon Hematology Oncology in New Jersey, Essenlix tested patients with both the standard machine and its blood test. In the end, there was on average a 6% difference between Essenlix's white and red blood cell counts and what traditional machines found, and a 3% difference in hemoglobin measurements, all within the FDA requirements for allowable total error.

Point-of-Care

Portable device capable of diagnosing within ten minutes mild traumatic brain injury, using a single drop of blood

Researchers from the University of Geneva (UNIGE), in collaboration with the Hospitals of Barcelona, Madrid and Seville, have developed a small device that analyses the level of proteins in the blood and allows, using a single drop of blood, to diagnose the possibility of a mild traumatic brain injury.

"We wondered if it was possible to isolate certain proteins whose presence in the blood increases in the event of mild traumatic brain injury," explains Jean-Charles Sanchez, professor at the Department of Internal Medicine of Specialties and the Biomarkers Centre of the Faculty of Medicine of the UNIGE. "Our idea was to find a way to do a quick examination that would allow, during a boxing or American football match for example, to determine whether the athlete can return to the field or if his condition requires hospitalization."

During a shock on the head, some brain cells are damaged and release the proteins they contain, increasing their level in the blood. Scientists at UNIGE and Spanish hospitals then compared the blood of patients admitted for mild traumatic brain injury but diagnosed as negative with that of patients actually suffering from a brain lesion. Using proteomic analyses, which can quantify thousands of proteins simultaneously and observe variations in their levels in the blood, they gradually isolated four molecules indicating the presence of a brain injury: H-FABP, Interleukin-10, S100B and GFAP. "We have noticed that the H-FABP level alone makes it possible to confirm that there is no risk of trauma in one third of patients admitted after a shock," enthuses Jean-Charles Sanchez. The rest of the patients will have to undergo a CT scan to confirm the diagnosis.

It was still necessary to develop a device that could be used everywhere, quickly and simply, and that could be available in pharmacies or sports halls. "When a person has an accident in the mountain, few practices can do a CT Scan," notes the Geneva researcher. His team has developed a rapid diagnostic test (POCT) called TBIcheck, inspired by the principle of pregnancy testing: by placing a single drop of blood on the well of a small 5cm plastic case, the patient knows within 10 minutes whether there is a risk of mild trauma, namely whether or not his H-FABP level is higher than 2.5 nanograms per millilitre of blood. "If a lane appears, the injured person must go to a hospital for a CT scan, if there is nothing, he can go home safely!" Jean-Charles Sanchez says. In case of doubt when reading the result, a small reader, the Cube Reader, can be installed on TBIcheck. It will display the word "positive" or "negative" and send the result to the patient's or caregiver's smartphone via Bluetooth.

Clinical Chemistry

In newborns, two-screen approach better identifies congenital hypothyroidism

A two-screen approach to diagnostic testing for congenital hypothyroidism, performed in newborns during the first 48 hours after birth and again at age 7 to 28 days, better identified missed cases of the disease vs. lowering the diagnostic threshold for a single test, according to an analysis published this week in the CDC’s Morbidity and Mortality Weekly Report.

Initial screenings for congenital hypothyroidism are typically performed 24 to 48 hours after birth; however, 14 states, including Utah, perform a routine second screen at approximately age 2 weeks, the researchers wrote, and an analysis of Utah data suggests a second screening identifies missed cases of the condition. “The goal of screening is not to miss cases, while avoiding overwhelming the health care system with false-positive screens requiring unnecessary follow-up and diagnostic testing,” Jones and colleagues wrote. “In Utah, a two-screen program supports this goal.” In Utah, all infants receive two screenings for primary congenital hypothyroidism even if the first screen is positive for the disease. In Utah, any TSH value of at least 40 µIU/mL is considered abnormal for either a first or second screen, and elevated screening results are followed by diagnostic testing.

Jones and colleagues analyzed data from 123 infants with confirmed cases of congenital hypothyroidism, identified in Utah between 2010 and 2016, who underwent two screenings for the disease. Within the cohort, 98 cases were identified by the first screen and 25 cases were identified in the second screening. Researchers stratified infants by two groups: those with an abnormal first screen (group 1) and those with a normal first screen but abnormal second screen (group 2), calculating mean TSH concentrations for both groups. Researchers performed a retrospective cutoff analysis to determine whether all group 2 cases could be identified by a single screen, analyzing the number of false positives and false negatives as a function of adjusting the first screening cutoff value to a range between 5 and 40 µIU/mL.

Researchers found that, among group 2 infants, TSH concentrations were lower on the first screen, with all infants having concentrations below the 40 µIU/mL cutoff value, but with TSH values above the cutoff value on the second screen. Compared with all infants with and without congenital hypothyroidism, TSH levels for group 1 and group 2 infants were elevated for the first and second screenings, according to researchers. The researchers determined that a moderate cutoff adjustment from 40 µIU/mL to 20 µIU/mL would have resulted in approximately 27,600 false-positives cases and 11 missed cases. “To ensure that all group 2 cases were detected through a single screen, a TSH cutoff values of 5 µIU/mL would have been necessary, which would have resulted in 282,850 false-positive cases or approximately 79% of the screened population, the researchers wrote.

The researchers concluded that the study underscores the utility and power of a two-screen approach in identifying congenital hypothyroidism cases with a normal TSH concentration on the first screen but an elevated TSH concentration on the second screen.

Transfusion Medicine

Plasma during air transport may benefit those at risk for hemorrhagic shock

The use of thawed plasma during prehospital air medical transport appeared safe and led to lower 30-day mortality than standard resuscitation among patients at risk for severe hemorrhage, according to results from the phase 3 Prehospital Air Medical Plasma, or PAMPer, clinical trial.

“These results have the power to significantly alter trauma resuscitation, and their importance to the trauma community cannot be overstated,” Jason L. Sperry, MD, MPH, assistant professor in the departments of surgery and critical care medicine at Clinical and Translational Science Institute of University of Pittsburgh, said in a press release. “This is the first trial in a quarter century to have the potential to alter prehospital care so considerably.”

For this study, researchers used a single-stage cluster randomization scheme due to the limited availability and short shelf life — 5 days — of universal donor thawed plasma.

Sperry and colleagues randomly assigned air medical bases from nine medical institutions to administer two units of plasma (n = 230) or standard-of-care resuscitation (n = 271) at 1-month intervals to patients transported via air medical transport between May 2014 and October 2017.

All patients had suffered blunt trauma — with at least one episode of hypotension and tachycardia, or severe hypotension — prior to arrival of air medical transport or any time before arrival at the trauma center.

Mortality at 30 days served as the study’s primary outcome. Secondary outcomes included mortality at 24 hours and in-hospital mortality; volumes of blood components and resuscitation fluid given within 24 hours after study enrollment; multiorgan failure; incidence of acute lung injury-acute respiratory distress syndrome, transfusion-related acute lung injury or nosocomial infection; indexes of coagulopathy; and results of thromboelastography.

The rate of 30-day mortality was 23.2% among patients who receive plasma, compared with 33% among patients who received standard resuscitation, for a difference of 9.8% points (95% CI, 18.6 to 1).

Read more about this research by clicking on the article title above.

Research and Education Round Up - July 2018

Canadian Blood Services released its July edition of Research and Education Round Up this week.

Topics include:

New Resources

New Publications

Read the entire issue by clicking on the title above.

Microbiology

Emergency departments can be an effective venue for hepatitis C virus testing

Boston Medical Center has shown that testing for the Hepatitis C Virus (HCV) outside the typical high-risk population can be successfully implemented in an emergency department setting, resulting in more patients being screened, diagnosed and treated who might not have been otherwise. The new study, published in Academic Emergency Medicine, is the first report of a large scale emergency department program, which increased the monthly rate of HCV screening by more than 6,000 percent by testing regardless of patients' perceived risk for the disease.

The researchers collected data from a three month period, between November 2016 and January 2017, and found that HCV tests were performed in BMC's emergency department on 3,808 patients, an average of 1,269 per month. That was a 6,950 percent increase from the 2015 to 2016 monthly average of 18 HCV screenings per month. Patients had to be at least 13 years old, were already undergoing blood testing for clinical purposes, and gave authorization for HCV antibody and reflex confirmatory RNA tests.

Thirteen percent (504 cases) of the initial HCV tests were positive, and of those, 97 percent (493) had a follow up RNA test performed. Active infections were confirmed positive for 292 cases for an overall HCV positivity rate of almost 8 percent. Of those with an active infection, 155 cases, or 4 percent of all individuals tested, fell outside of the Center for Disease Control and Prevention's birth cohort for increased risk for HCV.

The study also attempted to link patients with active infections to follow up care; appointments were scheduled for 102 patients (approximately 35 percent), and ultimately, 66 patients made a care visit (22 percent of all active infection patients). "Those 66 patients that were connected to care through our program demonstrate the importance of increasing screening rates for HCV infection," said Perkins.

Research

Researchers Solve Mystery of How ALL Enters the Central Nervous System

A deadly feature of acute lymphoblastic leukemia (ALL) is its invasion of the central nervous system. ALL in the central nervous system is very difficult to treat, because most drugs are blocked from the organ system due to a "blood-brain barrier" designed to protect the brain. How cancer cells enter the central nervous system has been an unanswered question for researchers and clinicians for decades.

Now, a research team led by Duke Cancer Institute scientists found that this blood cancer infiltrates the central nervous system not by breaching the blood-brain barrier, but by evading the barrier altogether. Publishing in the journal Nature, the researchers describe how the cancer cells are uniquely equipped with receptors that can grasp scaffolding proteins on the outside of blood vessels like fire poles, riding them down from the bone marrow through membranes into the space filled with cerebral-spinal fluid. “It’s a very unexpected way for cells to travel into the central nervous system,” said Dorothy Sipkins, M.D., Ph.D., associate professor in Duke’s division of Hematologic Malignancies and Cellular Therapy. Sipkins is the senior author of the study, which is published online July 18.

After perfecting a way to view the brains of mice in real time, she still could not see how ALL cells crossed into the central nervous system. More experiments followed, but the mystery remained unsolved, even as the assumption of a blood-brain breach continued to guide both care and research for advanced ALL. Then a key finding emerged from experiments on a drug that Sipkins’ lab was testing. Mice receiving the drug were not becoming paralyzed from advanced ALL disease, which is what usually happens to the animals when cancer cells infiltrate the central nervous system. Instead, the cancer remained in the animals’ bone marrow.

Upon further analysis, Sipkins found that the drug itself did not cross the blood-brain barrier, so it wasn’t activating a therapeutic response in the cerebral spinal fluid. That meant that the drug was somehow preventing the cancer cells from migrating into the central nervous system.

“When we dissected the spines and the vertebrae that surround the spinal cord, we noticed this strange thing: you could see all the leukemia cells in the vertebral bone marrow and it looked like they were streaming through a channel at the bone surface straight into the spinal cord,” Sipkins said. But the cancer cells were not simply chewing through the bone. Instead, the researchers found, the ALL cells carry an abundance of receptors for a protein called laminin, which surrounds blood vessels and nerves to help facilitate cell migration. Tiny blood vessels pass directly through the vertebrae to the meninges tissue that lines the spinal cord and brain. The ALL cells were grabbing onto the laminin surrounding these blood vessels and zipping down into the meninges region where cerebral spinal fluid circulates.

Thank you!

We appreciate that you have taken the time to read LabBuzz. This is a CSMLS venture to provide relevant medical laboratory news to its members.

We need your help to grow this newsletter! Please pass along the subscription link to any colleague you think would benefit from hearing about med lab news.