The Smart Magazine About Medical Technology Innovations
Greetings From the Lab
For this new edition of MedicalExpo e-magazine, we are opening the doors of the laboratory. You’ll find out how the rapid diagnostic tests can be amazing tools to diagnose diseases like HIV, malaria and even Zika. You’ll also discover an impressive, fully automated microbiology lab in action, as well as the immense proliferation of microscopy techniques that continues to reveal new wonders.
Rapid diagnostic tests are high quality, low-cost and easy-to-perform tests for use in resource-poor settings. Mainly used for HIV or malaria, they are frequently in the news with the development of rapid tests for Zika virus. We talked with Bill Rodriguez, chief medical officer at FIND, a non-profit organization that...
When it comes to lab automation,microbiology used to lag behind other laboratory disciplines – at least up to now. U.S. medical company Becton Dickinson has developed the fully automated sample processing system BD Kiestra TLA. This new technology, which is currently being tested at the Heidelberg University Hospital, is highly promising, particularly when dealing with the global challenge posed by microorganisms with multiple drug resistance.
If done manually, growing and identifying infecting agents in artificial culture media, such as agar plates, is a tedious job: From preparing the specimen, to streaking it across the culture medium with a wire loop, to providing it with the correct atmospheric conditions in an incubator, to labeling the plates and checking on them following a certain schedule, the necessary working steps can not only be time-consuming, but also prone to error. Although automated lab procedures would help improve the speed as well as the quality of such tasks, they are still somewhat of a novelty in medical microbiology.
“In contrast to for example clinical chemistry or hematology, where patient specimens have been processed in fully automated ways for several years, medical microbiology is one of the last areas of in vitro diagnostics, where manual procedures are still the rule—to a large part using the same techniques that were already established by Robert Koch,” a celebrated German physician and pioneering microbiologist, Dr. Detlef Storm, marketing manager for central Europe at BD Diagnostics Heidelberg, Germany, told us.
Lab automation (Courtesy of BD and Messe München)
To him, the main reason for this situation is that the methods of medical microbiology are relatively hard to standardize. After all, the microbial world is both tiny and vast.
BD Acquired Kiestra for a Total Lab Automation
While at least semi-automated systems have been available for almost 10 years, fully automated microbiology lab systems are still taking baby steps. Along with companies like bioMérieux and Copan, Becton Dickinson was one of the first companies to work on a fully automated solution. To that end, four years ago BD acquired Netherlands-based company Kiestra—a pioneer in automated microbial water analytics that developed a semi-automated medical microbiology lab.
The result of this cooperation is the new BD Kiestra Total Lab Automation (TLA), which fully automatizes and digitalizes all major working steps necessary to generate a microbiological test result from a patient specimen.
Here’s how it works:
When a barcoded test tube is inserted in BD Kiestra TLA, the system automatically recognizes the type of material, retrieves and labels the appropriate culture plates from integrated petri dish storage containers, opens the test tube to pick up an aliquot with a pipet, and is able to inoculate up to five plates at the same time, using a patented streaking technology.
“Properly streaking the specimen across the plate is critical to separating the different microbial colonies from one another. Therefore we developed the magnetic rolling bead technology: A small metallic blob rolls over the culture medium and can generate streak lengths of up to four meters,” said Storm about this feature, which has been shown to produce up to three to five times more single colonies compared with manual methods.
The BD Kiestra TLA fully automatizes all major working steps (Courtesy of BD)
The system then automatically transports the inoculated plates to the appropriate incubators, where each plate can be photographed up to every two hours. The lab technicians can then digitally review the plates on high-resolution monitors.
In April 2016, a BD Kiestra TLA was officially inaugurated at the microbiological laboratory of the Heidelberg University Hospital, led by Professor Dr. Klaus Heeg.
“We had two main reasons for implementing the system in our laboratory: The strong increase of test volumes as a quantitative aspect, and the fact that automated plate inoculation provides a significantly higher test resolution for microbic samples than manual methods as a qualitative aspect,” explained Dr. Stefan Zimmermann, Head of Division Bacteriology in Heeg’s laboratory. Zimmermann estimates that the test volumes at the laboratory have doubled in the last seven to eight years, mostly due to a surge in screenings for microorganisms with multiple drug resistances (MDR).
“Currently we receive about 700 samples every day from the different clinics. About 300 of those are nasal or rectal swabs for MDR screenings. These screenings have already been validated for routine testing on our BD Kiestra TLA along with all urine samples, which add up to approximately 100 samples per day,” said Zimmermann. Within the few months since the opening of BD Kiestra TLA, the lab was already able to reduce the time for most MRSA (Methicillin-resistant Staphylococcus aureus) screening results from about two days to 25 hours, thanks to the system’s ability to accurately manage inoculation times for every single culture plate.
According to Zimmermann another advantage of using the fully automated system is that lab technicians and physicians now have more time for clinically relevant tasks, such as interpreting findings or counseling clinicians about antimicrobial treatment. To better understand the effects of using BD Kiestra TLA on clinical outcomes, the lab will start conducting a crossover trial with two intensive care units, starting this fall.
The lab is also looking into training BD Kiestra TLA to become more intelligent.
“We hope that using a fully automated system will lead to quantifiable benefits for our patients, and eventually possibly even bigger scale effects such as reducing the incidence of antimicrobial resistance,” Zimmermann, who expects first preliminary results of the study in mid-2017, told us.
Together with Becton Dickinson, the lab is also looking into training BD Kiestra TLA to become more intelligent. In a first step, the system is supposed to learn to automatically identify Methicillin-resistant Staphylococcus aureus (MRSA) bacteria by recognizing the unique red hue they generate on chromogenic culture plates.
It was in the 17th century that Englishman Robert Hooke first used a primitive microscope to sketch magnified insects. Over three centuries later, the evolution of the microscope continues to reveal new wonders and underpin groundbreaking scientific research.
Today there is an immense proliferation of microscopy...
A new minimally invasive approach to treatessential tremor through ultrasound waves sent to the brain was approved last July by the FDA. This innovative system has the advantage of avoiding the risks of a brain surgery. But it has an ethical downside: It burns part of the brain cells. And there are no studies yet about the long-term effects.
Kristin “Sunny” Berry first noticed the tremor in her hands at school when she was 7 years old. It has gotten worse through the years, affecting her head and making it difficult to even eat, get dressed, or write. “Brushing my teeth was just a nightmare; I could write but nobody could read it,” she told to MedicalExpo e-mag during a phone interview.
She started looking on the Internet and found out about the HIFU procedure—High Intensity Focused Ultrasound treatment—performed by a couple of centers in the world, including Ohio State University Wexner Medical Center. She decided to apply. It was like a dream come true for Kristin. In mid-April, after a four-hour-session, she came back home without almost no shaking in her hands or head. “I could feel the difference right away—it was amazing,” she said.
Effects Are Immediate
The system is pretty simple. The patient puts on a helmet at the beginning of the procedure. This helmet has over a thousand ultrasound probes that will deliver the energy inside the brain. Then the person lies down on a MRI table so doctors can obtain images of the brain. When they get these pictures, they locate the area called the thalamus. It is a central structure of the brain that possesses over 120 components. One of these components is involved in generating the tremors.
Once doctors have identified this area, they apply ultrasound waves that traverse the skull and converge to the targeted area where they generate energy—about 1,000 watts that slowly heat up that part of the brain. By heating it up, the system burns away certain brain cells that are causing the tremor. The company InSightec manufactures the ExAblate Neuro, the focused ultrasound device approved by the FDA.
“The patient receives no anesthesia—they are awake the whole time and interacting with us,” explained Dr. Ali Rezai, director of the Center for Neuromodulation at Ohio State’s Neurological Institute. “We do tests first. So we deliver small amounts of the energy to see if there’s any benefits or any side effects. If the patient doesn’t report any problem after 10 or 15 minutes, then we increase the energy.” The patient sees the changes directly on the MRI table.
Not a First- or Even Second-Line Therapy
“This new technique is advantageous because it is basically performing a brain surgery without cutting the skin or opening the bone. It’s minimally invasive,” said Dr. Rezai. Still, one major issue remains: The ultrasound waves are actually burning a part of the brain, and the cells that are burnt won’t regenerate.
Before and after writing examples (Courtesy of Ohio State University Wexner Medical Center)
Dr. Rezai acknowledges that it is an important point. “That’s why we don’t do this approach as a first-line therapy or even second-line. We are talking about patients who have tried various medications and other treatments, and despite the best attempts for years their tremor has become so severe that they have difficulty with basic activities like eating, dressing themselves, writing, working. So it comes to a point where they become very disabled.”
According to him, burning the brain or the nerves is commonly used worldwide for example to treat chronic pain. Kristin, for her part, “tried not to think too much about that.” “It was worth it and I would do it again” if needed.
Plans to Treat Depression or Compulsive Disorder
Rezai acknowledged, “Yes, if you don’t target exactly in the precise area, it’s possible that the patient may have problems in terms of sensation loss, or difficulty speaking or moving, but it’s extremely rare. The safety profile is very strong with this,” he added.
Side effects included sensory and gait disturbances.
A randomized trial was published in The New England Journal of Medicine on August 25. In this study involving 76 patients with medication-refractory essential tremor, transcranial-focused ultrasound thalamotomy significantly reduced hand tremor at three months, and the effect persisted during the 12-month study period. Side effects included sensory and gait disturbances. But there are no studies yet to tell what could be the effects over two, three, or five years.
“I don’t think there could be a side effect because if there was a big problem you would see it right away on the patient, but the issue could be the tremor coming back,” said Dr. Rezai. According to him, this approach is CE-certified for Parkinson’s disease. Researchers are now looking into ways to use it to treat epilepsy, depression or even obsessive-compulsive disorder.
“At best, it’s a co-symbol,” said Jensen, who has combed paintings and old chemistry texts in search of data to date the test tube and other apparatus used in chemistry labs.
If you think the test tube dates back to alchemy, wrong again, said Jensen, who has been able to trace the test tube back only to the first decade of the 19th century. Actually, you’d probably be thinking of spherical vessels with a long downward-pointing neck known as the retort, glass or copper vessels used in distillation. (The idiom “snappish retort” may refer to the vessel.)
Liquids are placed in the retort to be heated. The neck acts as a condenser, allowing the vapors to condense, flow along the neck and be collected underneath, according to Wikipedia. In the case of alchemy, you would actually be thinking instead of a retort. No self-respecting alchemist would’ve been without one.
Jensen said, “Virtually every modern-day artistic depiction of an alchemist will feature a retort as the centerpiece of the alchemist’s laboratory,” he said. “Perhaps no single piece of laboratory apparatus is more intimately associated in popular culture with the practice of chemistry than is the retort.”
A Snappy Retort
1494 (Painting of chemist William Jensen – Oesper Collections, University of Cincinnati)
A retort is depicted on the Boy Scouts of America’s chemistry merit badge, said Jensen. Likewise, the insignia for the Chemical Corps of the United States Army incorporates retorts.
Retorts first appeared in the literature dealing with distillation sometime in the 14th or 15th century, he said in an article entitled “A Snappy Retort” in Notes from the Oesper Collections (Museum Notes, January/February 2013, 1-6).
Common laboratory apparatus, including flasks (think Walter White, the high school chemistry teacher turned meth kingpin), beaker (think the Muppets) and retorts (think Merlin) before the 19th century was flawed.
Jensen said that’s because it did not have a high melting point; was not resistant to being destroyed by water, alkalis and acids; was not colorless and transparent; and was not resistant to thermal and mechanical stress.
Jensen has traced the creation of the test tube to the beginning of the 19th century. He said test tubes were used to heat chemicals, which, based on the colors that were seen, allowed chemists to identify chemicals.
Here Comes the Pyrex
Throughout the century, innovations in glassmaking, such as making it thin with tough glass, made the modern test tube possible.
Test tube rack from 1880s (Courtesy of Oesper Collections, University of Cincinnati)
In 1915, Corning Glass introduced Pyrex, which was superior in withstanding mechanical shock, Jensen wrote in his Ask the Historian column entitled “The Origin of Pyrex” (J. Chem. Educ., 2006, 83, 692-693). Pyrex first was used in cookware, but soon was applied to lab glassware. Test tubes are hanging in there. Retorts have been in decline for more than a century.
“Ironically, despite its continued use as a symbol for the practice of chemistry, the retort had already begun to disappear from day-to-day laboratory practice by the early decades of the 20th century…”, he said.
Imagine a patient with a heart valve problem—not an emergency situation, but a complex, ongoing case, with the quality of the patient’s life going down significantly. First of all, an exact patient assessment is crucial to decide for the optimal treatment. Based on this information, an interdisciplinary heart team decides whether surgical or minimally invasive intervention is the most appropriate treatment approach.
In those cases, a minimally invasive procedure is the best choice to treat structural heart diseases. With minimally invasive procedures, open thorax surgery is not needed. The patient would probably avoid general anesthesia which translates into shortened recovery time and therefore less time to be spent at the hospital.
The ACUSON SC2000 (Courtesy of Siemens Healthineers)
“Minimally invasive procedures are an alternative for some patients, but the physicians face also some challenges,” explained Doris Pommi, head of marketing in cardiology at Siemens Healthineers, during a phone interview with MedicalExpo e-mag. “Physicians treat the patient by inserting a catheter via a femoral or apical access for heart valve treatment. Therefore, the physicians don’t see the [heart] valve physically, like in an open surgery, so the need of excellent image quality, information about anatomy and physiology, and guidance during the procedure is crucial,” she added.
Devices become smaller and the material they’re made of could be difficult to visualize. For an optimal outcome, it is necessary to assess the correct placement, deployment and function of the device. That’s where Siemens Healthineers comes into the game. The German company offers to “provide the imaging modalities and tools to support the assessment of the patient before the procedure”, to “guide the exact placement during the procedure” and finally to provide imaging and tools to support after the procedure if everything is working well.
Therapy: Checking the Placement of the Implant Immediately
These are two examples for the diagnosis and assessment step:
The ACUSOM SC2000 Prime combines two technologies: the ultrasound system that can produce 3-D transesophageal echocardiography full-volume color Doppler images of the heart and blood flow, and the integrated eSie Valves analysis software that supports precise measurements of the individual heart valves in just seconds.
Dual-source CT scanners from Siemens Healthineers make it possible to perform CT imaging with low doses of radiation. The high rotational speed of the SOMATOM Force and the resulting temporal resolution, make it unnecessary for patients to hold their breath during the scan or to take medications to regulate their heartbeat, explained Siemens Healthineers in a press release.
The SOMATOM Force (Courtesy of Siemens Healthineers)
Finally, the real-time 3-D ultrasound imaging provided by the ACUSON SC2000 Prime comes into play with minimally invasive mitral valve therapy, since its full-volume color Doppler function enables the assessment of the implantimmediately, while the patient is still on the operating table. The heart team sees immediately, if the treatment was successful.
The whole clinical pathway needs “very good teamwork,” said Pommi.