February 21, 2024 | A revolution is underway in the diagnostics world that is reminiscent of what transpired in the computing field before the advent of PCs and smartphones, according to Mehdi Javanmard, CEO and cofounder of RizLab Health (Princeton, New Jersey). The unimagined possibilities of today will come from democratizing technology so that instead of sending patients to the lab, the lab will get sent to patients—and, ultimately, be available to them in the form of at-home testing kits.
Already on the horizon is a handheld white blood cell analyzer, known as the CytoTracker Leukometer, which RizLab Health has been on a mission to build since its founding in 2018. RizLab (a spinoff of Rutgers University, where Javanmard is a professor in the department of electrical and computer engineering) has manufactured the device and is now working on getting it cleared for marketing by the Food and Drug Administration (FDA).
“We set out with the goal of solving the holy grail of medicine—the ability to take a drop of blood from patients and analyze it in a way to guide clinical decision-making and improve patient outcomes,” says Javanmard. That looks entirely possible, based on results of a clinical validation study that published recently in PLOS One (DOI: 10.1371/journal.pone.0296344).
When pitted against a gold-standard benchtop hematology analyzer, the device produced highly similar white blood cell counts (at least 97% accuracy) and returned results in a matter of minutes. This suggests its suitability for point-of-care testing, to for example triage patients in the emergency room who might have sepsis or to help oncologists determine whether cancer patients need a white blood cell stimulant, Javanmard says. The portable device might also improve medication adherence among schizophrenia patients who must undergo regular testing of their neutrophil levels (once a week initially) before obtaining a prescription for clozapine, he adds.
While others have tried without success to develop tests for detecting multiple conditions with a single drop of blood, CytoTracker narrowly focuses on total white blood count and the two key subtypes of neutrophils and lymphocytes. The three data points collectively have the biggest impact in monitoring and guiding treatment for various infectious diseases, cancers, and psychiatric conditions, Javanmard says.
Like glucometers and ubiquitous consumer electronic devices such as cellphones and smartwatches, the CytoTracker is “fully electronic,” he says. “There are no optics or moving parts, and that is what allows it to be so small and inexpensive at the same time.”
Javanmard describes the detection mechanism as a microchip on a test strip with a channel thinner than the diameter of a human hair through which cells flow one at a time over electrical sensors, getting scanned as to whether they are neutrophils or lymphocytes while also being quantified.
The predominant workflow for blood testing today is highly inefficient, involving phlebotomy with tubes of collected blood sent to a lab for analysis, which at a high-end facility might take an hour or two but more than a day or two in many rural settings, he continues. Handheld and transportable devices can enable near-patient testing, streamlining workflows for patients and providers and enabling faster times to clinical decisions and better health outcomes.
Soon, CytoTracker might logically find its way into a range of care settings, among them hospitals, community pharmacies, and skilled nursing facilities, as well as ambulances.
Since RizLab Health has successfully implemented good manufacturing practices for CytoTracker, the company plans to launch clinical trials that will become part of its submission package to the FDA for 510(k) marketing clearance of the device. The trials will enroll hundreds of patients over multiple sites in different parts of the country, says Javanmard. For the clinical validation study, the partnering sites were the Rutgers Robert Wood Johnson Medical School Clinical Research Center in New Jersey and the Baylor College of Medicine Department of Emergency Medicine in Texas.
The trial will again attempt to demonstrate equivalency to a predicate device, or a device that is already FDA-cleared with similar functionality, Javanmard says. Getting approval for in-clinic use of CytoTracker is intended to be an “intermediate step” for evidence-generating purposes, the longer-term goal being getting FDA clearance for home use.
Beyond situations where the total white blood cell count is important, Javanmard and his team are actively exploring use cases where neutrophil and lymphocyte counts matter—notably, in discriminating between viral and bacterial infections. Antimicrobial resistance is the third leading cause of death worldwide, according to a 2022 report in The Lancet (DOI: 10.1016/S0140-6736(21)02724-0). “It is here, and it is real,” he says.
The key driver of antimicrobial resistance in humans is overuse of antimicrobials and, according to the Centers for Disease Control and Prevention, at least 30% of antibiotics prescribed in doctor’s offices and emergency departments are either inappropriate or unnecessary, Javanmard shares. The pressure to prescribe antibiotics sometimes comes from patients themselves, and often from the parents of sick and suffering children.
The second generation of CytoTracker will incorporate artificial intelligence (AI) software to discriminate between viral and bacterial infections, helping doctors know, on the spot, whether antibiotics are needed, he says. This will soon be demonstrated in a larger study population where machine learning will be used for data analysis.
Neutrophils are the “frontline defenders” against bacterial pathogens and high numbers of them as a percentage of the total white blood cell count tend to signal bacterial infections, continues Javanmard. In contrast, a higher proportion of lymphocytes can be indicative of a viral infection.
AI can enhance the ability to tell the two infection types apart, based on additional results from the latest study that have not yet been published. “We’ve explored different types of [machine learning] algorithms and found that even a lot of the off-the-shelf algorithms can do a pretty good job,” he says.
Unforeseeable Applications
The handheld white blood cell tracker has epidemic-level potential in healthcare when it comes to countering the overuse of antibiotics that are causing new strains of bacterial pathogens to emerge, as well as enabling antimicrobial stewardship to minimize unnecessary use of antibiotics while ensuring they are administered to patients who need them within their window of effectiveness, says Javanmard. It likewise potentially holds value for risk stratification of sepsis patients in emergency rooms and intensive care units.
During the height of the COVID pandemic, researchers also discovered that abnormal neutrophil-to-lymphocyte ratios can be a useful predictor of patient risk and infection severity, he adds. Unknowns about who and how to treat patients with the mysterious virus were major concerns before vaccines came out to prevent or at least tamp down symptoms and deaths.
The diagnostics revolution he envisions follows a similar trajectory as the evolution of computers, which in the 1960s and 1970s were machines the size of two rooms and required inserting punch cards to implement a simple program. The turnaround times were super-slow and no one—not even Ken Olsen, chairman of computer-maker Digital Equipment Corporation—saw any reason why an individual would want a personal computer in their home.
“And look where we are today,” Javanmard says. “We wear computers way more powerful than that on our wrist. We not only have laptops; we have amazingly powerful phones in our pockets. Even the inventor of the computer probably couldn’t have imagined [those] possibilities.”
Likewise, he predicts, novel and unforeseeable applications for diagnostic technologies are going to emerge as more people gain access. “We’ll do near-patient testing and, ultimately, get labs in the hands of patients.”