Small handheld device uses sound waves to detect certain clinical laboratory biomarkers in blood samples
University of Colorado Boulder researchers have developed a novel technology that uses sound waves to test for biomarkers in blood samples. In addition to being very easy to use, the handheld device is portable, highly sensitive, and delivers results in minutes. Though not ready for clinical use, this is yet another example of how researchers are developing faster diagnostic tests that can be performed in near-patient settings, and which do not have to be done in core laboratories, shortening time to answer.
The small instrument—referred to as an “acoustic pipette”—delivers sound waves to tiny particles within the device called “functional negative acoustic contrast particles” (fNACPs). These particles are cell-sized balls that can be customized with different coatings to identify specific biomarkers—such as viruses or proteins—in tiny blood samples, according to a news release.
To operate the device, the custom fNACPs are mixed with a drop of blood and then placed inside the acoustic pipette. The mixture is then blasted with sound waves, which forces particles carrying certain biomarkers to one side of the chamber where they are trapped while the rest of the blood is expelled. The captured biomarkers are then labeled with fluorescent tags and examined with lasers to determine how much of a specific biomarker is present.
“We’re basically using sound waves to manipulate particles to rapidly isolate them from a really small volume of fluid,” said Cooper Thome (above), PhD candidate in Chemical and Biological Engineering at UC Boulder and first author of the study in a news release. “It’s a whole new way of measuring blood biomarkers,” he added. Should further studies validate this approach, clinical laboratories may be able to use this technology to perform diagnostic tests with smaller volumes of patient samples. (Photo copyright: University of Colorado Boulder.)
Blood Testing Quickly and in Multiple Settings
To test their invention, the UC Boulder researchers examined antibodies against a protein called ovalbumin, which is found in egg whites and often used in the development of various vaccines. The scientists discovered that their device could detect the antibodies even in low amounts.
Current rapid tests known as lateral-flow assays can detect specific biomarkers in blood or urine samples but cannot determine how much of the biomarker is present. Enzyme-linked immunotherapy assays (ELISA), the leading clinical laboratory blood test, requires expensive equipment and can take hours to days for results to be received.
With UC Boulder’s new handheld device, tiny blood samples collected from a single finger prick could ensure accurate test results are available quickly at the point of care as well as outside of traditional healthcare settings. This would greatly benefit people in developing nations and underserved communities and may help ease test anxiety for individuals who are apprehensive about traditional blood tests.
“We’ve developed a technology that is very user friendly, can be deployed in various settings, and provides valuable diagnostic information in a short time frame,” said Wyatt Shields IV, PhD, Assistant Professor, Department of Chemical and Biological Engineering, UC Boulder, and senior author of the research in the news release.
“In our paper, we demonstrate that this pipette and particle system can offer the same sensitivity and specificity as a gold-standard clinical test can but within an instrument which radically simplifies workflows,” he added. “It gives us the potential to perform blood diagnostics right at the patient’s bedside.”
The graphic above, taken from UC Boulder’s published paper, illustrates how “fNACPs capture target biomarkers from whole blood samples. fNACPs are purified from blood components by acoustic trapping and captured biomarkers are labeled with a fluorescent antibody within the acoustic pipette. fNACP fluorescence is then measured to determine biomarker presence and concentration.” (Graphic/caption copyright: University of Colorado Boulder.)
Not Like Theranos
The authors of the UC Boulder study are cognizant of some skepticism surrounding the field of biosensing, especially after the downfall of Theranos. The scientists insist their technology is different and based on systematic experiments and peer-reviewed research.
“While what they (Theranos) claimed to do isn’t possible right now, a lot of researchers are hoping something similar will be possible one day,” said Thome in the news release. “This work could be a step toward that goal—but one that is backed by science that anybody can access.”
The device is still in its initial proof-of-concept stage, but the UC Boulder scientists have applied for patents for the apparatus and are searching for ways to scale its use and expand its capabilities.
“We think this has a lot of potential to address some of the longstanding challenges that have come from having to take a blood sample from a patient, haul it off to a lab, and wait to get results back,” Shields noted.
More research, studies, and regulatory reviews will be needed before this technology becomes available for regular, widespread use. But UC Boulder’s new blood testing device is another example of a research team using novel technology to test for known biomarkers in ways that could improve standard clinical laboratory testing.
Theranos founder and former CEO continues down the path she began by defrauding her investors and lying to clinical laboratory leaders about her technology’s capabilities
As a result of the ban, Holmes is “barred from receiving payments from federal health programs for services or products, which significantly restricts her ability to work in the healthcare sector,” ARS Technica reported.
So, Holmes, who is 39-years old, is basically banned for life. This is in addition to her 11-year prison sentence which was paired with $452,047,200 in restitution.
“The exclusion was announced by Inspector General Christi Grimm of the Department of Health and Human Services’ Office of Inspector General,” ARS Technica noted, adding that HHS-OIG also “excluded former Theranos President Ramesh “Sunny” Balwani from federal health programs for 90 years.” This is on top of the almost 13-year-long prison sentence he is serving for fraud.
“The Health and Human Services Department can exclude anyone convicted of certain felonies from Medicare, Medicaid, and Pentagon health programs,” STAT reported.
“Accurate and dependable diagnostic testing technology is imperative to our public health infrastructure,” said Inspector General Christi Grimm (above) in an HHS-OIG statement. “As technology evolves, so do our efforts to safeguard the health and safety of patients, and HHS-OIG will continue to use its exclusion authority to protect the public from bad actors.” Observant clinical laboratory leaders will recognize this as yet another episode in the Elizabeth Holmes/Theranos fraud saga they’ve been following for years. (Photo copyright: HHS-OIG.)
Why the Ban?
“The Office of Inspector General (OIG) for the Department of Health and Human Services (HHS) cited Holmes’ 2022 conviction for fraud and conspiracy to commit wire fraud as the reason for her ban,” The Hill reported.
“False statements related to the reliability of these medical products can endanger the health of patients and sow distrust in our healthcare system,” Grimm stated in the HHS-OIG statement, which noted, “The statutory minimum for an exclusion based on convictions like Holmes’ is five years.
“When certain aggravating factors are present, a longer period of exclusion is justified,” the statement continued. “The length of Holmes’ exclusion is based on the application of several aggravating factors, including the length of time the acts were committed, incarceration, and the amount of restitution ordered to be paid.”
Rise and Fall of Elizabeth Holmes
Readers of Dark Daily’s e-briefs covering the Holmes/Theranos fraud saga will recall details on Holmes’ journey from mega success to her current state of incarceration for defrauding her investors.
In November 2022, she was handed an 11-year prison sentence for not disclosing that Theranos’ innovative blood testing technology, Edison, was producing flawed and false results. Theranos had “raised hundreds of millions of dollars, named prominent former US officials to its board, and explored a partnership with the US military to use its tests on the battlefield,” STAT reported.
To get Holmes physically into prison was a journey unto itself. At one point, evidence showed her as a potential flight risk. “In the same court filings, prosecutors said Holmes and her partner, William Evans, bought one-way tickets to Mexico in December 2021, a fact confirmed by her lawyers,” Dark Daily’s sister publication The Dark Report revealed in “Elizabeth Holmes’ Appeal Questions Competence of CLIA Lab Director.”
Drama around her move into prison continued. “The former CEO’s attorneys are making last-minute legal moves to delay her prison sentence while she appeals her guilty verdict,” Dark Daily reported.
At the same time, Holmes appeared to be on a mission to revamp her public image.
In the Times piece, Holmes talked about her plans to continue to pursue a life in healthcare. “In the story, Holmes contended that she still thinks about contributing to the clinical laboratory field. Holmes told The Times that she still works on healthcare-related inventions and will continue to do so if she reports to prison,” The Dark Report covered in “Elizabeth Holmes Still Wants ‘To Contribute’ in Healthcare.”
In the meantime, her legal fees continued to mount beyond her ability to pay. “Holmes’ prior cadre of lawyers quit after she could not compensate them, The Times reported,” The Dark Report noted. “One pre-sentencing report by the government put her legal fees at more than $30 million,” according to The New York Times.
Apparently, this closes the latest chapter in the never-ending saga of Elizabeth Holmes’ fall from grace and ultimate conviction for defrauding her investors and lying to healthcare executives, pathologists, and clinical laboratory leaders.
Prior to that, however, the FDA had already announced its intention to issue a proposed rule giving the agency regulatory oversight of LDTs.
“The FDA has continually supported the passage of the VALID Act by Congress,” attorney Charles Dunham IV, a Shareholder at Greenberg Traurig LLP in Houston, told Dark Daily. “In fact, there is speculation that the VALID Act will be attached to the Pandemic and All Hazards Preparedness Act as it moves through Congress.”
“The FDA may not actually proceed with promulgating rules to regulate LDTs if it is concerned it will not be successful in court if the rules are challenged, which would happen,” said attorney Charles Dunham IV (above), a Shareholder at Greenberg Traurig, LLP. Clinical laboratory leaders can learn more from Dunham during a panel discussion at next week’s 2023 Executive War College on Diagnostics, Clinical Laboratory, and Pathology Management in New Orleans. (Photo copyright: Greenberg Traurig LLP.)
Arguments For and Against FDA LDT Regulation of LDTs
Supporters of the VALID Act contend that putting LDTs under FDA regulation will lead to improved patient safety and less review for low-risk tests. Their argument is that LDTs should undergo the same FDA review and approval process as other medical devices.
Hospital laboratory managers and pathologists—particularly in academic medical center laboratories—have largely opposed FDA regulation of LDTs. They prefer to keep the current setup under which lab-developed tests are validated under the Clinical Laboratory Improvement Amendments of 1988 (CLIA). They argue that FDA intervention will slow down development of new tests.
In response, an FDA official indicated during the American Clinical Laboratory Association’s (ACLA) annual meeting on March 1 that the federal agency plans to issue a proposed rule to regulate LDTs, BioWorld reported. That rulemaking has not yet emerged. It’s possible the FDA will wait and see what happens in Congress with the VALID Act.
“Some legal experts have suggested that one significant new legal challenge FDA may face is the Supreme Court’s West Virginia v. EPA decision last summer that limited the ability of the EPA to cap power plant emissions by regulation due to the EPA’s lack of explicit congressional authority to do so,” said Gee, who also will appear on the Executive War College legal panel next week.
“The West Virginia v. EPA ruling provides support for those in the clinical lab industry who point to the FDA’s lack of clear statutory authority to regulate LDTs and therefore fundamentally disagree with FDA’s longstanding position that LDTs are medical devices subject to FDA’s authority to regulate,” he added.
Actions Clinical Laboratory Managers Can Take
Clinical laboratory managers who want to share their thoughts about the future of LDT regulation may want to take one or both of the following actions:
Contact their representatives in Congress.
Find out whether any trade associations they belong to have taken a position on the VALID Act.
Clinical laboratory professionals should monitor the VALID Act’s progress while also paying attention to industry groups and manufacturers that support or oppose the bill.
Doing so will provide a clearer indication of who has the most to gain or lose should the legislation be passed. Pathologists and medical laboratory managers should also remain alert for further efforts by the FDA to issue proposed rulemaking to regulate LDTs.
Decision is part of UK effort to diagnose 75% of all cancers at stage I or stage II by 2028 and demonstrates to pathologists that the technology used in liquid biopsy tests is improving at a fast pace
Pathologists and medical laboratory scientists know that when it comes to liquid biopsy tests to detect cancer, there is plenty of both hope and hype. Nevertheless, following a successful pilot study at the Christie NHS Foundation Trust in Manchester, England, which ran from 2015-2021, the UK’s National Health Service (NHS) is pushing forward with the use of liquid biopsy tests for certain cancer patients, The Guardian reported.
NHS’ decision to roll out the widespread use of liquid biopsies—a screening tool used to search for cancer cells or pieces of DNA from tumor cells in a blood sample—across the UK is a hopeful sign that ongoing improvements in this diagnostic technology are reaching a point where it may be consistently reliable when used in clinical settings.
The national program provides personalized drug therapies based on the genetic markers found in the blood tests of cancer patients who have solid tumors and are otherwise out of treatment options. The liquid biopsy creates, in essence, a match-making service for patients and clinical trials.
Liquid Biopsy Genetic Testing for Cancer Patients
“The learnings from our original ‘Target’ study in Manchester were that genetic testing needs to be done on a large scale to identify rare genetic mutations and that broader access to medicines through clinical trials being undertaken across the country rather than just one site are required,” Matthew Krebs, PhD, Clinical Senior Lecturer in Experimental Cancer Medicine at the University of Manchester, told The Guardian.
Krebs, an honorary consultant in medical oncology at the Christie NHS Foundation Trust, led the Target National pilot study.
“This study will allow thousands of cancer patients in the UK to access genetic testing via a liquid biopsy. This will enable us to identify rare genetic mutations that in some patients could mean access to life-changing experimental medicines that can provide great treatment responses, where there are otherwise limited or no other treatment options available.”
Detecting cancers at earlier stages of disease—when treatment is more likely to result in improved survival—has become a strategic cancer planning priority in the UK, theBMJ noted.
“The NHS is committed to diagnosing 75% of all cancers at stage I or II by 2028, from around 50% currently,” the BMJ wrote. “Achieving such progress in less than a decade would be highly ambitious, even without disruption caused by the COVID-19 pandemic. In this context, considerable hope has been expressed that blood tests for circulating free DNA—sometimes known as liquid biopsy—could help achieve earlier detection of cancers.”
The Guardian noted that the UK’s initiative will use a liquid biopsy test made by Swiss-healthcare giant Roche.
“We can’t guarantee that we will find a fault in the genetic code of every cancer patient we recruit, or that if we do, there will be a suitable drug trial for them,” Matthew Krebs, PhD (above), lead scientist of the NHS’ Target National pilot study, told The Guardian. “However, as we learn more about the genetics of cancer in this study, it will help doctors and scientists develop new treatments to help people in the future. Ultimately, we hope liquid biopsy testing will be adopted into routine NHS care, but we need studies such as this to show the benefit of the test on a large scale and provide the evidence that patients can benefit from being matched to targeted medicines on the basis of the blood test.” (Photo copyright: Cancer Research UK Manchester Centre.)
In her article “The Promise of Liquid Biopsies for Cancer Diagnosis,” published in the American Journal of Managed Care (AJMC) Evidence-based Oncology, serial healthcare entrepreneur and faculty lecturer at Harvard Medical School Liz Kwo, MD, detailed the optimism surrounding the “revolutionary screening tool,” including its potential for:
identifying mechanisms of resistance to therapies,
measuring remaining disease after treatment,
assessing cancer relapse or resistance to treatment, and
eliminating risk surrounding traditional biopsies.
The AJMC article estimated the liquid biopsy market will be valued at $6 billion by 2030. However, Kwo also noted that clinical adoption of liquid biopsies in the US continues to face challenges.
Welch compared the investor hype surrounding liquid biopsies to that of the now-defunct blood testing company Theranos, which lured high-profile investors to pour millions into its unproven diagnostic technology.
“Effective cancer screening requires more than early detection. It also requires that starting therapy earlier helps people live to older ages than they would if they started treatment later,” he wrote. “If that doesn’t happen, liquid biopsies will only lead to people living longer with the knowledge they have a potentially incurable disease without extending their lives. These people would be subjected to cancer therapies and their toxicities earlier, but at a time when they would otherwise be experiencing no cancer-related signs or symptoms.”
And so, while there’s much excitement about the possibility of a minimally invasive way to detect cancer, anatomic pathology groups and clinical laboratories will have to wait and see if the hype and hope surrounding liquid biopsies is substantiated by further research.
The Theranos trial brought plenty of media attention, but beneath the hype, laboratory managers have lessons to ponder
Editor’s note: This is a special edition of Dark Daily brought to you by The Dark Report.
The conviction of disgraced Theranos founder and former CEO Elizabeth Holmes brings a close to one of the most infamous healthcare and high-tech trials ever.
But the high-profile case should not camouflage critical, everyday lessons for clinical laboratories.
Holmes was found guilty on Monday of four charges: three for defrauding investors and one for conspiracy to commit wire fraud (i.e., fraud perpetrated using electronic communications). The jury said she was not guilty of four other fraud charges related to patients who received blood testing, and it deadlocked on three charges related to defrauding other investors.
Look for more details about the trial’s conclusion on Monday from Dark Daily and a full analysis of what the verdict means for clinical laboratory directors and anatomical pathologists in a future issue of The Dark Report.
The trial of former Theranos CEO Elizabeth Holmes concluded this week with conviction on four charges. For clinical laboratory directors, the trial’s media hype should not obscure important lessons to be learned.
Two Lessons for Laboratories to Evaluate Following the Trial
The average lab director likely will never face the media buzz and scandalous nature of the Holmes trial. Nonetheless, laboratory leaders should take lessons from aspects of the court proceedings.
The biggest one? The director listed on a lab’s license under the Clinical Laboratory Improvement Amendments of 1988 (CLIA) holds responsibilities that have legal sway.
Such ramifications were clear during the Holmes trail given that four of Theranos’ former lab directors took the witness stand. However, it won’t take a high-profile case to bring up CLIA licenses in court. Laboratory teams should carefully review what their legal responsibilities are under the regulation.
Another important facet for lab managers to consider is adding a policy to their operations manual (if not already present) about properly dealing with whistleblower complaints.
No one will ever know if Theranos’ trajectory would have changed had executives, including Holmes, heeded the warnings of whistleblowers regarding inaccurate test data from the Edison machines. Instead, they shrugged the whistleblowers off, likely because they were young and Theranos was the subject of significant positive media coverage. The whistleblowers ended up being powerful sources of information for regulators and prosecutors.
Subscribers to The Dark Report can check out past coverage of the trial, which analyzed developments during the proceedings to explain how they should influence lab directors moving forward:
In Theranos’ Trial, CLIA Laboratory Director Has a Starring Role (Nov. 29, 2021)
CLIA Lab Director Testimony Shows Risks to Pathologists (Nov. 8, 2021)
Third CLIA Lab Director Testifies in Trial of Elizabeth Holmes (Nov. 8, 2021)
Former Theranos Lab Director Makes News at Elizabeth Holmes Trial (Oct. 18, 2021)
