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University of Cincinnati Pathologist Develops Speedier Tissue Processing for Small Biopsies

Jul 15, 2024 | Laboratory Instruments & Laboratory Equipment, Laboratory Management and Operations, Laboratory Pathology, Laboratory Resources, Laboratory Testing

Syringe-based technique is disposable and enables clinical laboratories to process small biopsies in about two hours instead of overnight and with significantly less waste

Histotechnologists and clinical laboratory managers know that the standard method of processing tissue biopsies takes a lot of time and chemical resources and isn’t always efficient. But what if there was a way to process biopsy tissue without the need for large processors that require a large batch of tissue to be economical?

That is what cytopathologist Paul Lee, MD, PhD, Assistant Professor of Clinical Pathology, University of Cincinnati (UC) College of Medicine, asked himself when he set out to design a rapid technique for processing small biopsies.

Lee was inspired to find a way to change the process while completing his residency at the University of Massachusetts, UC News reported.

“I noticed a specific issue with the procedure for fixing and examining tissue samples to look for signs of cancer and other diseases,” Lee told UC News. “And I had this idea.”

His goal was to reduce time to answer for a patient waiting to learn if he/she has cancer.

To achieve this feat, Lee developed a new technique that, according to UC News, “employs a disposable syringe and cuvette to do individual tissue tests, using small paraffin blocks and a combined embedding-fixing process for quick, accurate reads of small biopsies.”

Lee says his technique brings the potential of “immediate reads” closer to reality.

“If that process can take just two hours, not overnight, it becomes an inpatient procedure,” Lee told UC News. “Patients don’t have to go home … and return for a surgery consult, then for surgery itself.

“All that can be arranged in a day or two,” he added. “Patient care won’t be compromised or lost to follow-up.”

Paul Lee, MD, PhD (above), Assistant Professor of Clinical Pathology at University of Cincinnati College of Medicine, compares the development of his new small-biopsy tissue processing technique for histology laboratories and clinical laboratories to the philosophy behind the invention of the Keurig single-serving beverage machine. “Let’s say you’re making a cup of coffee. If you made a whole carafe and only needed one cup, that’d be wasteful—of both time and resources. Think of this as Keurig for specimen processing.” (Photo copyright: University of Cincinnati.)

Simplifying, Accelerating Rapid Tissue Processing

Lee describes the traditional method “coupling large tissue processors with traditional embedding techniques” as “slow and wasteful.” This, he told UC News, is still how tissue processing is done.

“It [uses] huge amounts of solvent, massive paraffin blocks,” he continued, “and [leaves] doctors waiting up to seven hours for results.”

The standard procedure uses “an enormous processor, gallons of solvent, and 300-500 dehydrated specimens embedded in blocks and then cut into slices for slides,” he added.

In addition to the “waste or expense,” the process “prevents physicians from making same-day diagnoses unless they’re willing to destroy precious tissue,” Lee noted.

Lee told UC News that his technique “preserves tissue [and] doesn’t compromise the sample, so we can do ancillary tests to revalidate results … and with the disposable cuvette there’s no chance of cross-contamination. Plus, it can be easily incorporated into existing infrastructure. [It] doesn’t have to upset processes or workflow.”

Lee’s method can also save resources and reduce wait times. “I get requests [from other researchers] all the time for various samples and I have to put a lot of them off for human pathology tests,” Lee said. “They can be their own processors and not wait for results from another lab. It’s quicker for them too and uses fewer resources.”

Other Advantages of Lee’s Method 

Lee’s research team has successfully tested a prototype and they are currently awaiting a patent.

According to UC’s Office of Innovation, advantages of Lee’s new technique for small-biopsy tissue processing include:

  • Rapid, convenient processing.
  • Disposable specimen cuvette (no cross contamination).
  • Antigenicity preservation.
  • Less solvent usage (associated with less cost for solvent disposal).
  • Can be easily incorporated into existing infrastructure.
  • Very small footprint.

“Turn-around times for ‘rapid processing’ using current techniques typically range from four to seven hours, often preventing physicians from making same day diagnosis without destroying precious tissue,” the Office of Innovation noted in a statement. “This often results in delayed diagnosis, additional use of both patient and healthcare resources, and potentially poorer patient outcomes.

“Dr. Paul Lee has developed a novel tissue fixation and embedding system that combines the tissue fixation and embedding process creating a rapid processing block for biological specimens,” UC’s Office of Innovation continued. “The invention dramatically shortens processing and embedding time to approximately two hours while preserving the antigenicity and morphology of the specimen and thus allows for rapid reads of small biopsies in a timeframe that was not previously achievable.”

Lee’s work could streamline tissue processing in histology laboratories and increase efficiency without sacrificing accuracy. Anatomic pathologists and clinical laboratories would be wise to monitor this revolutionary new technology for further developments.

—Ashley Croce

Related Information:

UC Pathologist Designs Rapid Technique For Small Biopsies

Syringe Based Rapid Processor for Small Biopsies

New Research Challenges Long-Held Theory about Causes of Alzheimer’s Disease, Creating the Possibility of Useful New Biomarkers for Clinical Laboratory Tests

Dec 7, 2022 | Digital Pathology, International Laboratory News, Laboratory Pathology, Laboratory Resources, Laboratory Testing, Precision Medicine

University of Cincinnati researchers hypothesize that low levels of amyloid-beta protein, not amyloid plaques, are to blame

New research from the University of Cincinnati (UC) and Karolinska Institute in Sweden challenges the prevailing theory about the causes of Alzheimer’s disease, suggesting the possibility of new avenues for the development of effective clinical laboratory assays, as well as effective therapies for treating patients diagnosed with Alzheimer’s.

Scientists have long theorized that the disease is caused by a buildup of amyloid plaques in the brain. These plaques are hardened forms of the amyloid-beta protein, according to a UC news story.

However, in their findings published in the Journal of Alzheimer’s Disease, titled “High Soluble Amyloid-β42 Predicts Normal Cognition in Amyloid-Positive Individuals with Alzheimer’s Disease-Causing Mutations,” the researchers advanced an alternative hypothesis—that Alzheimer’s is instead caused by “depletion” of a soluble form of that same amyloid-beta protein.

“The paradox is that so many of us accrue plaques in our brains as we age, and yet so few of us with plaques go on to develop dementia,” said Alberto Espay, MD, one of the lead researchers of the study, in another UC news story. Espay is Professor of Neurology at the UC College of Medicine and Director and Endowed Chair of the Gardner Center for Parkinson’s Disease and Movement Disorders.

“Yet the plaques remain the center of our attention as it relates to biomarker development and therapeutic strategies,” he added.

Alberto Espay, MD

“It’s only too logical, if you are detached from the biases that we’ve created for too long, that a neurodegenerative process is caused by something we lose, amyloid-beta, rather than something we gain, amyloid plaques,” said Alberto Espay, MD (above), in a University of Cincinnati news story. “Degeneration is a process of loss, and what we lose turns out to be much more important.” The UC study could lead to new clinical laboratory diagnostics, as well as treatments for Alzheimer’s and Parkinson’s diseases. (Photo copyright: University of Cincinnati.)

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High Levels of Aβ42 Associated with Lower Dementia Risk

In their retrospective longitudinal study, the UC researchers looked at clinical assessments of individuals participating in the Dominantly Inherited Alzheimer Network (DIAN) cohort study. DIAN is an ongoing effort, sponsored by the Washington University School of Medicine in St. Louis, to identify biomarkers associated with Alzheimer’s among people who carry Alzheimer’s mutations.

The researchers found that study participants with high levels of a soluble amyloid-beta protein, Aβ42, were less likely to develop dementia than those with lower levels of the protein, regardless of the levels of amyloid plaques in their brains or the amount of tau protein—either as phosphorylated tau (p-tau) or total tau (t-tau)—in their cerebral spinal fluid. P-tau and t-tau are proteins that form “tau tangles” in the brain that are also associated with Alzheimer’s.

One limitation of the study was that the researchers were unable to include Aβ40, another amyloid-beta protein, in their analysis. But they noted that this “did not limit the testing of our hypothesis since Aβ40 exhibits lower fibrillogenicity and lesser depletion than Aβ42, and is therefore less relevant to the process of protein aggregation than Aβ42.” Fibrillogenicity, in this context, refers to the process by which the amyloid-beta protein hardens into plaque.

While the presence of plaques may be correlated with Alzheimer’s, “Espay and his colleagues hypothesized that plaques are simply a consequence of the levels of soluble amyloid-beta in the brain decreasing,” UC news stated. “These levels decrease because the normal protein, under situations of biological, metabolic, or infectious stress, transform into the abnormal amyloid plaques.”

The UC News story also noted that many attempts to develop therapeutics for Alzheimer’s have focused on reducing amyloid plaques, but “in some clinical trials that reduced the levels of soluble amyloid-beta, patients showed worsening in clinical outcomes.”

New Therapeutics for Multiple Neurodegenerative Diseases

Eisai, a Japanese pharmaceutical company, recently announced phase three clinical trial results of lecanemab, an experimental drug jointly developed by Eisai and Biogen, claiming that the experimental Alzheimer’s drug modestly reduced cognitive decline in early-stage patients, according to NBC News.

Espay noted that lecanemab “does something that most other anti-amyloid treatments don’t do in addition to reducing amyloid: it increases the levels of the soluble amyloid-beta.” That may slow the process of soluble proteins hardening into plaques.

Beyond their findings about Alzheimer’s, the researchers believe similar mechanisms could be at work in other neurodegenerative diseases such as Parkinson’s disease, where the soluble alpha-synuclein protein also hardens into deposits.

“We’re advocating that what may be more meaningful across all degenerative diseases is the loss of normal proteins rather than the measurable fraction of abnormal proteins,” Espay said. “The net effect is a loss not a gain of proteins as the brain continues to shrink as these diseases progress.”

Espay foresees two approaches to treating these diseases: Rescue medicine, perhaps based on increasing levels of important proteins, and precision medicine, which “entails going deeper to understand what is causing levels of soluble amyloid-beta to decrease in the first place, whether it is a virus, a toxin, a nanoparticle, or a biological or genetic process,” according to UC News. “If the root cause is addressed, the levels of the protein wouldn’t need to be boosted because there would be no transformation from soluble, normal proteins to amyloid plaques.”

Clinical Laboratory Impact

What does this mean for clinical laboratories engaged in treatment of both Alzheimer’s and Parkinson’s patients? A new understanding of the disease would create “the opportunity to identify new biomarkers and create new clinical laboratory tests that may help diagnose Alzheimer’s earlier in the disease progression, along with tests that help with the patient’s prognosis and monitoring his or her progression,” said Robert Michel, Editor-in-Chief of Dark Daily and its sister publication The Dark Report.

Given the incidence of Alzheimer’s disease in the population, any clinical laboratory test cleared by the FDA would be a frequently-ordered assay, Michel noted. It also would create the opportunity for pathologists and clinical laboratories to provide valuable interpretation about the test results to the ordering physicians.

—Stephen Beale

Related Information:

High Soluble Amyloid-β42 Predicts Normal Cognition in Amyloid-Positive Individuals with Alzheimer’s Disease-Causing Mutations

UC Study: Decreased Proteins, Not Amyloid Plaques, Tied to Alzheimer’s Disease

US News: Scientists Propose New Mechanism Driving Alzheimer’s

Scientists Propose New Mechanism Driving Alzheimer’s Disease

Alzheimer’s: Lack of Beta-Amyloid, Not Plaque Buildup, May Be the Culprit

Better Cognitive Predictor in People at High Risk of Alzheimer’s Disease

UC Study: Researchers Question Prevailing Alzheimer’s Theory with New Discovery

ABPP Amyloid Plaques’ Role in Onset of Alzheimer’s Questioned by Cincinnati University: GlobalData Reveals That ABPP Targeted by a Tenth of All Alzheimer’s Drugs

Blots on a Field? A Neuroscience Image Sleuth Finds Signs of Fabrication in Scores of Alzheimer’s Articles, Threatening a Reigning Theory of the Disease

WVXU: Does a Key Alzheimer’s Study Contain Fabricated Images?

Researchers at the Stanford University School of Medicine Develop Cutting-Edge Test to Identify Whether an Infection is Bacterial or Viral

Oct 24, 2016 | Coding, Billing, and Collections, Digital Pathology, Instruments & Equipment, Laboratory Hiring & Human Resources, Laboratory Instruments & Laboratory Equipment, Laboratory Management and Operations, Laboratory News, Laboratory Operations, Laboratory Pathology, Laboratory Testing

Early results are promising and this technology could lead to a clinical laboratory test that would give microbiologists and pathologists a new tool for helping diagnose infections

Infectious disease physicians and clinical laboratory scientists will be interested to learn that researchers at the Stanford University School of Medicine recently developed a new blood test that can identify whether the source of an infection is bacterial or viral.

These findings were published in Science Translational Medicine in July. The paper was authored by Stanford staff members Timothy Sweeney, MD, PhD, and Purvesh Khatri, PhD, Assistant Professor (Research) of Medicine (Biomedical Informatics Research-ITI Institute) and of Biomedical Data Science. Hector Wong, MD, of the University of Cincinnati was the third co-author of the study.

These findings are timely because, starting on January 1, 2017, hospitals and health systems will need to implement more rigorous antimicrobial stewardship programs to comply with new requirements of the Centers for Medicare & Medicaid Services (CMS) and The Joint Commission (TJC). A clinical laboratory test that makes it easier to determine whether the cause of an infection is bacterial or viral would be a welcome tool for physicians, pharmacists, pathologists, and microbiologists involved in a hospital’s infection control program. (more…)

Cheap, Disposable Biometric Patch to Monitor Stress and Fatigue in Military Personnel May Be Adapted to Monitor Biomarkers Used by Clinical Pathology Laboratories

Dec 10, 2014 | Laboratory Instruments & Laboratory Equipment, Laboratory News, Laboratory Operations, Laboratory Pathology

The U.S. Air Force Research Laboratory tapped nanotechnology experts at the University of Massachusetts Amherst to develop a patch that targets stress biomarkers in sweat

One potential disruptor of medical laboratory testing, as it exists today, are wearable biometric devices. These are already popular with athletes and health-conscious people. To meet this demand, a continual stream of innovative biometric gear is hitting the marketplace.

Foremost among the consumers for this technology is the U.S. military. Military leaders recognize the importance of monitoring the physical condition and health of armed forces personnel in the field. Wearable biometric devices are a perfect solution to meet this need. (more…)

Cincinnati’s Health Alliance Dissolves, Was a Pioneer in Consolidation of Clinical Pathology Laboratory Testing

Sep 20, 2010 | Laboratory News, Laboratory Pathology

Its Laboratory Alliance Lab Outreach Business was Sold in 2003

Back in the mid-1990s, Cincinnati was the location for a multi-hospital clinical laboratory consolidation that was one of the first and biggest of its time. Now, all but one of the original organizing hospitals of The Health Alliance of Greater Cincinnati have gone their separate ways.

The original goal was for the alliance to help its not-for-profit health members compete economically. Now this story may turn out to be a cautionary tale about the perils of alliances where health entities share operations but not governance.

Back in 2003, financial struggles of The Health Alliance contributed to its decision to sell ownership of the outreach business of Alliance Laboratory Services, the consolidated clinical laboratory organization, to LabOne, Inc. LabOne’s ownership of this medical laboratory later passed to Quest Diagnostics, Incorporated (NYSE: DGX) when LabOne was itself acquired by Quest Diagnostics in 2005. (See The Dark Report, August 22, 2005, “Quest Pays $934 Million In Acquisition of LabOne.”)

(more…)

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