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Clinical Laboratories and Pathology Groups

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Clinical Laboratories and Pathology Groups

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Zhejiang University Researchers Develop Ultrasensitive Nanoscale Sensor That Detects Lung Cancer in Breath Samples

Research could lead to new biomarkers for clinical laboratory tests that spot disease early in patients

As we have covered in previous Dark Daily ebriefs, there are ongoing efforts to develop diagnostic assays that use human breath as the specimen. One early example was the breath specimen for Helicobacter pylori (H. pylori) testing—the bacteria that causes peptic ulcers—in the 1990s. Thus, a new sensor developed by scientists at Zhejiang University in China that can detect the presence of lung cancer in human breath will be of interest to medical laboratory scientists and clinical laboratories working on such testing.

In a proof-of-concept study, the Zhejiang University researchers “developed ultrasensitive nanoscale sensors that in small-scale tests distinguished a key change in the chemistry of the breath of people with lung cancer,” according to an American Chemical Society (ACS) news release.

The new research exemplifies how instruments are becoming increasingly sensitive to detection of smaller specimen quantities, making it possible to even use exhaled breath to diagnose lung cancer, noted a review article published in Science Direct.

The scientists published their findings in ACS Sensors titled, “Ultrasensitive In203-based Nanoflakes for Lung Cancer Diagnosis and the Sensing Mechanism Investigated by Operando Spectroscopy.”

“This study presents a novel Pt@InNiOx [platinum (Pt), indium (In), nickel (Ni)] nanoflake isoprene sensor that achieves an exceptionally low limit of detection at two parts per billion (2ppb)—the lowest reported for isoprene sensor to date,” wrote study lead author, Pingwei Liu, PhD (above), distinguished research fellow, Zhejiang University, et al, in ACS Sensors. “Our work not only provides a breakthrough in low-cost, noninvasive cancer screening through breath analysis but also advances the rational design of cutting-edge gas sensing materials.” Clinical laboratories working with breath sample biomarkers will be intrigued by this new advancement in the technology. (Photo copyright: Zhejiang University.)

Finding the Breakthrough Sensor

The Zhejiang University researchers were motivated by the potential for rapid gas sensing in diagnostics. Many gases, including carbon dioxide, are exhaled. But one particular gas, isoprene, they found “can indicate the presence of lung cancer,” the news release states.  

However, while breath is readily available, it is not easy to isolate breath biomarkers. That is because a detector needs to “differentiate between volatile chemicals, withstand the natural humidity of exhaled breath, and detect tiny quantities of specific chemicals,” New Atlas explained.

To detect small specimen quantities of isoprene, a highly sensitive sensor needed to be developed—one that would be a step up from standard indium oxide-based breath sensors.

The scientists experimented with a series of indium (III) oxide (In203)-based nanoflake sensors until they found the sensor that performed consistently in nine experiments. They called it Pt@InNiOx for the platinum (Pt), indium (In), and nickel (Ni) it contained.

According to the news release, the Pt@InNiOx sensor:

  • Had “sensitivity that far surpassed earlier sensors” as evidenced by detection of isoprene as low as 2ppb.
  • Emphasized isoprene attraction over other volatile compounds in breath.
  • Has advanced sensitivity due to “Pt nanoclusters uniformly anchored on the nanoflakes” activating the isoprene sensing.

Gadget Review described the innovation as a “significant advance in diagnostic capability” that uses nanoscale technology along with “indium oxide nanoflakes with platinum-based nanoclusters.”  

Developing the Lung Cancer Diagnostic Device

The scientists put their Pt@InNiOx nanoflakes into a portable sensing device for breath analysis. They then inserted breath samples from 13 people including five who had lung cancer. They found that:

  • In samples from people with cancer, the device enabled detection of isoprene levels lower than 40 ppb.
  • In samples from cancer-free participants, the device found isoprene levels more than 60 ppb.

“We integrate these ultrasensitive Pt@InNiOx nanoflakes into a miniaturized portable electronic device that successfully distinguishes lung cancer patients with expiratory isoprene below 40ppb, from the healthy population with isoprene above 60 ppb, enabling an accurate diagnosis in clinics,” wrote study lead author, Pingwei Liu, PhD, distinguished research fellow, Zhejiang University, et al, in ACS Sensors.

“As the isoprene hits the nanoflakes, electron release is sparked in a way that can be measured,” MSN Health reported, adding that the nanoflakes were also able to find isoprene in other chemicals and operate even in humid conditions.

Breath as Lab Test Biomarker for Cancer

In the United States, more people die from lung cancer than any other form of cancer, according to US Centers for Disease Control and Prevention statistics. The CDC data show there were 209,500 new lung and bronchus cancer cases in 2022, the most recent year for available data.

The Zhejiang University scientists reportedly plan to continue their research on the sensing materials and link between isoprene and lung cancer.

Studies continue to show many components in human breath can be used as clinical laboratory test biomarkers. Assays that use the breath as specimen may one day play an important role in early diagnosis of lung cancer and other diseases. 

                        —Donna Marie Pocius

Related Information:

Detecting Evidence of Lung Cancer in Exhaled Breath

Ultrasensitive In203-based Nanoflakes for Lung Cancer Diagnosis and the Sensing Mechanism Investigated by Operando Spectroscopy

Advanced Sensing Tech Can Detect Lung Cancer in Your Exhaled Breath

Scientists Develop Breakthrough Breath Test for Early Lung Cancer Detection

Signs of Lung Cancer Can Now Be Detected When You Exhale

NASA Creates Breath Analyzer to Measure Multiple Biomarkers in Space

Breath Sample Is Used by Opteev Technologies’ Combined COVID/Influenza/RSV Screening Device with 95% Sensitivity and 90% Specificity

German Researchers Create Non-invasive Lab-on-a-Chip Biosensor That Detects Antibiotic Levels from Breath Samples

NIST Scientists Enhance Frequency Comb Breathalyzer Enabling It to Detect Multiple Disease Biomarkers

Despite Passage of New Law on CLIA enforcement, Ohio State University Settles with CMS Agrees to Pay $268,000, and Names New Clinical Laboratory Medical Director

Medical laboratory continues to operate, retains its CLIA certificate, and maintains that the PT violations at heart of CMS case were inadvertent

One nationally prominent clinical laboratory organization closed its chapter in the ongoing story of CLIA enforcement of the regulations governing the inadvertent referral of proficiency testing specimens. But this chapter ended with an unexpected twist for the Ohio State University Wexner Medical Center (OSUWMC), which was given severe sanctions by officials of the Centers for Medicare & Medicaid Services (CMS), despite recent enactment of a new federal law on the subject of enforcement of CLIA proficiency testing errors.

The settlement between OSUWMC and CMS was announced on January 16. It calls for OSUWMC to:

  • Appoint a new medical director for the clinical laboratory,
  • Pay $268,000, and
  • Provide additional training to the medical laboratory staff in proficiency testing (PT).

New Medical Director Named at OSUWMC’s Clinical Laboratory

OSU named Daniel Sedmak, M.D., to the position of medical director of the clinical laboratory, as part of this resolution with federal officials who administer the Clinical Laboratory Improvement Amendments (CLIA). Sedmak is currently the Chair of the OSU College of Medicine, Department of Pathology and a professor of pathology.

Ohio-state-medical-center-photo

Last month, Ohio State University Wexner Medical Center issued a press release stating that it had resolved pending sanctions assessed against its clinical laboratory by the Centers for Medicare & Medicaid Services for violations of CLIA requirements, including the inadvertent referral of proficiency testing specimens. (Photo by Wikipedia.com.)

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TEST Act Signed By President Obama, Provides Regulators Discretion When Clinical Laboratories Mistakenly Violate CLIA PT Requirements

Pathologists will welcome this law, which provides more latitude for federal regulators should a medical laboratory inadvertently refer a proficiency testing specimen

Last Tuesday, the clinical laboratory testing industry gained an important measure of regulatory relief after President Obama signed into law the Taking Essential Steps for Testing (TEST) Act of 2012. This law removes severe penalties for medical laboratories that inadvertently violate proficiency testing (PT)  requirements.

More specifically, the language of the TEST Act provides guidance to federal regulators to resolve an issue concerning the inadvertent referral of PT specimens as defined by the Clinical Laboratory Improvement Amendments (CLIA) statute of 1988. (See The Dark ReportCongress May Respond to Tough CLIA PT Penalties,” August 6, 2012.) (more…)

Bill to Fix CLIA Proficiency Testing Language for Clinical Laboratories Passes in the House, Awaits Senate’s Return in November

New law would lessen penalties for medical laboratories from violations of CLIA regulations if they made inadvertent referrals of  proficiency tests to other clinical labs

Clinical laboratories may have to wait at least another month before the U.S. Senate returns from recess to vote on a bill to remove severe penalties for labs that inadvertently violate certain CLIA proficiency testing (PT) requirements. A similar bill was passed in the House in September.

The bill, S. 3391: Taking Essential Steps for Testing Act, was ready for a Senate vote in mid-October. It was set aside so that senators could return home while the campaign season entered its final weeks. (more…)

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