Lab-on-a-chip technology could reduce the time needed to identify infection-causing bacteria and for physicians to prescribe correct antibiotics 

Pathology groups and medical laboratories may see their role in the patient-care process grow if researchers succeed in developing culture-independent diagnostic tools that quickly identify bacterial infections as well as pinpoint the antibiotics needed to treat them.

In the battle against antibiotic-resistant infections (AKA “super bugs”) the National Institutes of Health (NIH) is funding nine research projects aimed at thwarting the growing problem of life-threatening infections that no longer are controlled or killed by today’s arsenal of drugs.

Common Practices in Hospitals Leading to Super Bugs

Currently, when infections are suspected in hospitals or other settings where illness can quickly spread, samples are sent to a central medical laboratory where it may take up to three days to determine what germ is causing the infection. Because of that delay, physicians often prescribe broad-spectrum antibiotics based on a patient’s symptoms rather than lab test results, a practice that can lead to the growth of antibiotic-resistant microbes.

“Antimicrobial resistance is a serious global health threat that is undermining our ability to effectively detect, treat, and prevent infections,” said National Institute of Allergy and Infectious Diseases (NIAID) Director Anthony S. Fauci, MD, in a news release. “One way we can combat drug resistance is by developing enhanced diagnostic tests that rapidly identify the bacteria causing an infection and their susceptibility to various antimicrobials. This will help physicians determine the most effective treatments for infected individuals and thereby reduce the use of broad-spectrum antibiotics that can contribute to the drug resistance problem.”

The Centers for Disease Control and Prevention (CDC) estimates that preventing infections and improving antibiotic prescribing could save 37,000 lives from drug-resistant infections over five years.

As Director of the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), Anthony S. Fauci, MD, (above) leads research to prevent, diagnose, and treat infectious diseases, such as HIV/AIDS, influenza, tuberculosis, malaria, and illness from potential agents of bioterrorism. He serves as one of the key advisors to the White House and U.S. Department of Health and Human Services (HHS) on global AIDS issues. (Photo and caption copyright: NIH Medline Plus.)

As Director of the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), Anthony S. Fauci, MD, (above) leads research to prevent, diagnose, and treat infectious diseases, such as HIV/AIDS, influenza, tuberculosis, malaria, and illness from potential agents of bioterrorism. He serves as one of the key advisors to the White House and U.S. Department of Health and Human Services (HHS) on global AIDS issues. (Photo and caption copyright: NIH Medline Plus.)

NIH Funding Research into Diagnostic Tools That Identify Antibiotic Susceptibility

NIAID, which is part of the NIH, is awarding more than $11 million in first-year funding to three companies and six academic institutions:

BioFire Diagnostics of Salt Lake City, Utah, Project name: FilmArray Direct: Rapid Diagnosis of Antimicrobial-Resistant Pathogens from Blood;

Brigham Young University of Provo, Utah, Project name: Multiplexed, Non-Amplified, Nucleic Acid-Based Identification of Multidrug Resistant Pathogens Using an Integrated Optofluidic Platform;

Denver Health and Hospital Authority, Project name: Ultrarapid Culture-Independent Detection of High-Priority Carbapenem Resistant Enterobacteriaceae Directly from Blood;
First Light Biosciences of Bedford, Mass., Project name: Rapid Detection of Pathogens and Antimicrobial Susceptibility Directly in Patient Samples

GeneFluidics of Irwindale, Calif., Project name: A Fully Integrated CentriFluidic System for Direct Bloodstream Infection PID/AST;

Johns Hopkins University of Baltimore, Maryland, Project name: A Droplet-Based Single Cell Platform for Pathogen Identification and AST ;

Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Mass., Project name: RNA-Based Diagnostics for Rapid Pathogen Identification and Drug Resistance;

University of California, Berkeley, Project Name: Consortium for Drug-Resistant Gram-Negative Pathogen Detection; and,

University of California, Irvine, Project name: Integrated Comprehensive Droplet Digital Detection (IC 3D) System for Rapid Detection of Bacteria and Antimicrobial Resistance.

Each of the institutions receiving an NIAID award will develop a diagnostic tool that identifies and provides corresponding antibiotic susceptibility information for one or more of the following bacteria:

Klebsiella pneumonia;
Acinetobacter baumannii;
Pseudomonas aeruginosa;
Enterobacter species; and,
Escherichia coli.

To be eligible for the funding, each academic institution had to team up with a corporate partner with demonstrated experience in product development.

Lab-on-a-Chip Device Can Detect UTIs in Three Hours Rather than Three Days

Johns Hopkins is leading a multi-institution team that is building a palm-size lab-on-a-chip (LOC) device that will detect the bacterial linked to urinary track infections (UTIs). IHS Engineering360 credits Engineering Professor Jeff Tza-Huei Wang, PhD, with designing an LOC that “automates the complex, multistep polymerase chain reaction tests that labs now perform to detect infectious diseases.”

Wang’s dual-module microfluidic device “uses manipulation of microfluidic droplets to process a culture and identify the specific strain of bacteria that is causing the infection,” while a second module—still under development—will determine the antibiotic needed as well as the correct dose needed to combat the specific infection, according to an IHS Engineering360 feature.

“We believe our microfluidic device will give the appropriate answers within three hours, rather than two or three days under the present system of analyzing cultures in a centralized lab,” Wang told IHS Engineering360.

In its news release, Johns Hopkins University quoted Wang as saying the technology under development should be useful in identifying and treating other infections as well such as sexually transmitted diseases.

Wang is partnering in the project with co-principal investigator Joseph C. Liao, MD, a Stanford University urologist who will validate that the technology works on bacteria associated with urinary tract infections, and with researchers from the University of Arizona, who will assist in developing the second module. GE Global Research will provide advice on the future commercialization of the device.

Wang believes microfluidic LOC devices can play an important role in slowing the growth of antibiotic-resistant infectious diseases. The CDC estimates that each year at least 2 million people become infected with bacteria that are resistant to antibiotics and as many as 23,000 people die as a direct result of these infections.

“If this trend continues, we are at risk of going back almost a century to a time before the first antibiotics were introduced,” Wang said in the Johns Hopkins statement.

Glowing Bacteria DNA Will Lead Doctors to Proper Antibiotic Treatment

The Deseret News reported that Brigham Young University (BYU) researchers are attempting to develop a hand-held device that could capture bacteria from blood samples and attach molecules to the bacteria’s DNA, causing it to glow when illuminated by laser. Based on the fluorescent signal given off, doctors would be able to identify the bacteria and the proper antibiotic treatment.

“We tend to want to put everything onto a chip, so that’s what I will try to do,” said BYU Electrical and Computer Engineering Professor Aaron Hawkins, PhD, the lead investigator on the project, told the newspaper. “My graduate students will build structures on the silicon that try to mimic what we would do in a larger lab in smaller volumes.”

BYU’s corporate partner is Salt Lake City-based biomedical company Great Basin Scientific.

Pathologists and Clinical Labs Will Become Part of the Diagnostic Process

Funding for these projects extend to 2020, so none of the devices will be commercially available in the near future. Nonetheless, this research shows the value clinical laboratories can provide to the patient-care process and may provide pharmacists with a reason to work more closely with pathologists and clinical chemists if a single test can quickly identify both the bacteria causing a patient’s infection and the right antibiotic to treat it.

—Andrea Downing Peck

Related Information:

Tiny Lab Devices Could Attack Huge Problem of Drug-Resistant Infections

Lab on Chip Revolution Find the Right Niche

BYU Researchers Fighting Back Against Super Bugs

NIH Funds Nine Antimicrobial Resistance Diagnostics Projects

A Fully Integrated Centrifluidic System for Direct Bloodstream Infection PID/AST

Unexpected Discovery of Source of Lethal, Antibiotic-Resistant Strain of E. Coli Could Lead to New Medical Laboratory Tests and Preventative Treatment

New Tool for Fighting Antibiotic-Resistant Bacteria: Meet Bacteriophage

Researchers at Auburn University Collaborate with Clinical Laboratory Team at Keesler Air Force Base to Detect Antibiotic-resistant Bacteria in Just 10 Minutes

First-generation of a Clinical Laboratory-on-a-Chip Measures Multiple Bio-markers and Also Drugs in The Body

Nanotechnology-Based Medical Laboratory Test Chip Developed at Stanford University Detects Type-1 Diabetes in Minutes and Can Be Used in Doctors’ Offices