IIT Delhi develops a novel, cheap device for sepsis diagnosis

With Spot LPS in Serum 2 (2)-Optimized
The colour of red deepens depending on the severity of sepsis

A novel, simple, low-cost device that quickly diagnoses septicaemia at bedside has been developed by an IIT Delhi researcher working along with a Consultant from Global Medical Education and Research Foundation, Hyderabad.

Septicemia (or, sepsis) is the leading cause for deaths in hospitals worldwide. According to a paper published in October 2015 in the journal Analytical Chemistry, there are about 200,000 cases of sepsis deaths each year in the U.S. alone. Sepsis is caused by the overwhelming response of the immune system to an infection. The main causative agents of sepsis are Gram-negative bacteria due to their predominance in the normal intestinal flora and the environment. Specifically, it is the endotoxin, a major constituent of the Gram-negative bacterial cell wall, that causes sepsis.

In lieu of expensive and time-consuming methods for diagnosis of sepsis, Prof. Shalini Gupta from the Department of Chemical Engineering, IIT Delhi and Dr. Venkataraman Sritharan from Hyderabad have developed a low-cost, disposable, point of care device for bedside use for sepsis diagnosis.

The device is a colorimetric rapid card test to detect endotoxin levels in human serum sample. A commonly used antibiotic colistin is combined with (conjugated) gold nanoparticles to act as a detection probe. “We used the drug to detect endotoxin as we did not want to use the antibody detection method and it also reduces the cost of testing,” said Prof. Gupta.

The principle

The drug combined with gold nanoparticles binds to the endotoxin present in serum samples. “The drug has a specific affinity to endotoxin,” she said.  Since gold particles are red in colour at the nanoscale, the drug conjugated gold nanoparticles that get bound to endotoxin appear red.  Since the amount of endotoxin present varies depending on the severity of sepsis, the amount of drug conjugated gold particles that get bound to endotoxin reveals the degree of infection; the colour of red deepens depending on the severity of sepsis.  “More the endotoixin, the more red the colour becomes because more gold nanoparticles get absorbed,” Prof. Gupta said.

To test a sample, a drop of serum is first added to the membrane on the device.  Except the endotoxin, the rest of the constituents of the blood get sucked through the membrane. The detection probe consisting of the drug conjugated gold nanoparticles is then added to the membrane. The drug binds to the endotoxin present on the membrane and turns red in colour. “It works on a concentration-dependent manner and so we get to know the degree of infection,” she said.

If the sample is from a person without sepsis, no endotoxin is present on the membrane. And since no binding of the drug to endotoxin takes place no red colour is seen on the membrane.  Since the gold nanoparticles are smaller than the pore size of the membrane, the drug conjugated gold particles pass through it in the absence of endotoxin.

The device may eliminate the need for trained scientists and a sophisticated microbiology laboratory. This is an important for India especially in rural areas where access to advanced diagnostic facilities and proper healthcare facilities is poor.

Initial validation on 80 sepsis samples has been carried out and validation using blind samples will soon be undertaken. According to her, the device may be commercially available by the end of this year. The device which took about three years to develop won the Gandhian Young Technology Innovation award in March this year.

Published in The Hindu on April 17, 2016

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2 thoughts on “IIT Delhi develops a novel, cheap device for sepsis diagnosis

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  1. I checked with Prof. Gupta and this what she had to say in response to the points raised by Mahesh Docherla:

    1. So, not yet proven clinically.

    Yes, the technology is validated only up to the prototype stage. It is yet to undergo performance testing and full clinical trials.

    2. Which endotoxin?

    Lipopolysaccharide (LPS)

    3. Maybe my mind is shot completely but I do not think the mechanism of action of Colistin is not by binding Endotoxin

    The mechanism of colistin action is by virtue of binding to the LPS in the outer cell membrane of the Gram-negative bacteria.
    http://www.medscape.com/viewarticle/772588_6

    4. Endotoxin is produced by gram negative bacteria. What about other microbial sepsis?

    Yes, the device only detects gram negative bacterial sepsis which forms about 70 per cent of the infections in India. The developers are working on the next generation platform that will delineate the gram status of infection by picking up biomarkers from gram positive bacteria. This will help narrow down the antibiotic therapy from a current broad spectrum one.

    5. The definition of sepsis is quite broad and conditions like allergic reactions, flare up of autoimmune diseases & drug reactions and certain metabolic disorders can also satisfy the current definition of sepsis. So, still to see whether this works out.

    As far as Prof. Gupta knows, the answer is no. Sepsis always includes signs of infection.

    6. Rapid card test is a failure for certain conditions such as malaria. When compared to QBC, the card test do not come positive for several days after the onset of fever and remains positive for a few months. Hence, the malaria card test cannot be used for documentation of cure and for re diagnosis if malaria recurs. I have seen several patients already who have had several malaria rapid card tests being continuously positive despite undergoing 2 or 3 courses of antimalarial treatment.

    It is not possible to comment on this in the absence of information on the particular devices that the reader talks about but it maybe so that the rapid tests are designed to measure antibodies which tend to stick around longer in the body. Our device is specially designed to circumvent these issues. It measures a pathogen associated molecular pattern that will definitely get cleared off as a result of therapy.

  2. “Initial validation on 80 sepsis samples has been carried out and validation using blind samples will soon be undertaken. According to her, the device may be commercially available by the end of this year. ” – So, not yet proven clinically. Second, which endotoxin? Third, maybe my mind is shot completely but I do not think the mechanism of action of Colistin is not by binding Endotoxin. Fourth, Endotoxin is produced by gram negative bacteria. What about other microbial sepsis? Fifth, the definition of sepsis is quite broad and conditions like allergic reactions, flare up of autoimmune diseases & drug reactions and certain metabolic disorders can also satisfy the current definition of sepsis. So, still to see whether this works out. Sixth, rapid card test is a failure for certain conditions such as malaria. When compared to QBC, the card test do not come positive for several days after the onset of fever and remains positive for a few months. Hence, the malaria card test cannot be used for documentation of cure and for re diagnosis if malaria recurs. I have seen several patients already who have had several malaria rapid card tests being continuously positive despite undergoing 2 or 3 courses of antimalarial treatment.

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