Biochip Device Tests Malaria Drug Efficacy, Safety

Malaria model chip device (Hesperos Inc.)

5 July 2023. A lab-on-a-chip device with human organ cells is shown in lab tests to distinguish between malaria strains and detect drug toxicity when assessing blood for seven days. A team from the company developing the device, Hesperos Inc. in Orlando, Florida, reports results of the tests in the 28 June 2023 issue of the journal Scientific Reports.

Hesperos Inc. creates models of human organs as small microfluidic or lab-on-a-chip devices for preclinical assessments of new drugs. The eight year-old company seeks to provide alternatives to animal testing commonly used to test new drugs before human clinical trials. While lab animals may share much of the same genome as humans, says Hesperos, they can still return unreliable results, and also raise ethical issues of animal cruelty. The company was founded by biomedical engineering professors Michael Shuler and James Hickman, at Cornell University and University of Central Florida respectively, with Shuler serving as Hesperos’s president and Hickman as chief scientist.

The Hesperos technology builds models of functioning human organs with fine laser-cut channels and wells engraved into acrylic plastic, lined with live human tissue and cells. Chips representing different organs can be linked together to model multiple-organ activity in the body, or as in this case, build multiple organ functions into a single chip. The devices are designed to illustrate direct effects of experimental drugs on human tissue and cells, but also later effects of new compounds after they’re metabolized. In June 2019, Science & Enterprise reported on a multi-chamber biochip device built by Hesperos to test experimental cancer drugs, assessed in the journal Science Translational Medicine.

Infections tested from two parasite strains

In the new paper, a Hesperos team led by Hickman evaluated a biochip device for testing malaria treatments, modeling infections by the Plasmodium falciparum or P. falciparum parasite, spread by mosquitoes, that cause malaria. The chip represents functions of the liver, spleen, and endothelial tissue that lines blood vessels in the body, built with three chambers, one for each organ or tissue type, and precursor cells cultured into mature tissue in the chambers. In addition, red blood precursor cells circulate through the model for seven days. Hesperos collaborated with the Medicines for Malaria Venture on the project, with funding from the Bill and Melinda Gates Foundation.

The researchers tested the malaria model chip with infections from two strains of P. falciparum parasite, one strain sensitive to chloroquine, a common drug for preventing and treating malaria, and a chloroquine-resistant strain. For each type of infection, the team sent chloroquine into the chip at three dosage levels. Results show tissue models in the biochip responded strongly to chloroquine when infected with the sensitive P. falciparum strain, but only moderately responsive to the drug when infected with the resistant strain, similar to human infections. The findings also show evidence of toxic effects of chloroquine, higher incidence of ruptured red blood cells circulating through the chip, at higher doses of the drug.

“The work described here,” say the authors, “establishes a new approach to the evaluation of anti-malarial therapeutics in a realistic human model with recirculating blood cells for seven days.” And the researchers conclude, “While further development is still necessary, we believe that this creates a precedent for future progress in the field of malaria research.”

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