Diagnosis on a chip

Next summer, a tiny bio-chip developed at UC Berkeley will help researchers in Nicaragua screen for a tropical disease that incapacitates as many as 100 million people each year.

Melding microbiology with microcircuitry, the 2 mm square ImmunoSensor provides a quick, inexpensive test for the dengue virus, commonly known as ‘break-bone fever,’ even when the nearest clinical laboratory may be hundreds of miles away.

‘In the third world, there aren’t very many specialised labs that can test these blood samples,’ says co-inventor Bernhard E. Boser, a professor in the Department of Electrical Engineering and Computer Sciences and a researcher with the Center for Information Technology Research in the Interest of Society (CITRIS). ‘Many regions don’t even have the quality of water you need to do traditional tests.’

The solution was to put the laboratory right on the chip, at a cost of less than $1 each. In fact, right now Boser and his collaborators- Molecular and Cell Biology professor P. Robert Beatty, professor Eva Harris in the School of Public Health, and their graduate students – are readying 1,000 of the ImmunoSensors to ship to Nicaragua in time for dengue season.

Spread by mosquito, the dengue virus causes brutal headaches, intense fever, rashes, and, in infants, the risk of death. The field study is being coordinated by the Sustainable Sciences Institute (SSI), a non-profit organization focused on addressing local problems related to infectious diseases in developing nations.

Currently, diseases like the dengue virus are detected with a test called the Enzyme-Linked Immunosorbent Assay (ELISA), which detects antigens and antibodies in a blood sample. Antibodies are formed by the body in response to antigens – molecules, often foreign, that the immune system recognises as threats. For every antigen, there is an antibody that binds to it. It’s this biochemical reaction that signals the immune system to start fighting off a disease. With ELISA, an enzyme is added to the sample that activates a visible coloured dye in the presence of a particular antigen or antibody.

In lieu of messy enzymes and dyes, the ImmunoSensor employs magnetism and microelectronics. First, a drop of blood is placed in a micron-scale well on the chip. There, it mixes with tiny micron-scale magnetic beads that are pre-coated with an antibody that bonds to the antigen indicative of a particular disease. ‘If the antigens are in the blood sample, the beads grab onto them,’ Boser explains.

Then, gravity causes the beads to fall onto a tiny array of 256 magnetic sensors at the bottom of the well. The sensor array is also coated with the particular antibody that binds to the disease antigen. After the beads settle, a magnetic field is applied. Beads that aren’t now immobilized by the antigen on the surface of the chip are pulled away from the sensor array.

‘We call it magnetic washing,’ Boser says.

Finally, the sensor array is activated. The electrical resistance of the array corresponds to the number of beads that are stuck on the sensors thanks to the antibody-antigen bond. The detection of immobilized beads mean the particular antigen is present and that the subject whose blood was tested most likely is infected with the dengue virus. The entire process takes little more than a minute.

Currently, the chip plugs into a conventional laptop computer running the ImmunoSensor software that provides the data to the person administering the test. The next step, Boser says, is to make the chips wireless and port the software over to a palm computing platform, even further increasing their portability.

Meanwhile, Beatty is working to develop an HIV test that would also run on the ImmunoSensor platform.

‘You could imagine buckets of these chips, all coated with different antibodies so we can not only detect on-the-spot when someone is ill, but also find out exactly what illness they have,’ Boser says.