THE much-vaunted 鈥渓aboratory-on-a-chip鈥� took another step forward this week
as a Californian company revealed that it had developed a penny-sized microchip
that extracts bacteria from blood samples using just a zap of electricity.
Current laboratory tests take days to identify the bacterium causing an
infection. In an effort to speed things up, biotechnologists have been
developing the lab-on-a-chip concept so that smart slivers of silicon can
analyse blood or saliva in just a few minutes
(鈥淒evilish tricks with tiny
chips鈥�, 快猫短视频, 1 March 1997, p 22).
A major sticking point has been how to isolate pathogens, often present only
in very low numbers, from the millions of human cells in a blood sample. Now
Jing Cheng and his colleagues at the biotechnology company Nanogen in San Diego
have successfully tested a square-centimetre array of electrodes that can be
programmed to attract only the cells researchers want, rapidly separating them
from the blood. 鈥淚t鈥檚 very quick,鈥� says Cheng. 鈥淚t takes minutes.鈥�
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The array of electrodes produces a high-frequency alternating current in a
blood sample. In such a field, a given cell will become either positively or
negatively charged, depending on its electrical properties. By trial and error,
Cheng worked out a frequency that gave the bacteria a negative electrical
charge, but left a positive charge on the human cells.
After zapping a sample of blood spiked with Escherichia coli, Cheng
switched the array to direct current. The bacteria stuck to the now positive
electrodes like iron filings to a magnet, while the blood cells were
repelled.
Cheng then ruptured the bacteria with a 400-volt shock. 鈥淚t basically
short-circuits the cell membrane and breaks out the DNA and RNA,鈥� he says. After
washing away the cell membranes and proteins, he analysed the purified genetic
material on a second electronic chip for the presence of bacterial DNA. The
entire procedure, described in the current issue of Nature
Biotechnology (vol 16, p 541), took just 30 minutes.
So far, Cheng has separated four types of bacteria from blood, including
Streptococcus and Staphylococcus. The chip has also singled out
cultured carcinoma cells, raising the possibility that the technique could be
useful in diagnosing cancer.
In theory, the array can grab any type of cell, once its behaviour in
electric fields is known. Cheng says that鈥檚 a major advance over earlier
鈥減assive鈥� cell-sorting techniques, such as filtration. 鈥淲ith a filter, you can
get only large cells,鈥� he says. 鈥淲e can pull out cells independent of their
蝉颈锄别.鈥�
The array is an important step toward creating labs-on-a-chip, according to
Peter Wilding, a clinical chemist who works on such devices at the University of
Pennsylvania in Philadelphia. 鈥淭o say that this is just another incidental
development in nanotechnology would be quite wrong.鈥�
Cheng is now developing more compact arrays that contain 10 000 electrodes.
That, together with improvements in the washing reagents, should speed up the
process even further. 鈥淲e hope that by early next year we鈥檒l have it down to 15
minutes or less,鈥� he says.
Another company, Orchid Biocomputer of Princeton, New Jersey, is working on a
different kind of lab-on-a-chip. Its 鈥淐hemtel鈥� chip contains 144 chambers, each
capable of sustaining a different chemical reaction鈥攈opefully speeding the
hunt for new drugs.