The children of the future may be conceived and spend their first few days of development on a computer-controlled chip.
In a move recalling Aldous Huxley鈥檚 famous production lines for making babies in Brave New World, researchers in the US are building a 鈥渃hip鈥� that can automatically carry out all the steps involved in IVF, from fertilising eggs to preparing embryos for implantation.
Ultimately, such devices 鈥� which amount to artificial reproductive tracts 鈥� may even be able to sort and test embryos for genetic flaws.
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So far researchers David Beebe and Matthew Wheeler have built prototypes that can carry out the major steps involved in IVF, though not all on the same chip. Far more mouse embryos develop successfully on these devices than by traditional methods.
The researchers say they expect the technology will first be used for livestock production, but their eventual aim is to use it for human embryos. The work could be the first step towards a future in which IVF becomes the norm, says George Seidel, a reproductive physiologist at Colorado State University in Fort Collins.
鈥淔ifty or 100 years from now, our in vitro procedures for parts or even all of pregnancy may end up being safer than dealing with the various things that occur in the body 鈥� in terms of viruses that the mother comes across, toxins, and so on.鈥�
Dumped in a dish
In conventional IVF, sperm and eggs are dumped into a Petri dish where the fertilised eggs grow until they鈥檙e ready to be implanted. As embryos need different culture media at different stages, embryologists transfer them from one dish to another via a pipette.
鈥淚t鈥檚 like being plucked out of the Atlantic Ocean and stuck into the Pacific Ocean,鈥� says Beebe, a biomedical engineer at the University of Wisconsin, Madison.
So Beebe and Wheeler, an embryologist at the University of Illinois at Urbana-Champaign, designed a device to mimic conditions inside a female鈥檚 reproductive tract.
The device, made of a transparent elastomer, resembles a small glass slide and contains a network of tiny channels, each around 0.2 millimetres in depth and width. The researchers connect the channels to programmable syringe pumps, which can move embryos around and add or remove fluids.
Acid test
To test the device, the team cultured mouse embryos to see how many developed to the 鈥渂lastocyst鈥� stage, ready to be implanted.
鈥淚n 48 hours, in the traditional Petri dish, none of them made it to the blastocyst stage. In our channels, about 75 per cent made it,鈥� says Beebe. 鈥淭he embryos were transplanted into hosts and live pups were born. So there doesn鈥檛 appear to be any detrimental effect.鈥�
The researchers also used the device to remove the 鈥渮ona pellucida鈥� shell that encases early embryos. In human IVF, this 鈥渁ssisted hatching鈥� can be used to encourage implantation. Traditionally, the embryo is put into an acid medium and quickly removed when the embryologist sees the zona break up.
But waiting this long may damage the embryos. By washing acid over mouse embryos 鈥減arked鈥� in a microchannel on a chip (see Graphic), the team found even with a brief exposure, the zona broke up after the acid was removed. 鈥淧eople have been leaving embryos in the acid too long,鈥� says Beebe.
Embryo weeding
In a separate experiment, the team matured mouse eggs inside the channels, then fertilised them by squirting sperm over them. Eventually they hope to integrate all the steps into a single artificial reproductive tract.
Crucially, the chip-like device not only allows many embryos to be cultured at once, it allows each one to be individually manipulated and tracked in separate channels. That should make it easier to weed out poor-quality embryos before implantation.
Embryologists already inspect embryos under the microscope, and some IVF clinics also measure their consumption of oxygen and glucose and the amount of carbon dioxide they release. All this could be done more routinely on a reproductive chip, says Beebe.
鈥淢ajor questions鈥�
In time, the device could even make it easier to carry out pre-implantation genetic diagnosis, where a few cells are removed to screen embryos for genetic disorders. 鈥淭hat involves more sophisticated manipulation than our current devices can do. But it is something we are working on,鈥� says Beebe.
But quality control raises ethical issues, says Tom Shakespeare of the Policy, Ethics and Life Sciences Research Institute in Newcastle.
鈥淚f we are talking about maximising the chances of becoming pregnant and carrying to term, then there鈥檚 less argument. But if we are talking about either reducing genetic diversity or indeed enhancing selection then there are major questions.鈥�
More at: IEEE Transactions on Biomedical Engineering (vol 48, p 570)
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