IBM tips microfluidic device for immunodiagnostics

November 18, 2009 – Scientists from IBM Research in Zurich, Switzerland, have created a diagnostic test using a silicon chip to more quickly diagnose diseases.

Their collaborative work with the U. Hospital of Base, published in the December issue of Lab on a Chip, uses capillary forces — the process whereby liquid rises in narrow tubes, or drawn into tiny openings — to analyze tiny samples of serum or blood to find disease markers, typically proteins detectable in human blood.

How it works: 1μl sample is pipetted onto a silicon-compound chip (1cm×5cm), and pushed by a 180μm capillary pump through a set of "micrometer-wide channels" onto a series of mesh structures, which prevent clogging and formation of air bubbles. It then passes through a region containing tiny amounts of a detection antibody (70 picoliters) with fluorescent tags, which recognize and attach to disease markers in the sample. Then, in a 30μm x 20μm "reaction chamber," the tagged disease markers are captured, and upon them shone a focused beam of red light so they can be viewed using a portable sensor device; the amount of light detected indicates the strength of the disease marker in the sample, which helps doctors determine the next course of action.

The flow takes about 15secs, "several times faster than traditional tests," IBM notes, and can be adjusted up to several minutes for reading more complex disease markers. The test could, for instance, be applied immediately after a myocardial infarction (heart attack) to help doctors more quickly take a course of action, and help predict patient survival rate.

Click to Enlarge
Layout of the 1cm×5cm microfluidic chip. The sample is pipetted onto the chip area and pushed through the mesh structure at a regular flow rate (a) by capillary forces created by a pump (d); then through serpentine tunnels (b) to prevent clogging and air bubble formation, and where antibodies have been deposited to recognize and attach to the sample; and then led into a "reaction chamber" (c) to be examined.

From the paper abstract:

The microfluidic elements comprise a sample collector, delay valves, flow resistors, a deposition zone for dAbs, a reaction chamber sealed with a polydimethylsiloxane (PDMS) substrate, and a capillary pump and vents. Parameters for depositing 3.6nL of a solution of dAb on the chip using an inkjet are optimized and the PDMS substrate is patterned with analytes, which provide a positive control, and cAbs. Various storage conditions of the patterned PDMS are investigated for up to 6 months revealing that storage with a desiccant preserved at least 51% of the activity of the cAbs. C-reactive protein (CRP), a general inflammation and cardiac marker, is detected using this one-step chip using only 5μL of human serum by measuring fluorescent signals from 30 × 100μm2 areas of the PDMS substrate in the wet reaction chamber. The one-step chip can detect CRP at a concentration of 10ng mL-1 in less than 3min and below 1ng mL-1 within 14min.

(Lab on a Chip also has posted
a movie describing the process.)

The test "is portable, fast, and requires a very small volume of sample," according to Emmanuel Delamarche, scientist at IBM Research-Zurich. Its small size lends to various formfactors such as credit cards, pens, or "something similar to a pregnancy test," and with its speed "doctors […] can make informed and accurate decisions right at the time they need them most to save lives." Aside from disease diagnosis, potential applications include testing for chemical and bio hazards.

"This microfluidic chip is the next step in the evolution of point of care devices," stated Thierry Leclipteux, CEO/chief science officer of Coris BioConcept, a biotech company developing rapid tests for diagnosing enteric and respiratory pathogens.


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