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RESEARCH PROFILES Modular ___________ biosensor (fill in the blank)
brought into close proximiIt can be altered to detect Displacement + Analyte ty, which establishes fluojust about anything. It is rescence resonance energy fully reversible and reagentProximity-sensitive transfer (FRET). The FRET less, and it easily self-assemsignal transduction Recognition analogue signal serves as a baseline. bles on microwell plates. It When the target analyte is can even be dried and stored added, it competes with the in a refrigerator for several Flexible arm analogue for the recognition weeks and then reconstituted Biorecognition site. As the concentration of and used somewhere else, element the analyte increases, it dissuch as in the field. Specific oriented places the analogue. “Just by The modular biosensor, surface attachment Surface pure kinetics, the analyte will developed by a team of recompete and displace the searchers led by Igor Medanalogue slowly,” says Medintz at the U.S. Naval ReThe modular biosensor shown here can be readily adapted to target just intz. The addition of the ansearch Laboratory, is based about any analyte. alyte changes the FRET sigon a general strategy that nal in a concentration-dependent manner. TNT and its analogues, and the flexible uses multifunctional surface-tethered The sensor can be regenerated several components. The approach was first de- arm contains the TNT analogue 1,3,5times by washing away the analyte. In adtrinitrobenzene. scribed for detecting the sugar maltose dition, the dynamic range can be adjusted In both biosensors, the biorecogni(Anal. Chem. 2004, 76, 5620–5629). by adding complementary DNA, which tion element is tethered to the solid Now, in the January 15 issue of Analytincreases the stiffness of the flexible arm. substrate NeutrAvidin on a microwell ical Chemistry (pp 365–372), Medintz For the next sensor, the researchers and colleagues show that the same sens- plate. A bis-functional chemical called are considering targeting a compound of Bio-X-NTA, which has biotin on one ing strategy can detect a completely unpharmaceutical interest. “The idea there end and nickel-nitrilotriacetic acid related analyte—the explosive 2,4,6would be that you can set this up in a (NTA) on the other, is used to bridge trinitrotoluene (TNT). 96-well plate and screen a variety of difthe biorecognition element to NeutrThe ease with which the sensor can Avidin. The chemical helps keep the pro- ferent compounds for their ability to inbe altered to target new analytes makes teract with a receptor of pharmaceutical it promising for a wide range of applica- tein oriented the right way, which is key interest,” says Medintz. They are also into the sensor’s design. Other surface attions, from homeland security, military, terested in changing what the sensor is tachment methods besides biotin–avidin and healthcare to environmental and attached to, while keeping the principles could be used, such as metal-affinity cofood monitoring. of the sensor the same. “We would like ordination, thiol bonding, hydrophobic The sensor consists of two general to perhaps attach this to something like interactions, and so forth. modules—a biorecognition element and a quantum dot or a fluorescent particle. The challenge is to choose a bioa flexible arm that reacts with the biorecThat might allow it to be introduced recognition element that is going to fit ognition element. To target a different into a cell. That would be very interestand work the way you want it to, says analyte, you just alter those two parts, ing because then you could do some Medintz. “You want to give it oriented says Medintz. microscopy on it,” he says. binding. You want it to be relatively The biorecognition element can be a The possibilities appear to be endless. small. And you want to have the ability protein, aptamer, carbohydrate, DNA or The sensor could be set up for continuto control the sites where you put the RNA molecule, and so forth. It gives ous monitoring of one analyte or even dyes,” he says. Although an anti-TNT the sensor its specificity. It interacts and multiple analytes. It could be used to antibody is commercially available, it is binds with the flexible arm, which condetermine whether a particular analyte is tains a structural analogue of the analyte. much too large to work in the current present or absent. It could be prepared design. Medintz had to make his own In the prototype maltose biosensor, ahead of time and stored indefinitely for site-specifically dye-labeled anti-TNT the biorecognition element was maltose use elsewhere. Perhaps it could even be antibody fragment. After four tries, one binding protein, and the flexible arm shipped ready-to-go, directly from a finally worked, he says. contained a structural analogue of maltBoth the biorecognition element and commercial manufacturer. Just name ose, -cyclodextrin. In the new TNT biosensor, the biorecognition element is the flexible arm are labeled with fluores- your analyte. a —Britt E. Erickson cent dyes. When they bind, they are an antibody fragment that recognizes 50 A
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