EQUIPMENT
Microfractor Becomes Useful Research Tool Battelle Memorial Institute refines distillation device, now uses it to separate high molecular weight materials A unique, high-vacuum molecular distillation apparatus has passed through the development stage and is now being put through its first paces as a new analytical research tool at Battelle Memorial Institute. Its job is to resolve mixtures of materials otherwise difficult or impossible to separate, such as steroids and alkaloids. Called a microfractor, the one-of-akind unit is being used initially in a pharmaceutical study sponsored by Abbott Laboratories, explain Battelle scientists Glenn Kinzer and Frederick Benington. It operates with mixtures of materials ranging in molecular weight from about 250 to 1200. And it should be especially useful for separating materials with very close molecular weights.
HOW THE DEVICE WORKS
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The microfractor gets around many of conventional distillation's defects. With traveling steel bands that serve as both evaporators and condensers, the unit gives resolutions equal to that of multiplate distillation. And unlike conventional stills, the unit operates on the principle of least mixing. Each bit of material transferred joins like material, doesn't keep diluting the richer distillate. In conventional distillation of high molecular weight material, condensers and liquid pumps and pipelines must be kept hot so that solid constituents won't block the transfer pipes. The microfractor doesn't present this thermal hazard. It will thus separate many materials that would degrade or decompose during distillation.
Based on its accomplishments to date, the microfractor should do especially well with dyes, alkaloids, and steroids. During try outs it: • Separated a dye mixture of C. I. Solvent Red 1 (m.w. 280), C. I. Disperse Blue No. 3 (m.w. 300), C. I. Solvent Yellow 33 (m.w. 261) into red and blue fractions about 8 5 % pure and a yellow fraction completely resolved. • Separated a synthetic alkaloid mixture of cinchonine (m.w. 294) and papaverine (m.w. 339) into fractions with purities of at least 90%. • Separated a sterol mixture of stigmasterol (m.w. 412) and /^-sitosterol (m.w. 414)—which differ only in that the former has a trans double bond in
Battelle's microfractor consists of a stainless steel U-band with a similar transverse band running between the legs of the U. Heaters and cooling platens cause evaporation and condensation to take place where the bands cross. Material to be separated starts out on the transverse band, where it is laid down the entire length. As the band travels around the rollers, the material passes over a heater. The heater filaments, adjusted to the proper temperatures for a given material, are skewed at an angle. Thus lighter components in the material vaporize first, since they need less heating time than heavier components. Heavier components vaporize toward the end of the pass over the heaters. In this way the heater acts as a plow, continually pushing the heavier molecules to one side. A cooling platen is located on the underside of the U-band directly over the spot where vapor is coming off the transverse band. Vapor thus hits the U-band and condenses. The U-band carries the material, now partially sep-
the hydrocarbon side chain—into fractions with purities of about 80%. Steel Bands. The Battelle unit consists of a stainless steel U-band 6 in. wide with a similar transverse band running between the legs of the U. By means of heaters and cooling platens, evaporation and condensation take place where the bands cross. Distance between bands is about Vs m · Cooling platens are made of brass; copper tubes, soldered to the platens, carry refrigerant. So far Battelle hasn't had any leakage problems with the refrigeration equipment, which operates in the vacuum. Each heater consists of three filaments—preheater, main heater, and afterheater—separately adjusted between 75° and 300° C. to get the proper thermal gradient for the materials being separated. With the heater skewed at the proper angle, then, heavier material vaporizes later than lighter material, which doesn't require as much heating. The heater thus continually pushes the heavier molecules to one side. The transverse band acts as the feed point. In operation, material is laid down the entire length of the band. The equipment is then covered with
a bell jar mounted on rollers, and the chamber evacuated to about 1 to 5 microns Hg pressure. The microfractor is then ready to go. The amount of time to microfract a mixture, Mr. Kinzer points out, depends on the relative volatility of the material involved. Another factor is band speed, which is variable between 3 and 9 in. per minute. Some runs, Mr. Kinser says, have taken as little as 45 minutes to separate 250 to 750 milligrams, depending on the material. The microfractor, however, has a capacity to handle 50 to 1000 milligrams of material for each run, he explains. After separation is complete, an additional heater located on the underside of the bottom of the U-band removes the product. It vaporizes the material onto a condenser, serrated to conform to the fractions. The detachable serrations are then taken apart and the fractions recovered independently by dissolving with solvent. Ratio Limits Resolution. The limiting resolution of the instrument is related to the ratio of the band width to the distance between bands. But in practice, the material's uniformity of composition and thickness of lay-
down play a part to limit resolution. Battelle came on the microfractor in a late stage of development. Invented by Dr. Kenneth Hickman, the microfractor was first sponsored by Arthur D. Little, Inc. Sponsorship ended and development stopped until Battelle stepped in and bought the apparatus and rights to future development. Under Abbott's sponsorship, the institute has been developing the instrument to its present state since early last year. Battelle has just begun to study applications of the microfractor and is continuing to refine the device. But already it is thinking of future developments. One possibility is a continuous device (it's currently a batch operation). Another idea Battelle has in mind is scaling the unit up to one that will handle kilogram quantities. There's no reason, Mr. Benington says, why a device with bands 36 to 40 inches wide couldn't be made. Not only would such a unit process more material, it would also have greater resolving power, since resolution increases with band width. It would probably be used only for expensive materials.
arated, around the upper leg then down to the lower leg. At the point where material on the lower leg of the U-band is crossing under the transverse band, another heater causes it to evaporate. This time the cooling platen is on the underside of the transverse band, and the material condenses back onto the transverse band, reasly to go through the whole operation again. As the bands travel around, then, material evaporates and condenses from band to band. Each time this process occurs, the material separates more and more. Finally each molecular-weight fraction winds up in a separate strip on the bands. When a run, which may take as little as 45 minutes, is complete, the strips of material are printed down onto a serrated condenser by means of a heater (not shown) on the underside of the U-band at the lower leg. The serrations then break apart. In this way, it's possible to recover each fraction separately by dissolving it with solvent. MARCH
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