Patent Description:
Elasticity is commonly measured by a tensile test: fixing one end of a sample, pulling the other end under a given load, and measuring the sample's deformation. Using similar ideas, the elasticities of tiny fragile fibers, such as DNA/RNA<NUM>-<NUM>, filamentous bacteria<NUM>,<NUM>, actin filaments<NUM>, carbon nanotubes<NUM>-<NUM>, and functional microfibers<NUM>-<NUM> can be measured by advanced equipment such as optical/magnetic tweezers<NUM>,<NUM>, piezo actuators<NUM>,<NUM>,<NUM>, atomic force microscopes<NUM>,<NUM>, transmission electron microscopes<NUM>,<NUM>, and microfluidic devices<NUM>,<NUM>,<NUM>. Recent technological advances have made gains in both sensitivity and accuracy (e.g., measurements on the order of ~pN in force and ~nm in displacement). The throughput, however, remains low and is impeded, for example, by the sample loading and unloading, which is time-consuming and skill-intensive as the fibers of research interest are commonly tiny and fragile.

In<NPL>, there is disclosed a system and an associated method for triggering liquid rope-coiling of viscous micro threads and synthesis of coiled hydrogel microfibers with in-situ gelation. Microfiber based coiled hydrogel structures can be synthesized with flexible shape and dimension control. Complex shaped second-order coiled structures can also be synthesized.

Embodiments of the subject invention can provide a simple microfluidic method and apparatus that measures the elasticity of microfibers (even at high throughput) by rope-coiling, such that sample loading and unloading are not needed between consecutive measurements. Rope-coiling refers to the buckling of a slender elastic fiber caused by axial compression<NUM>. Rope-coiling should not be confused with the coiling of viscous liquid threads<NUM>-<NUM>, nor the subsequent solidification of the already coiled liquid threads<NUM>,<NUM>. Research interest in rope-coiling in liquid has emerged only recently with increasing microfluidic applications.

Without being bound by theory, the inventors expect that the coiling method can be applied to different kinds of samples, including but not limited to DNA, filamentous bacteria, cytoskeleton filaments, and carbon nanotubes, of which the challenges created by various small values of diameter can be overcome by embodiments of the subject invention.

As the inventors have shown, Rcoil ∝ E dfiber, where Rcoil is the coiling radius of fiber, E is the elastic modulus and dfiver is fiber diameter, implies that the coiling radius of a soft but thick fiber can be similar to that of a stiff but thin fiber. In one experiment, the coiling has been demonstrated for very soft microfibers, with elastic moduli ~<NUM> kPa and diameter ~<NUM>. In contrast, for example, DNA can be quite stiff, with elastic modulus ~<NUM> GPa and diameter ~<NUM>, so that the resultant coiling radius can have the same order of magnitude. Furthermore, according to a scaling analysis Rcoil ∝ (E dfiber)/(µ νfiber), where νfiber is injected velocity of fiber and µ is the viscosity of the surrounding liquid, embodiments can also modify the injected velocity, liquid viscosity, fiber diameter and channel size to adapt the setup for different samples. From the technical perspective, despite numerous challenges, there are successful examples in related art of manipulating, uncoiling, and imaging of DNA or actin filaments in micro/nanofluidic chips under an optical microscope. Embodiments of the subject invention advance beyond the related art by providing novel systems and methods for non-destructive measurement of nanofiber and microfiber mechanical properties (e.g., fiber elasticity). Non-destructive measurement means that the measured fiber is not destroyed to obtain the measurement, and includes but is not limited to rapid, non-contact (e.g., image based, light intensity, laser diffraction) measurement of rope-coiling parameters (e.g., coiling radius, the period, the pitch and velocity of coil). Rapid measurement means that the measurement can be obtained while maintaining the throughput of the manufacturing process to within an order of magnitude, and includes but is not limited to measurements wherein sample loading and unloading are not needed between consecutive measurements. Non-contact means that the measurement does not require physical contact with the measured fiber, and includes but is not limited to optical, laser, and light based measurements. Certain embodiments can provide real-time measurement and analysis leading to the identification, classification, sorting, or grouping of fibers during production. Certain embodiments can provide real-time measurement and analysis leading to process control and optimization of one or more fiber properties during production with requiring material reduction in fiber throughput to obtain the measurement.

It is contemplated within the scope of the subject invention that high-throughput measurements of fiber coiling radius according to embodiments of the subject invention can provide new or improved applications such as real-time screening or sorting by provided measurements of mechanical properties and real-time control of process parameters during the production of microfibers.

According to a first aspect of the invention, there is provided a system for high throughput elasticity measurement of a target microfiber, as set forth in the accompanying claim <NUM>.

According to a second aspect of the invention, there is provided a method for high throughput elasticity measurement of a target microfiber, as set forth in the accompanying claim <NUM>.

The subject invention can be better understood by reference to certain non-limiting exemplary embodiments and related definitions, as follows.

In certain embodiments, high throughput elasticity measurement of microfibers can be advantageously applied to continuous or semi-continuous production of a fiber or fibers (e.g., between <NUM> and <NUM> diameter, or larger or smaller, including any fiber that can be rope-coiled) at a measurement rate greater than <NUM> measurement per minute (e.g., greater than <NUM> measurement per second, or faster or slower, including any rate at which the target fiber can be rope-coiled, measured, and optionally uncoiled in a commercially viable production process or measurement process), and at fiber throughput rate greater than <NUM>/sec, alternatively greater than <NUM>/s, alternatively greater than <NUM>/s, or faster or slower, including any rate at which the target fiber can be rope-coiled, measured, and optionally uncoiled in a commercially viable production process or measurement process.

In certain embodiments a coiling device can include two channels (e.g., glass capillaries) selected to form a small channel upstream and a wide channel downstream as shown in <FIG>. In certain embodiments the width of the upstream channel is in the range of hundreds of microns, for example <NUM> has been tested successfully. Alternatively, the width of the upstream channel can be <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, or <NUM> (or higher, depending on the fiber being measured), including increments, combinations, and ranges of any of the foregoing. In certain embodiments the width of the downstream channel is in the range of hundreds of microns, for example <NUM>, <NUM>, or <NUM> have been tested successfully. Alternatively, the width of the downstream channel can be <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, or <NUM> (or higher in certain embodiments, depending on the fiber being measured), including increments, combinations, and ranges of any of the foregoing. In certain embodiments the ratio of the width of the upstream channel to the width of the downstream channel is in the range of about <NUM>:<NUM> to about <NUM>:<NUM>, for example <NUM>/<NUM> (about <NUM>:<NUM>, or about <NUM>), <NUM>/<NUM> (about <NUM>:<NUM>, or about <NUM>), and <NUM>/<NUM> (about <NUM>:<NUM>, or about <NUM>) have been tested successfully. Alternatively, the ratio of the width of the upstream channel to the width of the downstream channel can be <NUM>, <NUM>, <NUM>, <NUM>, or <NUM> (or in certain embodiments either higher or lower, depending on the fiber being measured), including increments, combinations, and ranges of any of the foregoing. Suitable ratios include those low enough to produce the coiling effect in a fiber under measurement conditions while also large enough to remain practical and commercially viable. From a practical perspective, for a given size fiber extruded or passed through a given size upstream channel, one of ordinary skill in the art can, by the teachings of the subject invention, select an appropriate size downstream channel to provide sufficient change in width to produce the coiling effect and allow for the expected coiling and measurement of the fiber.

In certain embodiments a coil measurement device can include optical and/or microfluidic measurement devices, or other devices capable of delivering measurements in the range of seconds, for example <NUM> measurement in less than <NUM> seconds, alternatively less than <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, or <NUM> second per measurement or greater than <NUM>, <NUM>, <NUM>, <NUM>, or <NUM> measurements per second, including increments, combinations, and ranges of any of the foregoing. A coil measurement device cannot include conventional fiber measurement devices (or techniques, methods, or procedures) requiring more than <NUM> minute per measurement.

A coil measurement calibration device can include a physical, digital, or logical lookup table, calibration curve, or equation.

One embodiment is schematically illustrated in <FIG>, which comprises a device for making fibers and a coiling device. The device for making fibers can be a co-flow device, which comprises two coaxially aligned inlets made by a tapered inner capillary contained within an outer capillary, as shown in <FIG>. Microfibers can be produced by polymer crosslinking. For example, using an aqueous two-phase system (ATPS) as a model, the polymer-rich phase, which contains the photoinitiator, can be injected into the inner capillary, while the salt-rich phase can be injected into the outer capillary. A pulsed UV illumination polymerizes the aqueous jet into microfibers as shown in <FIG>, where the microfiber is straight before entering the wide channel in the coiling device. By controlling the reaction conditions precisely, microfibers with different diameters, elasticities, and injection speeds can be produced and evaluated according to the subject invention. Embodiments can measure the elastic moduli of microfibers by calibration to the real-time and non-contact measurement of coil radius. Embodiments have been tested and validated against destructive, expensive, and lower-throughput systems and methods are known in the art (e.g., a conventional tensile tester).

Coiling can occur spontaneously according to an embodiment of the subject invention when microfibers enter a wide channel in a coiling device, as shown in <FIG>. A coiling device according to an embodiment of the subject invention can be made by connecting two glass capillaries (including, for example, microfluidic structures comprising, approximating, or serving as capillaries) to form a small channel upstream and an abruptly enlarged wide channel downstream. The inventors have found that as the elasticity increases (e.g., moving from <FIG>, sequentially through <FIG>, <FIG>, <FIG>, <FIG>, and <FIG>), the coiling radius increases correspondingly. It can be shown that the coiling radius is directly proportional to the elastic modulus of the fiber, and embodiments can advantageously use this relation to measure the elasticity for high-throughput applications. The coiling in the wide channel can be temporary; the collected microfibers are straight without curls at rest, as shown in <FIG> and <FIG>. This observation justifies that the microfibers have been solidified fully before coiling; otherwise, the elastic microfibers would have a curly shape at rest, as demonstrated in related art<NUM>.

Embodiments can analyze the relation between the elasticity and the coiling radius, as shown in <FIG>. These charts show the elastic modulus E and the corresponding coiling radius Rcoil for seven different sets of experimental conditions as shown in the legend of <FIG>: either the fiber velocity νfiber, the fiber diameter dfiber, or the half-width of the wide channel R<NUM> can be varied. Linear relations are observed in all seven data groups, as shown in <FIG>, where the solid lines are the best fits. The inventors have also determined that the slope E/Rcoil decreases as dfiber increases, as shown in <FIG>. The exponent of the best fit (solid line) is -<NUM> ± <NUM>, which shows Rcoil ∝ E dfiber. Therefore, with a proper calibration on the slope E/Rcoil, embodiments can use the linear relation to measure the elasticity from the coiling radius in a continuous flow, high-throughput setting.

Coiling methods according to embodiments of the subject invention can have several advantages over conventional pulling methods for analyzing elastic properties of fibers. For example, the throughput of certain embodiments can be up to or more than tens, hundreds, or thousands of times higher than the comparable throughput of a tensile tester. This is at least in part because in the microfluidic device it takes only one second or less than one second to measure a single microfiber. To do the same measurement on a tensile tester, using related art methods, it takes <NUM> minutes to complete each measurement, in part due to the skill-intensive process of loading/unloading fragile samples. One important bottleneck of the pulling method can be (e.g., for tiny and/or fragile samples) the time-consuming and skill-intensive process of sample loading and unloading. Due to the high time and labor cost, the quality of the fibers can only be assessed statistically with sampling. In contrast, for the continuous flow coiling methods provided by embodiments of the subject invention, sample loading and unloading are not needed between consecutive measurements, so certain embodiments can measure the elasticity of every microfiber in real time (e.g., taking one measurement per second, or one measurement per minute, or faster or slower, as determined according to the stability of the fiber manufacturing process) by automatic video, image, or other sensor data analysis (e.g., by optical, microscopic, or microfluidic techniques). Alternative embodiments can measure select microfibers, can measure asynchronously or in parallel, and can measure by alternate sensors utilizing methods known in the art, herein disclosed, or later developed.

Additionally, the coiling method enables embodiments to achieve an in situ on-line measurement in a microfluidic production line, as demonstrated in <FIG>, which can couple the "making of microfibers" and the "measurement of elasticity" on the same process line. During or immediately after production, the elasticity of select fibers, or in certain embodiments the elasticity of every fiber, can be measured. Embodiments can screen defective fibers and use a feedback mechanism to correct a production fault or to tune a production process to avoid faults, improve throughput, increase quality, or optimize the process. For example, to maintain a constant elasticity, a decrease in coiling radius downstream could trigger an increase in UV intensity upstream.

Further, embodiments can measure the local elasticity of a segment with a spatial resolution on the order of the coiling radius rather than that of the whole fiber. This heterogeneity is demonstrated in <FIG>, which shows the coiling of a fiber with graduated elasticity by changing the UV intensity over time. The inventors have demonstrated that the coiling radius can be small at the soft end, but large at the stiff end of a variable elasticity fiber. To achieve a comparable measurement of the variation of the elasticity by the conventional pulling method, it is necessary to cut a fiber into many pieces and measure each separately, which is an intrusive measurement and substantially increases the time and labor costs.

Following are examples that illustrate procedures for practicing the invention. These examples should not be construed as limiting. All percentages are by weight and all solvent mixture proportions are by volume unless otherwise noted.

The device for making fibers is a microfluidic co-flow device with pulsed UV illumination. The co-flow device consists of two coaxially aligned inlets made by a tapered inner circular capillary in an outer square capillary, as shown in <FIG>. The tapered capillary in <FIG> has an inner diameter of approximately <NUM>.

Microfibers are made of polyethylene glycol diacrylate (PEGDA) and can be cured by UV illumination. <FIG> shows a produced microfiber with a diameter of <NUM>. By adjusting the intensities of UV light (maximum intensity is <NUM> mW/cm<NUM>), microfibers with different elasticities (<NUM>-<NUM> kPa) are fabricated, as shown in <FIG>.

The coiling device is made by connecting two glass capillaries to form a small channel upstream and a wide channel downstream as shown in <FIG>. The width of the upstream channel is <NUM>. The width of the downstream channel is either <NUM>, <NUM> and <NUM> in three different experiments respectively.

Coiling occurs when the microfibers enter the wide channel downstream, as shown in <FIG>. In an example shown in <FIG>, the diameter of the microfiber is <NUM>, the elasticity of the microfiber is <NUM> kPa, the injected velocity of microfiber is <NUM>/s, the width of the downstream channel is <NUM>, and the resulting coiling radius Rcoil is <NUM>.

We also carry out experiments for different experimental conditions (fiber elasticities, fiber velocity, fiber diameter, and channel size) and measure the resulting coiling radius, as shown in <FIG>. The experimental results show that the coiling radius is linearly proportional to the elastic modulus of the fiber. The experimental results demonstrate that we can measure the elasticity of fibers by the coiling method.

Claim 1:
A system for high throughput elasticity measurement of a target microfiber, the system comprising:
a rope-coiling device configured and adapted to induce rope-coiling in the target microfiber, thereby creating a coiled microfiber;
a measurement device configured and adapted to measure one or more physical properties of the coiled microfiber within the rope-coiling device, thereby creating a coiled microfiber measurement; and
a calibration device configured and adapted to convert the coiled microfiber measurement to a microfiber elasticity measurement.