Available Technology
Simple, cost-effective, and tunable density-based separation, purification, and analysis of biological samples
Technology:
Biological analytes are separated based on their density via the use of a multi-phase system. Magnetic levitation is used to create tunable density systems for broader measurement capabilities.
Markets Addressed
Multi-phase systems typically consist of immiscible, aqueous solutions of polymers or surfactants. When such immiscible liquids are mixed, they spontaneously phase-separate into discrete phases/layers, ordered according to density. Complex samples introduced into this multi-phase system separate into distinct components and these components migrate to different layers characteristic of their densities. This density-based separation allows for visual analysis of individual component properties. The samples migrate through the multi-phase system based on gravity or centrifugation.
This method can be used to purify (and extract) or visually check (with the naked eye) for the presence of impurities (pathogens, pests, heavy metals, pesticides) in various samples, such as food, drugs, or plants. This technique can also be used to analyze biological samples, such as cells, for diseases or infections.
Innovations and Advantages
Due to the large variety of polymers, surfactants, and additives than can be mixed to create multi-phase systems, there is a vast number of possible applications for this technique. The phase components can be selected to be biologically compatible to allow for the separation and analysis (or study) of living organisms or cells without affecting viability. Biological samples (saliva, blood) can be separated from non-biological samples (rock, debris) in a forensic science context.
This technique is sensitive enough to detect differences in densities as low as 0.001 g/cm3. Because this multi-phase separation is spontaneous and stable, this technique does not require any calibration, and it is possible to use these systems without centrifugation for certain applications. Even when centrifugation is required, a simple egg-beater centrifuge (i.e. portable, hand-operated) can be used.
The use of aqueous polymers that exhibit limited interaction to create multi-phase systems provides additional advantages: they are easy to prepare, they are stable and amenable to long term storage, and they are versatile (with easily altered composition and density). The multi-phase system can also be enclosed in many different containers (vials, tubes, plates) and can even be deposited on paper, cloth, or string.
As an example, it was demonstrated that an egg-beater centrifuge can be combined with an aqueous polymer multi-phase system to create a low-cost, point-of-care test for diagnosing malaria in the field with only 10 µL of blood, and without any sample preparation or microscopy.
Even when the analytes of interest do not differ in density from other objects or impurities in the sample, these analytes can be tagged (vie binding or other interactions) to a molecule or object that changes its density, allowing for its separation. This technique can be used to identify infections and diseases. For example, cancer cells or cells infected with certain viruses can be selectively tagged (due to the cell’s expression of specific proteins) and subsequently separated.
By combining multi-phase systems with magnetic levitation, a tunable approach to the separation and analysis of materials emerges. By adding paramagnetic solutes and applying a magnetic field to the multi-phase system, one can create tunable density gradients in the density steps/layers of the phase-separated system without the need for centrifugation. Thus, this system allows for the analysis of a wider density range than is possible with the multi-phase system or with magnetic levitation alone, further expanding the field of possible applications of this density-based separation technique.
The use of multi-phase polymer systems with magnetic levitation provides a tunable, cost-effective, portable, and easy-to-use density-based analysis and purification technique for biological samples.
Additional Information
Intellectual Property Status: Patent(s) pending
Related to case HU4195
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Inventor(s):
Kumar, Ashok A.
Mace, Charles R.
Whitesides, George M.
Wirth, Dyann F.
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For further information, please contact:
Mick Sawka, Director of Business Development
(617) 496-3830
Reference Harvard Case #4261