Bioprocess engineering deals with the design and development of equipment and processes for the manufacturing of products such as agriculture, food, feed, pharmaceuticals, nutraceuticals, chemicals, and polymers and paper from biological materials. The basic techniques of bioprocessing date back thousands of years with manufacture of beer, yogurt and bread. Niazi inventions reinvent the entire field of bioprocessing providing inventions into design of bioreactors, mixing systems, monitoring systems, contamination control, capture systems and finally purification of highly sensitive human use products.
- Upstream steps involve growth of genetically modified or unmodified living entities to express a desired product. Current bioreactors date back to thousands of years and even in their modern layout to over 180 years; a ground-up reinvention of upstream technology is developed by Niazi emphasizing use of single-use bioreactor, with minimal energy input, high reproducibility of complex products, operation uncontrolled environment and maximal protection during processing to address the futuristic needs of bioreactors to produce monoclonal antibodies and organs, on demand. These bioreactors open new research and development, fast to market, opportunities, all of which make high-end present and future therapies more affordable. The diversity of inventions provided here range from single-use systems, bioreactor exhaust controls, bioreactor monitoring and capture and purification in the bioreactor.
- Downstream: Harvesting and purification steps are the most expensive steps with greater risk to quality of products. Novel methods of combining capture steps with upstream reduce the cost significantly and improve the quality of products. Methods of capturing and purification of chemicals and drugs are refined to allow low cost manufacturing of biological products. Bioreactors are used for expressing a variety of chemicals and drugs; the next phase after upstream operation is capture and purification, the two steps that have historically required centrifugation and filtration, both of which cause significant loss of product and deterioration of product quality. The inventions described below use a method of first capturing the expressed product and then discarding the contents of bioreactor, eliminating two major costly steps. It is now possible to use a bioreactor to express and purify a product within the same container.
Multiple bioreactor containers vertically disposed allowing gravitational flow through for continuous processing, recycling and protecting environment from exhaust allows processing of every category of product made in a bioreactor at a lower cost. PDF.
A septum is positioned within a disposable vessel and defines a lower chamber and an upper chamber. The septum includes a plurality of apertures that provide fluid communication between the upper chamber and lower chamber. Compressed gas is introduced in the lower chamber to produce fine bubbles rising throughout the vessel to produce a mixing and gasification needed for the growth of a biological culture and manufacture of a biological product in a nutrient medium. Adding a binding resin to the upper chamber allows harvesting, separation and purification of biological products in the reactor as a single unit operation. PDF
Reactors that allow mixing and gasification by converting the entire floor of the reactor vessel to a sparge filter is described. A flexible horizontally disposed disposable bioreactor bag or a stainless steel structure disposed vertically are described, wherein gas is introduced through a perforated septum to aerate the nutrient medium. PDF
Bioreactors operating in uncontrolled environment such as required in situations like on-site production, handling extremely hazardous materials, etc., require a bioreactor that is completely closed. The exhaust is scrubbed of any components of exhaust such as carbon dioxide and entire exhaust gas returned to bioreactor with added nutrient gases, in a one-way operation. Many applications in related industries. Reduces cost of operations by not requiring clean rooms. PDF
Stationary bioreactors and mixing vessels fitted with single-use flexible bags utilizing wave hydrodynamic principle are described for use in every type of biological process and products. Flaps are synced to create a harmonic motion or operated independently to any desired motion. Used for mixing, bioprocessing, chemical reaction with no limitation on size since the container remains stationary. PDF
A single-use round flexible mixing bag where in culture media is agitated using an internal fluid-agitating element comprising a radial flow impeller driven by an internal pneumatic vane motor. The single-use container remains stationary, allowing large volumes for mixing and bioprocessing at a very low cost. PDF
Pressurized hermetically sealed bags disposed inside a cylindrical support and containing a septum with variable density of porosity and dividing the bag into two chambers are used to provide optimal mixing and gasification of nutrient media to grow a variety of biological cultures, particularly the cell cultures to produce a multitude of pharmaceutical and biotechnology products in a disposable system. PDF.
Another patent application for device claim is pending under: US 15/053,804 | Pivoting Pressure Single Use Bioreactor.
A flexible disposable bioreactor having three, stagger-baffled compartments wherein the middle compartment houses a sparging rod is described to provide the highest degree of sparging and mixing to produce biological products. PDF
A method of homogeneously mixing the contents of a plurality of bioreactors by providing a receiving container to receive a fixed fraction of each bioreactor content repeatedly raising and lowering the receiving container to a position above or below the position of the bioreactors resulting in mixing the contents of the bioreactors. PDF
A bioreactor that combines the steps of recombinant expression and separation of a biological product by binding the secreted biological product with a resin, discarding the nutrient medium and eluting the biological product as a concentrated solution, eliminating the steps of sterile filtration and volume reduction. The method also allows loading of resin for column-purification, eliminating all steps of perfusion process and maintaining a sink condition of a toxic product in nutrient medium to optimize productivity of host cells. The instant invention also allows harvesting of solubilized inclusion bodies after the cells have been lysed and refolding of proteins inside the bioreactor. PDF.
A vertical sparging element with pores smaller than about 50 mu and oriented vertically allows uniform distribution of gases and uniform mixing; the size of pores is adjusted to allow for pressure drop from the source of gas connection. PDF
A multi use bioreactor that is a single-use bioreactor, a development bioreactor, a commercial manufacturing bioreactor, a batch, a fed-batch, a perfusion and continuous bioreactor, a convective heat bioreactor, a product capture bioreactor, an ISO 9 bioreactor, a eukaryotic bioreactor, a prokaryotic bioreactor, a technology transfer-free bioreactor, and an inexpensive bioreactor is disclosed. PDF
An aeration and mixing device for disposable flexible bioreactors comprising a mesh of interconnected perforated disposable tubes to form a structure to cover essentially the entire bottom surface of a disposable flexible bioreactor and wherein a continuous flow of gases through the perforations in the tubes provides an aeration and a mixing function. ALLOWED
Cooling or freezing bioreactor exhaust to remove droplets, returning liquid back to the bioreactor and exhausting clean gas. A one-way exhaust to prevent contamination to flexible bioreactors. Low cost, prevents batch losses due to filter blockage, a major risk in upstream processing. PDF
A recirculating bioreactor exhaust apparatus to remove a gaseous element from the bioreactor exhaust, such as carbon dioxide, by freezing the gaseous element and then returning the remaining exhaust gas to the bioreactor and a method of use. PDF
A pair of receptacles capable of housing an emitter probe and a detector probe installed inside a bioreactor to monitor the properties of the nutrient media without contacting the nutrient media. PDF
A pair or receptacles capable of housing an emitter probe and a detector probe are installed inside a bioreactor to monitor the properties of the nutrient media without contacting the nutrient media. method for monitoring a nutrient media in a bioreactor comprising: a. Disposing in a bioreactor at least one pair of receptacles suitable for housing an emitter probe or a detector probe wherein each receptacle comprises one open end in fluid communication with the outside of the bioreactor and one sealed end; b. Disposing an emitter probe in a one receptacle of the pair of receptacles; c. Disposing a detector probe in the other receptacle of the pair of receptacles; d. Adjusting the direction of the emitter and the detector probes to face each other to read transmitted radiation or to an angle to read diffraction of radiation; e. Activating the emitter and detector probes to record transmission or diffraction of the radiation applied to the nutrient media of the bioreactor. PDF
Large-scale downstream processing method of secreted recombinant proteins is provided in a single device, wherein the contents of a plurality of bioreactors are combined simultaneous to their harvesting and purification resulting in significant savings of time and the cost of manufacturing. PDF
A buoyant device containing chromatography media performs the function of protein harvesting replacing the steps of cell separation and volume reduction; the device can be loaded into columns for further purification. The device rotates automatically under Brownian motion caused by strategically placed holes in the buoyant collar. PDF
A device claim based on continuation of US 8,932,843. PDF
A methods claim patent based on continuation of US 8,932,843 for harvesting refolded proteins. PDF
A chromatography column that captures components in a process liquid in a free flow state and allows elution in steps is described. A disposable preparative chromatography column for effecting separation of components of a process liquid. Provisions are made for separating bound protein with resin and elution with purification steps. PDF
A methods claim patent based on continuation of US 9,284,346. PDF
A device claim for continuation of US 9,284,346. PDF
A purification and separation treatment assembly (PASTA) for biological products expressed in a bioreactor comprising a flexible porous tube filled with a binding resin and having a plurality of pores smaller in size than the size of the binding resin and sealed at both ends and at regular distances along the length of the mesh tube. A method for harvesting and purifying a target biological product at the end of a production cycle or during a production cycle. PDF
A method claim application continuation of US 8,852,435. PDF
A method of manufacturing biological products in a single container from the growth of cells to purification of the product is performed in a flexible disposable bioreactor that uses only a compressed gas for mixing and gasification. A porous septum is used to create the gasification and mixing as well as to separate a chromatography media used to harvest and purify a biological product in the same container. The closed container can be used in any environment without the risk of contamination to the product or the risk of contamination of environment with the product. This allows large manufacturing of hazardous substances, drugs and vaccines anywhere at the lowest cost possible. Numerous applications can be found in counter-terrorism and biodefense operations as well in managing epidemic illnesses. PDF
A modular device comprising one or more porous substrate subunits comprising a binding substrate that can interact with a target biological product, either during, or at the end of a manufacturing cycle; and methods of using the device to harvest or purify a biological product. ALLOWED. PDF
Methods of harvesting proteins directly from bioreactors to avoid at several steps in the purification of recombinant drugs are disclosed. A method of harvesting a target protein from a liquid in a first container comprising: A means of contacting said target protein with a resin capable of binding substantially all of said target protein to form a protein-resin conjugate; A means of separating said protein-resin conjugate from said liquid; A means of recovering said target protein from said protein-resin conjugate. PDF