Ayoxxa Biosystems

Last updated
Ayoxxa Biosystems
Company type Private
Industry Biotech
FoundedSingapore (2010), Germany (2012)
FounderAndreas Schmidt, Dieter Trau
Headquarters
Cologne
,
Germany
Key people
Albrecht Läufer (CEO),
Markus Zumbansen (CTO)
ProductsDevelopment of a Protein chip platform based on the Bead-based Arrays, named LUNARIS (TM) multiplexing technology
Production output
Biomarker Detection Kits
ServicesMultiplexing and Readout Services, Assay Development Services
OwnerProsnav Capital, and others
Subsidiaries Ayoxxa Inc. (USA), Ayoxxa Living Health Technologies Pte. Ltd (Singapore)
Website www.ayoxxa.com

Ayoxxa Biosystems (stylized in its logo as AYOXXA) is a biotechnology company founded in 2010 in Singapore, and headquartered in Germany. [1] [2]

Contents

The company is known for developing protein chip capable of detecting at once multiple biomarkers, biomarker signatures (including markers for cancer, allergies, age related macular degeneration AMD, or infectious diseases) from a small biological sample. The protein chip yields large amounts of data, being primarily aimed for use in biomedical research in academia, clinic and industry. [1] [3] [4] [5] [6]

History

In 2006 the basic technology of the position-encoded bead-based Arrays multiplex protein chip began to be developed in the research labs of the Department of Bioengineering, at the National University of Singapore (NUS). [1] [3] [7] The project was led by Dieter Trau, Assistant Professor at NUS' Department of Bioengineering and Department of Chemical and Biomolecular Engineering. [1] [3] [8] [9]

As a result, and with the continued support of NUS, the start-up Ayoxxa Living Health Technologies Pte. Ltd was founded in 2010. [1] [5] [7] The rights to the intellectual property developed at NUS were exclusively licensed to Ayoxxa, for the company to further develop. [1]

In 2012 the company expanded operations to Europe, establishing its headquarters in Cologne, Germany, as Ayoxxa Biosystems GmbH. [2] From there the company develops partnerships, services, commercialization and conducts further research. [4] [10] [11]

Between 2010 and 2021 there were multiple rounds of financing, with shareholders including Andreas Schmidt, Dieter Trau, Wellington Partners, NRW.Bank, High-Tech Gründerfonds, Rainer Christine, Gregor Siebenkotten, KfW, b-to-v Partners, Creathor Venture, and HR Ventures. [12] [13] [14] [15]

In 2016 Andreas Schmidt stepped down from the CEO position, later becoming the CEO of Proteona, a single cell analysis and artificial intelligence company. Schmidt remained a board member of Ayoxxa, with Rodney Turner becoming CEO. [16] [17] [18] [19] [20] [21]

In 2022 Ayoxxa closed a new financing round led by Hong Kong-based Prosnav Capital, with the stated goal of bringing funding to support operations and commercialization for 3-5 years. CEO Rodney Turner was succeeded by Albrecht Läufer. [22]

Ayoxxa protein chip I

Ayoxxa's protein chip or microarray technology enables the detection of large number of diseases through the protein analysis of a single droplet of blood or other bodily fluids. [1] [3] [5] [23] This technology contrasts with previously established methods which were restricted to a single point testing, requiring considerable amounts of biological sample, and limiting the amount of analytes tested from each sample. [3] [5] [6] [7] [8]

Microplates.jpg
Example of 96, 384 and 1536 well plates normally used for ELISA
Microarray2.gif
Example of 37,500-probe DNA microarray with enlarged inset to show detail.
Ayoxxa's protein biochip technology is developed to achieve a comparable multiplex protein analysis (simultaneous analysis of multiple components in a single sample)

Instead of yielding one data point at a time (as is the case with classic ELISA), this new technology provides up to 10,000 data points, [24] with efficient labor input, using samples down to 3 microliters (μL) (range of 3 x 10−3 mL). [25] [26] The multiplex technology approaches a level of analytical power (in throughput and accuracy) only previously seen in DNA sequencing arrays. [4] [10]

The protein chip is made of silicon and is used to identify and qualify protein markers for cancer, allergies, cardiovascular or infectious diseases. [5] It simultaneously identifies multiple analytes, and the interactions between them. The technology is developed to run manually as well as fully automated, and giving more results quickly at high-throughput (yielding large amounts of data). The development of this technology is especially directed at the support biomedical research in academic and industry research, [7] [8] with longer-term uses in pharmaceutical screening and preclinical diagnostics. [2] [3] [4] [11] [27]

Protein microarray

Microarrays are built of an 8 cm x 2 cm silicon base plate, or biochip, with dozens of separate 'wells' or containers located on top, each one offering a capacity for up to 20 uL used to incubate with reagents, blocking or washing solutions. Each of these macro-wells, contain thousands of micro-wells at the bottom, each measuring about 1/20th the diameter of a single strand of human hair. [8] [26] [28]

The wells on the chip are filled with antibodies (proteins) linked to microspheres to reside in the cavities. [5] [7] [8] Antibodies by nature are produced by immune cells. They 'bind' specifically to the antigens on the surface of viruses, bacteria, and diseased cells to clear and to prevent health damages to the body. Since antibodies are highly specific proteins, binding to specific antigens, they have been exploited to identify and measure protein biomarkers in immunoassays (e.g. ELISA). [28]

Since different antibodies 'bind' themselves to antigens, this affinity can be exploited for protein analytics by filling the wells with thousands of antibodies, and observing if and how much of a target antigen is present in a sample, or not. Ayoxxa's biochip can be used to identify thousands of different proteins in a single sample, including markers for diseases, where before numerous of the classic ELISA assays would be required to achieve the same results. [3] [7] [10]

Microscopic photograph of microbeads. These are polymer nanoparticles, typically 0.5 to 500 micrometres in diameter. In protein laboratory work, researchers attach different antibodies to different beads, keeping a record of what specific type of antibody each bead contains, and then track those beads in order to observe which ones react when exposed to a sample. Dynabeads are a magnetic type of microbeads.jpg
Microscopic photograph of microbeads. These are polymer nanoparticles, typically 0.5 to 500 micrometres in diameter. In protein laboratory work, researchers attach different antibodies to different beads, keeping a record of what specific type of antibody each bead contains, and then track those beads in order to observe which ones react when exposed to a sample.

To observe the reaction of the different antibodies to the sample, the chip is placed under a standard laboratory fluorescent microscope with a digital camera, which snaps shots of it. It is then possible to electronically analyze and generate data of the different molecules and proteins present in the samples. [1] [23]

In-situ Encoded Bead-based Arrays (IEBA) technology

The technology centers on the patented In-situ Encoded Bead-based Arrays (IEBA), [29] [30] originally developed at the National University of Singapore (NUS), of which Ayoxxa was made the exclusive licensee. [1] [3] [8] Unlike other available bead-based microarrays, IEBA achieves greater multiplexing capability by recording the position of randomly distributed beads without the need for physical labels for bead identification, using instead the assignment of unique coordinates to each bead with an in-house software. [10] [23] [25] [26]

These batches of different beads, each batch being an assay or capture site for a specific biomolecule, are applied sequentially creating a unique pattern for every well. The coordinates of each individual bead in each sequential batch is recorded in a large map/decoding data table that is provided to the user alongside the carrier (like a USB flashdrive). The assay itself follows the sandwich ELISA principle with a read out based on a fluorescent reporter introduced at the final step of the assay. Following imaging using fluorescence microscope technology on the reacted chip, the company's analysis software identifies the individual beads according to their unique signals, later decrypted with the company's software to deliver a customized report to the user. [23] [26] This approach significantly reduces the complexity of downstream analysis while increasing the number of individual protein targets that can be analyzed in very low sample volumes. [10] [23] [25]

Open platform and interoperability

Ayoxxa has stated that its focus is in developing an open and adaptable IEBA platform, that can be easily incorporated into laboratories by being compatible with the existing laboratory technology that researchers are accustomed to using. Furthermore, IEBA is being developed to run with automated liquid handling systems used in high-throughput screening. It has also stated its aim at making the IEBA an open platform, adaptable to the diverse research needs. [25] [26] Ayoxxa's CEO Andreas Schmidt compared the company's open platform philosophy as that of iTunes and iPhone, where many different apps (different biomarkers) run on the iPhone (Ayoxxa's platform). [7]

The IBEAs can be used from low sample numbers up to the standard 384 well plate format, basically being a more advanced ELISA, keeping the current standards and protocols. [23] [25] [26] The arrays are designed to be readily adaptable to standard high throughput screening systems. [10] [25] The IEBA technology can be used with existing bioassays protocols (particularly the bioassays on beads), and readers without the need to invest in a flow cytometer or other capital-intensive devices to read it out. [25] [26]

Recognition

The company has been recognized for its scientific advancements and entrepreneurial drive. [8] Some awards the company received include:

Related Research Articles

<span class="mw-page-title-main">Microarray</span> Small-scale two-dimensional array of samples on a solid support

A microarray is a multiplex lab-on-a-chip. Its purpose is to simultaneously detect the expression of thousands of biological interactions. It is a two-dimensional array on a solid substrate—usually a glass slide or silicon thin-film cell—that assays (tests) large amounts of biological material using high-throughput screening miniaturized, multiplexed and parallel processing and detection methods. The concept and methodology of microarrays was first introduced and illustrated in antibody microarrays by Tse Wen Chang in 1983 in a scientific publication and a series of patents. The "gene chip" industry started to grow significantly after the 1995 Science Magazine article by the Ron Davis and Pat Brown labs at Stanford University. With the establishment of companies, such as Affymetrix, Agilent, Applied Microarrays, Arrayjet, Illumina, and others, the technology of DNA microarrays has become the most sophisticated and the most widely used, while the use of protein, peptide and carbohydrate microarrays is expanding.

<span class="mw-page-title-main">DNA microarray</span> Collection of microscopic DNA spots attached to a solid surface

A DNA microarray is a collection of microscopic DNA spots attached to a solid surface. Scientists use DNA microarrays to measure the expression levels of large numbers of genes simultaneously or to genotype multiple regions of a genome. Each DNA spot contains picomoles of a specific DNA sequence, known as probes. These can be a short section of a gene or other DNA element that are used to hybridize a cDNA or cRNA sample under high-stringency conditions. Probe-target hybridization is usually detected and quantified by detection of fluorophore-, silver-, or chemiluminescence-labeled targets to determine relative abundance of nucleic acid sequences in the target. The original nucleic acid arrays were macro arrays approximately 9 cm × 12 cm and the first computerized image based analysis was published in 1981. It was invented by Patrick O. Brown. An example of its application is in SNPs arrays for polymorphisms in cardiovascular diseases, cancer, pathogens and GWAS analysis. It is also used for the identification of structural variations and the measurement of gene expression.

Affymetrix is now Applied Biosystems, a brand of DNA microarray products sold by Thermo Fisher Scientific that originated with an American biotechnology research and development and manufacturing company of the same name. The Santa Clara, California-based Affymetrix, Inc. now a part of Thermo Fisher Scientific was co-founded by Alex Zaffaroni and Stephen Fodor. Stephen Fodor and his group, based on their earlier development of methods to fabricate DNA microarrays using semiconductor manufacturing techniques.

<span class="mw-page-title-main">Biochip</span> Substrates performing biochemical reactions

In molecular biology, biochips are engineered substrates that can host large numbers of simultaneous biochemical reactions. One of the goals of biochip technology is to efficiently screen large numbers of biological analytes, with potential applications ranging from disease diagnosis to detection of bioterrorism agents. For example, digital microfluidic biochips are under investigation for applications in biomedical fields. In a digital microfluidic biochip, a group of (adjacent) cells in the microfluidic array can be configured to work as storage, functional operations, as well as for transporting fluid droplets dynamically.

A protein microarray is a high-throughput method used to track the interactions and activities of proteins, and to determine their function, and determining function on a large scale. Its main advantage lies in the fact that large numbers of proteins can be tracked in parallel. The chip consists of a support surface such as a glass slide, nitrocellulose membrane, bead, or microtitre plate, to which an array of capture proteins is bound. Probe molecules, typically labeled with a fluorescent dye, are added to the array. Any reaction between the probe and the immobilised protein emits a fluorescent signal that is read by a laser scanner. Protein microarrays are rapid, automated, economical, and highly sensitive, consuming small quantities of samples and reagents. The concept and methodology of protein microarrays was first introduced and illustrated in antibody microarrays in 1983 in a scientific publication and a series of patents. The high-throughput technology behind the protein microarray was relatively easy to develop since it is based on the technology developed for DNA microarrays, which have become the most widely used microarrays.

Invitrogen is one of several brands under the Thermo Fisher Scientific corporation. The product line includes various subbrands of biotechnology products, such as machines and consumables for polymerase chain reaction, reverse transcription, cloning, culturing, stem cell production, cell therapy, regenerative medicine, immunotherapy, transfection, DNA/RNA purification, diagnostic tests, antibodies, and immunoassays.

<span class="mw-page-title-main">Antibody microarray</span> Form of protein microarray

An antibody microarray is a specific form of protein microarray. In this technology, a collection of captured antibodies are spotted and fixed on a solid surface such as glass, plastic, membrane, or silicon chip, and the interaction between the antibody and its target antigen is detected. Antibody microarrays are often used for detecting protein expression from various biofluids including serum, plasma and cell or tissue lysates. Antibody arrays may be used for both basic research and medical and diagnostic applications.

Surface-enhanced laser desorption/ionization (SELDI) is a soft ionization method in mass spectrometry (MS) used for the analysis of protein mixtures. It is a variation of matrix-assisted laser desorption/ionization (MALDI). In MALDI, the sample is mixed with a matrix material and applied to a metal plate before irradiation by a laser, whereas in SELDI, proteins of interest in a sample become bound to a surface before MS analysis. The sample surface is a key component in the purification, desorption, and ionization of the sample. SELDI is typically used with time-of-flight (TOF) mass spectrometers and is used to detect proteins in tissue samples, blood, urine, or other clinical samples, however, SELDI technology can potentially be used in any application by simply modifying the sample surface.

<span class="mw-page-title-main">Autonomous detection system</span> Automated biohazard detection system

Autonomous Detection Systems (ADS), also called biohazard detection systems or autonomous pathogen detection systems, are designed to monitor air or water in an environment and to detect the presence of airborne or waterborne chemicals, toxins, pathogens, or other biological agents capable of causing human illness or death. These systems monitor air or water continuously and send real-time alerts to appropriate authorities in the event of an act of bioterrorism or biological warfare.

Cell-free protein array technology produces protein microarrays by performing in vitro synthesis of the target proteins from their DNA templates. This method of synthesizing protein microarrays overcomes the many obstacles and challenges faced by traditional methods of protein array production that have prevented widespread adoption of protein microarrays in proteomics. Protein arrays made from this technology can be used for testing protein–protein interactions, as well as protein interactions with other cellular molecules such as DNA and lipids. Other applications include enzymatic inhibition assays and screenings of antibody specificity.

<span class="mw-page-title-main">Grace Bio-Labs</span>

Grace Bio-Labs is a global supplier of pharmaceutical, biomedical, and biochemical research products based in Bend, Oregon, United States. They develop the thin-cast nitrocellulose biochip and the modern hybridization and incubation chambers for glass microscope slides.

<span class="mw-page-title-main">Bio-MEMS</span>

Bio-MEMS is an abbreviation for biomedical microelectromechanical systems. Bio-MEMS have considerable overlap, and is sometimes considered synonymous, with lab-on-a-chip (LOC) and micro total analysis systems (μTAS). Bio-MEMS is typically more focused on mechanical parts and microfabrication technologies made suitable for biological applications. On the other hand, lab-on-a-chip is concerned with miniaturization and integration of laboratory processes and experiments into single chips. In this definition, lab-on-a-chip devices do not strictly have biological applications, although most do or are amenable to be adapted for biological purposes. Similarly, micro total analysis systems may not have biological applications in mind, and are usually dedicated to chemical analysis. A broad definition for bio-MEMS can be used to refer to the science and technology of operating at the microscale for biological and biomedical applications, which may or may not include any electronic or mechanical functions. The interdisciplinary nature of bio-MEMS combines material sciences, clinical sciences, medicine, surgery, electrical engineering, mechanical engineering, optical engineering, chemical engineering, and biomedical engineering. Some of its major applications include genomics, proteomics, molecular diagnostics, point-of-care diagnostics, tissue engineering, single cell analysis and implantable microdevices.

<span class="mw-page-title-main">Anti-dsDNA antibodies</span> Group of anti-nuclear antibodies

Anti-double stranded DNA (Anti-dsDNA) antibodies are a group of anti-nuclear antibodies (ANA) the target antigen of which is double stranded DNA. Blood tests such as enzyme-linked immunosorbent assay (ELISA) and immunofluorescence are routinely performed to detect anti-dsDNA antibodies in diagnostic laboratories. They are highly diagnostic of systemic lupus erythematosus (SLE) and are implicated in the pathogenesis of lupus nephritis.

A reverse phase protein lysate microarray (RPMA) is a protein microarray designed as a dot-blot platform that allows measurement of protein expression levels in a large number of biological samples simultaneously in a quantitative manner when high-quality antibodies are available.

<span class="mw-page-title-main">MAGIChip</span>

MAGIChips, also known as "microarrays of gel-immobilized compounds on a chip" or "three-dimensional DNA microarrays", are devices for molecular hybridization produced by immobilizing oligonucleotides, DNA, enzymes, antibodies, and other compounds on a photopolymerized micromatrix of polyacrylamide gel pads of 100x100x20µm or smaller size. This technology is used for analysis of nucleic acid hybridization, specific binding of DNA, and low-molecular weight compounds with proteins, and protein-protein interactions.

<span class="mw-page-title-main">Centrifugal micro-fluidic biochip</span>

The centrifugal micro-fluidic biochip or centrifugal micro-fluidic biodisk is a type of lab-on-a-chip technology, also known as lab-on-a-disc, that can be used to integrate processes such as separating, mixing, reaction and detecting molecules of nano-size in a single piece of platform, including a compact disk or DVD. This type of micro-fluidic biochip is based upon the principle of microfluidics; to take advantage of non-inertial pumping for lab-on-a-chip devices using non-inertial valves and switches under centrifugal force and Coriolis effect to distribute fluids about the disks in a highly parallel order.

Suspension array technology is a high throughput, large-scale, and multiplexed screening platform used in molecular biology. SAT has been widely applied to genomic and proteomic research, such as single nucleotide polymorphism (SNP) genotyping, genetic disease screening, gene expression profiling, screening drug discovery and clinical diagnosis. SAT uses microsphere beads to prepare arrays. SAT allows for the simultaneous testing of multiple gene variants through the use of these microsphere beads as each type of microsphere bead has a unique identification based on variations in optical properties, most common is fluorescent colour. As each colour and intensity of colour has a unique wavelength, beads can easily be differentiated based on their wavelength intensity. Microspheres are readily suspendable in solution and exhibit favorable kinetics during an assay. Similar to flat microarrays, an appropriate receptor molecule, such as DNA oligonucleotide probes, antibodies, or other proteins, attach themselves to the differently labeled microspheres. This produces thousands of microsphere array elements. Probe-target hybridization is usually detected by optically labeled targets, which determines the relative abundance of each target in the sample.

<span class="mw-page-title-main">Peptide microarray</span>

A peptide microarray is a collection of peptides displayed on a solid surface, usually a glass or plastic chip. Peptide chips are used by scientists in biology, medicine and pharmacology to study binding properties and functionality and kinetics of protein-protein interactions in general. In basic research, peptide microarrays are often used to profile an enzyme, to map an antibody epitope or to find key residues for protein binding. Practical applications are seromarker discovery, profiling of changing humoral immune responses of individual patients during disease progression, monitoring of therapeutic interventions, patient stratification and development of diagnostic tools and vaccines.

<span class="mw-page-title-main">CD/DVD based immunoassay</span>

A compact disk/digital versatile disk (CD/DVD) based immunoassay is a method for determining the concentration of a compound in research and diagnostic laboratories by performing the test on an adapted CD/DVD surface using an adapted optical disc drive; these methods have been discussed and prototyped in research labs since 1991.

Signs Of LIfe Detector (SOLID) is an analytical instrument under development to detect extraterrestrial life in the form of organic biosignatures obtained from a core drill during planetary exploration.

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