AMMP Technology – Acoustic Membrane Microparticle Technology

BioScale’s Acoustic Membrane and Microparticle (AMMP™) technology platform is a quantitative, ultra-sensitive system for life sciences and diagnostics applications. AMMP technology integrates the well-developed elements of MEMS sensors, biological capture strategies, and microparticles into a deployable system that outperforms the existing gold standard for quantitative picogram-level detection.

Our AMMP-based systems use either a fully automated 96-well plate assay stations for higher throughput, or a manual system that processes eight samples in parallel for research.

The performance of AMMP technology has been demonstrated across a wide variety of analytes — antibodies, bacteria, viruses, proteins, hormones, DNA and small molecules. , and The platform can accommodate samples from a variety of matrices — cell culture sups, whole blood, serum, plasma, urine, food, and stool. AMMP technology enables scientists and clinicians to evaluate fundamental questions at biologically relevant levels in a simple, flexible, and user-friendly format.

Components

Figure 1: Cartridge Components. A. Eight-sensor MEMS chip B. Chip mounted on disposable cartridge with separate fluidic paths C. Magnetic microparticles

Basic Elements of AMMP Technology

BioScale’s AMMP technology platform integrates three elements for ultra-sensitive quantitative detection:

1. Disposable chip cartridge
2. Biological capture agents
3. Magnetic microparticles

As shown in Figure 2A, Piezoelectric materials can be used to transform electrical and mechanical energy.  The piezoelectric materials are used to both shake and sense a membrane on the order of 20 million times/sec. According to basic physics, the high-order resonance frequency of membrane oscillations change when mass is added or subtracted from the membrane (Figure 2B). Mass, such as an analyte complex, is attached to the membrane using a biological capture agent – often an antibody (Figure 2C).  Magnetic microparticles (Figure 2D) help to enhance the speed and efficiency of analyte capture . The microparticles capture the analyte, minimize sample matrix interference, provide rapid transport of captured analytes to the sensor surface, and provide the bulk of the sensor loading, thus resulting in a measurable signal that is tracked by observing the sensor response.

The exquisite sensitivity of the resonating membrane, the functionalization of the surface of the membrane with a capture agent that specifically binds the analyte of interest, and the signal enhancement through the use of magnetic microparticles combine to make the sensor highly specific, sensitive and robust in a complex matrix.

Figure 2: A. Piezoelectric materials convert motion into electrical signal—or vice-versa B. Change in loading affects frequency C. Biological capture agents D. magnetic microparticles coated with capture agents

Basic Assay Format

Generally speaking, assays are performed as shown in Figure 3, using a modified immunoassay sandwich format in which analytes are captured between the functionalized sensor surface and a functionalized magnetic bead. Samples are first incubated with the specific capture agent (e.g., an antibody) that has been affixed to magnetic beads (Figure 3A).

The mixture of sample plus magnetic microparticles is then delivered to the functionalized membrane sensor for measurement by a series of automated steps under continuous flow (Figure 3B). As the mixture is presented to the sensor, a magnetic field behind the sensor pulls down the magnetic microparticles.  Some of these microparticles have the target analyte attached to them and others do not.  This loading of magnetic microparticles onto the sensor creates a change in frequency of the sensor. 

Next, the magnet is released (Figure 3C) and only the biologically bound beads remain attached to the sensor. The beads without the analyte of interest are washed away, causing another mass change on the membrane that results in another change in frequency.

The system detects this frequency change in a highly precise and quantitative way, yielding a dose-response curve (Figure 3D). Sensor surfaces are regenerated for subsequent use. The overall process takes 10-15 minutes.

AMMP Technology is flexible enough to configure other formats, such as competition assays.

Figure 3: A: Magnetic microparticles are mixed with the sample and bind to the desired analyte. B: The sample is introduced to the sensor surface with the magnet engaged. C: Biologically bound beads remain attached to the sensor when the magnet is removed. D: Change in natural frequency vs. analyte concentration yields a dose-response curve