The Enigma ML has a modular, easily scalable architecture providing flexibility and choice in different healthcare settings. At entry level with a single processing module it is a compact, portable, inexpensive instrument ideally suited to settings where usage is lower and space is a premium e.g. in the doctor's office, pharmacy or intensive care unit. At the other end of the scale, multiple processing modules can be controlled by a single master unit allowing random-access, parallel running of different samples and tests.

It incorporates a clever, disposable cartridge which can accommodate either liquid or swab samples without any requirements for manual processing. All reagents and sample preparation tools are held on the self-contained cartridge and all steps are automated, minimising the risk of human error. The instrument also has a simple to use touch-screen for data entry and result reporting, plus an integrated label printer.

The system can perform multiplex, real-time PCR assays for both DNA and RNA targets.

Key features:

Fully automated real-time PCR system

rapid test (30 ~ 45 minutes to result)

multi-sample and scalable

accepts swabs and liquids (e.g. urine, blood plasma)

integrated sample preparation and analysis

low system price

small footprint (no specialist skills or cold storage requirements)

Press release: ENIGMA DIAGNOSTICS SHOWCASES ITS UNIQUE FULLY AUTOMATED rtPCR BASED ML (MINI-LABORATORY) INSTRUMENT FOR POINT-OFCARE TESTING AT MEDICA 2009... (.pdf)

Product page: Enigma ML ...

Here are the five functional stages of the device:

Stage 1: A one microliter sample, 50 times smaller than a tear drop, is pipetted onto the chip, where the capillary forces begin to take effect.

Stage 2: These forces push the sample through an intricate series of mesh structures, which prevent clogging and air bubbles from forming.

Stage 3: The sample then passes into a region where microscopically small amounts of the detection antibody have been deposited. These antibodies have a fluorescent tag and similar to the antibodies within our body, they recognize the disease marker and attach to it within the sample. Only seventy picoliters (a volume one million times smaller than a tear) of these antibodies are used, making their dissolution in the passing sample extremely fast and efficient.

Stage 4: The most critical stage is called the "reaction chamber" and it measures 30 micrometers in width and 20 micrometers in depth, roughly the diameter of a strand of human hair. Similar to a common pregnancy test, in this stage the disease marker that was previously tagged is captured on the surface of the chamber. By shining a focused beam of red light, the tagged disease markers can be viewed using a portable sensor device that contains a chip similar to those used by digital cameras, albeit this one being much more sensitive. Based on the amount of light detected, medical professionals can visually confirm the strength of the disease marker in the sample to determine the next course of treatment.

Stage 5: Less a stage and more a part of the entire process is the capillary pump. The capillary pump, which has a depth of 180 micrometers, contains an intricate set of microstructures, the job of which is to pump the sample through the device for as long as needed and at a regular flow rate, just like the human heart. This pump makes the test accurate, portable and simple to use. IBM scientists have developed a library of capillary pumps so that tests needing a variety of sample

More from IBM Research: IBM Scientists Reinvent Medical Diagnostic Testing ...

Abstract in Lab on a Chip: Toward one-step point-of-care immunodiagnostics using capillary-driven microfluidics and PDMS substrates

Features from the product page:

Monitoring of device and alarm states by colored icons

Read and optional write access to process values and set- points

Online charts

Monitoring of all available reactors from multiple parallel systems

Supports network encryption and authentification

Supports DASGIP Control user levels and passwords.

Uses Microsoft Silverlight or Apple Software technology

DASGIP Remote Control meets IT security standards and can be configured according to various IT requirements. Depending on additional services provided at site, extended access may be possible:

Mobile access using iPhone and UMTS

Home access from Windows PC or Mac using a VPN connection

Product page: Remote Access from iPod and Webbrowser to DASGIP Control...

Press release: DASGIP Bioreactor System on the iPhone...

IBM Research is working to optimize a process for controlling the rate at which a DNA strand moves through a nano-scale aperture on a thin membrane during analysis for DNA sequencing. While scientists around the world have been working on using nanopore technology to read DNA, nobody has been able to figure out how to have complete control of a DNA strand as it travels through the nanopore. Slowing the speed is critical to being able to read the DNA strand. IBM scientists believe they have a unique approach that could tackle this challenge.

To control the speed at which the DNA flows through the microprocessor nanopore, IBM researchers have developed a device consisting of a multilayer metal/dielectric nano-structure that contains the nanopore. Voltage biases between the electrically addressable metal layers will modulate the electric field inside the nanopore. This device utilizes the interaction of discrete charges along the backbone of a DNA molecule with the modulated electric field to trap DNA in the nanopore. By cyclically turning on and off these gate voltages, scientists showed theoretically and computationally, and expect to be able prove experimentally, the plausibility of moving DNA through the nanopore at a rate of one nucleotide per cycle - a rate that IBM scientists believe would make DNA readable.

Image: A membrane containing the nanopore, funtionalized with metal contacts (orange) separated by dielectric materials (lime), devides a reservoir into a top part containing an ionic solution with a high concentration of single stranded DNA, and a bottom part, where the DNA will be translocated to. The DNA on the top reservoir is induced to go to the bottom reservoir by the action of a biasing voltage. In the absence of anything else, the DNA would translocate through the pore at a speed of several million bases per second. To control the passage of DNA trhough the nano-hole, voltages of appropriate polarity (not shown) are applied to the metal contacts inside the pore, which create an internal electric field that trap the DNA. By alternating the trapping voltages applied to the metal contacts, the DNA can be made ratchet from the top to the bottom reservoirs in a controlled way.

(hat tip: Engadget)

By integrating low-power CMOS electronics into the silicon photomultiplier chip, the team at Philips has developed a digital silicon photomultiplier in which each photon detection is converted directly into an ultra high speed digital pulse that can be directly counted by on-chip counter circuitry. In contrast to conventional silicon photomultipliers, the Philips digital silicon photomultiplier is therefore an all-digital (digital-in/digital-out) device. As a result, it produces faster and more accurate photon counts with extremely well defined timing of the first photon detection, both of which are important factors in applications such as medical imaging scanners and high-energy nuclear particle detectors.

The PET system detects pairs of gamma rays (high energy electromagnetic radiation) originating from a radioactive tracer, a small amount of which is injected into the patient prior to the scan. To image metabolic activity, PET typically uses a radioactive derivative of glucose called fluorodeoxyglucose (FDG). This compound mimics the behavior of glucose in the body and can be detected by the PET system.

For so-called ‘time-of-flight’ PET scanners, accurately determining the time at which the first photon arrives at the detector is extremely important. Philips’ digital silicon photomultiplier prototypes achieve a timing accuracy for the detection of the first photon of around 190 ps (full-width, half-maximum using a standard scintillator crystal (LYSO) at 511 keV for two detectors in coincidence).

Conventional silicon photomultipliers (SiPMs) consist of a two-dimensional array of avalanche photodiodes (APDs) each of which is connected in series with its own polysilicon ‘quenching’ resistor. All of these diode/resistor ‘microcells’ are then connected in parallel and the entire microcell array is reverse-biased to a voltage above the diodes’ normal breakdown voltage – typically in the range 30V to 70V. Operating in this so-called ‘Geiger mode’, the diodes are ultra-sensitive to single electron-hole pairs that result in individual diodes experiencing avalanche breakdown. These electron-hole pairs can be generated either by the absorption of a photon (the desired signal), or by thermal energy or electron tunneling (unwanted background noise). The unwanted background noise produced by thermally generated electron-hole pairs and/or electron tunneling, together with false counts due to defective microcells, are collectively referred to as the SiPM’s ‘dark count’.

To eliminate a conventional SiPM’s need for an external digitizing ASIC, the digital silicon photomultiplier developed by Philips equips each individual avalanche photodiode with its own 1-bit on-chip ADC (Analog to Digital Converter) in the form of a CMOS inverter. Each microcell that experiences avalanche breakdown therefore produces its own digital output that is captured, along with the digital outputs from all other triggered microcells, by an on-chip counter. The Philips digital SiPM therefore converts digital events (photon detections) directly into a digital photon count. As a result, it is capable of achieving significantly better resolution than conventional SiPMs.

To overcome the ‘dark count’ problem associated with conventional SiPMs, each microcell in the Philips digital SiPM is also equipped with an addressable static memory cell that can be used to disable or enable the microcell. Microcells that show high dark count levels can therefore be prevented from contributing false counts to the SiPM’s output. This facility allows the Philips’ digital SiPM to achieve better signal-to-noise ratios than conventional devices. Because defective microcells in the array can be disabled, it also helps to improve production yield.

Press release: Philips announces breakthrough in fully digital light detection technology...

Technology backgrounder: PHILIPS' FULLY DIGITAL LIGHT DETECTION TECHNOLOGY (.pdf)...

>Dr. Kelly's work demonstrates that the cells can be differentiated with these biomarkers because of the cellular genes that indicate aggressive or benign forms. The scanning electron micrograph illustrates the eight variable structures that the system can repeatably track with less than 5% variation. Analysis time is reported to be 30 minutes as compared with contemporary diagnostics tests which can take days.

The researchers' new device can easily sense the signature biomarkers that indicate the presence of cancer at the cellular level, even though these biomolecules - genes that indicate aggressive or benign forms of the disease and differentiate subtypes of the cancer - are generally present only at low levels in biological samples. Analysis can be completed in 30 minutes, a vast improvement over the existing diagnostic procedures that generally take days.

"Today, it takes a room filled with computers to evaluate a clinically relevant sample of cancer biomarkers and the results aren't quickly available," said Shana Kelley, a professor in the Leslie Dan Faculty of Pharmacy and the Faculty of Medicine, who was a lead investigator on the project and a co-author on the publication.

"Our team was able to measure biomolecules on an electronic chip the size of your fingertip and analyse the sample within half an hour. The instrumentation required for this analysis can be contained within a unit the size of a BlackBerry."

Press release: U of T researchers create microchip that can detect type and severity of cancer...

Nature: Programming nucleic acids detection sensitivity using controlled nanostructuring

University of Toronto: Shana Kelly Lab

(hat tip: Next Big Future)

The Leica TCS SMD Series integrates hardware and software from PicoQuant with the high-end confocal system Leica TCS SP5 II. Researchers can now control a complete SMD experiment via one interface, the LAS AF software from Leica Microsystems. The coordination of different hardware and software components for one SMD experiment is now a thing of the past.

Complex SMD technologies are no longer complicated due to the user-friendly design of the system series. Quick and easy operation is ensured by dedicated application wizards. They guide the user step-by-step through SMD experiments and significantly maximize the reproducibility of data. With the universal SMD raw data format, one and the same data file can be analyzed in various ways and leads to quantification with maximum content.

Press release: All in One: A Single Platform to Study the Dynamics of Cellular Processes ...

Product pages: Leica TCS SMD FCS, TCS SMD FLIM, TCS SMD FLCS

Here's how you operate the Res-Q:

STEP 1 Fill the Res-Q™60 BMC with bone marrow aspirate using a syringe and the supplied clot filter. The needleless port protects the sample from contamination.

STEP 2 Place the Res-Q™60 BMC into a benchtop centrifuge and spin at 3200 rpm for 12 minutes to allow for the separation of the bone marrow components and capturing of the buffy coat into the collection chamber.

STEP 3 Remove device from centrifuge and place on processing tray to re-suspend the buffy coat.

STEP 4 Harvest 6-10 mL of a stem cell rich buffy coat. A 12" sterile line is provided to facilitate transfer of sample back into the surgical field if required.

Press release: THERMOGENESIS ANNOUNCES LAUNCH OF RES-Q SYSTEM...

Product page: Res-Q™60 BMC ...

Res-Q™60 BMC product brochure...

Caltech has released the following statement about SBGN:

SBGN will make it easier for biologists to understand each other's models and share network diagrams more easily, which, Hucka says, has never been more important than in today's era of high-throughput technologies and large-scale network reconstruction efforts. [Michael Hucka is a senior research fellow and codirector of the Biological Network Modeling Center at Caltech's Beckman Institute --ed.] A standard graphical notation will help researchers share this mass of data more efficiently and accurately, which will benefit systems biologists working on a variety of biochemical processes, including gene regulation, metabolism, and cellular signaling.

"Finally, and perhaps most excitingly," adds Hucka, "I believe that, just as happened with the engineering fields, SBGN will act as an enabler for the emergence of new industries devoted to the creation of software tools for working with SBGN, as well as its teaching and publication."

Previous graphical notations in biology have tended to be ambiguous, used in different ways by different researchers, and only suited to specific needs--for example, to represent metabolic networks or signaling pathways. Past efforts to create a more rigid notation failed to become accepted as a standard by the community. Hucka and his collaborators believe that SBGN should be more successful because it represents a more concerted effort to establish a standard by engaging many biologists, modelers, and software-tool developers. In fact, many of those involved in the SBGN effort are the same pioneers who proposed previous notations, demonstrating the degree to which they endorse SBGN as a new standard.

To ensure that this new visual language does not become too vast and complicated, the researchers decided to define three separate types of diagram, which describe molecular process, relationships between entities, and links among biochemical activities. These different types of diagrams complement each other by representing different "views" of the same information, presented in different ways for different purposes, but reusing most of the same graphical symbols. This approach reduces the complexity of any one type of diagram while broadening the range of what can be expressed about a given biological system.

To learn more about SBGN, follow these links:

Abstract in Nature Biotechnology: The Systems Biology Graphical Notation Nature Biotechnology 27, 735 - 741 (2009)

SBGN Project...

Press release: Caltech Scientists Help Launch the First Standard Graphical Notation for Biology...

Flashback: BioModels: a Computational Systems Biology Database

The basics of the technology from Helicos BioSciences:

Within two flow cells, billions of single molecules of sample DNA are captured on an application-specific proprietary surface. These captured strands serve as templates for the sequencing-by-synthesis process:

Polymerase and one fluorescently labeled nucleotide (C, G, A or T) are added.

* The polymerase catalyzes the sequence-specific incorporation of fluorescent nucleotides into nascent complementary strands on all the templates.
* After a wash step, which removes all free nucleotides, the incorporated nucleotides are imaged and their positions recorded.
* The fluorescent group is removed in a highly efficient cleavage process, leaving behind the incorporated nucleotide.
* The process continues through each of the other three bases.
* Multiple four-base cycles result in complementary strands greater than 25 bases in length synthesized on billions of templates—providing a greater than 25-base read from each of those individual templates.

More about the announcement from Ars Technica...

Stanford press release: Professor sequences his entire genome at low cost, with small team...

Article in Nature Biotechnology: Single-molecule sequencing of an individual human genome

Product page: HeliScope™ Single Molecule Sequencer

Flashbacks: Helicos BioSciences Sequences Entire Genome from a Single Molecule of DNA; High Speed Sequencing of Single DNA