From the Department of Engineering at the University of Cambridge:

While current models satisfy the need for precision and reliability, their design falls a long way short in terms of ease of use. They are entirely thumb-operated and are known to cause cases of repetitive strain injury. The students have designed a comfortable, easy-to-use pipette, the Ergopip, which distributes workload to the user's fingers and is just as precise and reliable as existing versions.

The Ergopip...

Full story from The Engineer Online: Students design better pipette...

From ThermoGenesis:

Last month, the Company announced it had submitted a 510(k) pre-market notification application to the FDA. Upon its review, the FDA determined that the device was exempt from the agency’s pre-market notification requirements and will instead be regulated as laboratory equipment labeled for a specific medical use. The device is a derivative of the Company’s AutoXpress™ (AXP™) Platform that is used to volume reduce and collect stem cells from umbilical cord blood.

“This notification that we can immediately begin marketing our MXP device is a major regulatory milestone for the Company and particularly exciting since we received this notification just several weeks after filing our submission, and since it follows by less than a month from having received the CE-Mark enabling us to market the device in the European Community,” noted Dr. William Osgood, Chief Executive Officer.

Press release: THERMOGENESIS ANNOUNCES FDA AUTHORIZATION TO MARKET MARROWXPRESS™ (MXP™) (PDF)

Product page: MarrowXpress...

Flashback: MarrowXpress Stem Cell Processing System Gets CE Mark

Here's what the authors note in the study:

One protein partner is fused to Escherichia coli biotin ligase (BirA), while the other protein partner is fused to BirA’s “acceptor peptide” (AP) substrate. If the two proteins interact, BirA will catalyze site-specific biotinylation of AP, which can be detected by streptavidin staining. To minimize nonspecific signals, we engineered the AP sequence to reduce its intrinsic affinity for BirA. The rapamycin-controlled interaction between FKBP and FRB proteins could be detected in vitro and in cells with a signal to background ratio as high as 28. We also extended the method to imaging of the phosphorylation-dependent interaction between Cdc25C phosphatase and 14-3-3ε phosphoserine/threonine binding protein. Protein−protein interaction detection by proximity biotinylation has the advantages of low background, high sensitivity, small AP tag size, and good spatial resolution in cells.

The following is from a statement issued by MIT:

The new technique allows researchers to tag proteins with probes that link together like puzzle pieces if the proteins interact inside a cell. The probes are derived from an enzyme and its peptide substrate. If the probe-linked proteins interact, the enzyme and substrate also interact, which can be easily detected.

To create the probes, the researchers used the enzyme biotin ligase and its target, a 12-amino-acid peptide.

Their work is conceptually related to an approach that uses GFPs (green fluorescent proteins), which glow when activated, as probes. Half of each GFP molecule is attached to the proteins of interest, and when the proteins interact, the GFP halves fuse and glow. However, this technique results in many false positives, because the GFP halves seek each other out and bind even when the proteins they are attached to are not interacting, said Ting.

The new probes could be used to study nearly any protein-protein interaction, Ting [Alice Ting, MIT Pfizer-Laubach Career Development Assistant Professor of Chemistry] said. The researchers tested their probes on two signaling proteins involved in suppression of the immune system, and on two proteins that play a role in cell division. They are currently using the probe to image the interaction of proteins involved in synapse growth in live neurons.

Press release: New probe may help untangle cells' signaling pathways ...

Abstract: Protein-Protein Interaction Detection in Vitro and in Cells by Proximity Biotinylation J. Am. Chem. Soc., ASAP Article, 10.1021/ja801445p

From the announcement:

In a paper published today [June 27, 2008] titled "The International Embryome Initiative: A Collaborative Database for Navigating the Complexities of Human Embryonic Stem Cell Differentiation," available online at www.futuremedicine.com/loi/rme, BioTime and Embryome Sciences describe the collaboration to map the "embryome" in a manner similar to the international initiatives to map the human DNA or genome in the 1990s. While the database launched today at Embryome.com is currently populated with nearly 2,000 distinct cell types, the complete map will require the collective efforts of hundreds of scientists over the coming months.

The California Institute for Regenerative Medicine, which is the funding arm of the $3 billion California stem cell initiative, has agreed to be the first subscriber to all features of the database on behalf of all researchers residing within the state of California.

Press release: BioTime, Inc. and Embryome Sciences, Inc. Launch Embryome.com and the International Embryome Initiative ...

Embryome.com...

From Sangamo:

Sangamo's ZFNs are designed to permanently modify the DNA sequence encoding CCR5, a co-receptor that enables HIV to enter and infect cells of the immune system. Individuals carrying a naturally occurring mutation of their CCR5 gene, a variant known as CCR5-delta32, have been shown to be resistant to HIV infection.

"The data described in this paper are an important demonstration of the potential therapeutic properties of our product," commented Dale Ando, M.D., Sangamo's vice president of therapeutic development and chief medical officer. "We have demonstrated that a single treatment with our CCR5-specific ZFNs generates a population of HIV-resistant human T-cells similar to the situation in individuals carrying the natural CCR5-delta32 mutation. ZFN-modification of these cells is permanent and makes them resistant to HIV. The modified cells preferentially survive and expand in an animal after HIV infection, providing a reservoir of healthy and uninfectable immune cells. Furthermore, we observed that animals given the ZFN-modified cells had increased numbers of CD4 cells and substantially lower levels of HIV in their blood compared to animals given non-modified cells demonstrating statistically significant protection from the virus. In an HIV-infected patient, such modified cells could be available as a protected reservoir within the immune system to fight both opportunistic infections and HIV itself."

Several major pharmaceutical companies have initiated programs to develop small molecule or monoclonal antibody approaches to block the binding of HIV to CCR5. However, a small molecule or antibody approach requires the constant presence of a sufficiently high concentration of these drugs or antibody to block therapeutically relevant numbers of the CCR5 protein, which is present in thousands of copies on the surface of each T-cell and other tissues in the body. One such drug has been approved by the US Food and Drug Administration with a "black box" warning, the strongest for prescription drugs, concerning the risk of liver toxicity and the possibility of heart attacks.

Sangamo's ZFN technology represents a means of potentially circumventing these limitations or risks by specifically modifying only CD4 T-cells, the principal target of HIV pathology, in a one-time exposure of the cells to ZFNs. This results in permanent modification of the CCR5 protein such that HIV cannot enter and infect the cells. This approach could potentially enable the generation of a reservoir of protected CD4 T-cells that are available to fight the opportunistic infections that are characteristic of AIDS as well as HIV itself. Sangamo expects to initiate a clinical trial to evaluate this approach by the end of the year.

Press release: Sangamo BioSciences Announces Nature Biotechnology Study Demonstrating the Use of Zinc Finger Nucleases to Generate HIV Resistant T Cells ...

Sangamo ZFP technology page...

Abstract in Nature: Establishment of HIV-1 resistance in CD4⁺ T cells by genome editing using zinc-finger nucleases

Each quantum dot was surrounded by a proton sponge that carried a positive charge. Without any quantum dots attached, the siRNA's negative charge would prevent it from penetrating a cell's wall. With the quantum-dot chaperone, the more weakly charged siRNA complex crosses the cellular wall, escapes from the endosome (a fatty bubble that surrounds incoming material) and accumulates in the cellular fluid, where it can do its work disrupting protein manufacture.

Key to the newly published approach is that researchers can adjust the chemical makeup of the quantum dot's proton-sponge coating, allowing the scientists to precisely control how tightly the dots attach to the siRNA.

Quantum dots were dramatically better than existing techniques at stopping gene activity. In experiments, a cell's production of a test protein dropped to 2 percent when siRNA was delivered with quantum dots. By contrast, the test protein was produced at 13 percent to 51 percent of normal levels when the siRNA was delivered with one of three commercial reagents, or reaction-causing substances, now commonly used in laboratories.

Central to the finding is that fluorescent quantum dots allow scientists to watch the siRNA's movements. Previous siRNA trackers gave off light for less than a minute, while quantum dots, developed for imaging, emit light for hours at a time. In the experiments the authors were able to watch the process for many hours to track the gene-silencer's path.

The new approach is also five to 10 times less toxic to the cell than existing chemicals, meaning the quantum dot chaperones are less likely to harm cells. The ideal delivery vehicle would have no effect; the only biological change would be siRNA blocking cells' production of an unwanted protein.

The exact reason that the quantum dots were more effective than previous techniques is, however, still a mystery.

University of Washington press release: Gene silencer and quantum dots reduce protein production to a whisper ...

Abstract: Proton-Sponge Coated Quantum Dots for siRNA Delivery and Intracellular Imaging J. Am. Chem. Soc., ASAP Article, 10.1021/ja800086u

The OMX is based on two main imaging modalities: Structured Illumination and Fast Live 3d Imaging. Here's the explanation from the project page at UCSF:

1) Structured Illumination

Structured illumination microscopy involves illuminating the sample with a pattern caused by interfering beams of light, rather than a single uniform beam. OMX achieves this illumination by passing incident light through a diffraction grating, then recombining the diffracted beams in the sample plane. The emitted light from a sample so illuminated contains normally unobservable high-resolution information that has been shifted into the observable region of frequency space. By acquiring several images of shifted patterns at each Z section, the high-resolution information can be separated and computationally re-shifted to its correct position in frequency space, leading to an overall increase in the resolution of the final reconstructed image.

2) Fast Live 3d Imaging

Although fixed images are a very useful source of information, live imaging is becoming more and more important. Live imaging allows dynamic processes to be directly observed. There are many challenges in live imaging, including bleaching of fluorophores, imaging through tissues, and keeping the sample alive. Images must be acquired quickly, not only so that the process of interest is accurately sampled, but also so that the individual planes of a three-dimensional picture comprise a single timepoint; i.e., temporal spreading of a single image must be minimized. To meet these challenges OMX was designed with very fast cameras and shutters capable of acquiring 100 images per second, a piezoelectric stage that can move very quickly while images are being acquired, and a digital signal processor (DSP) controlling all aspects of image acquisition to ensure precise timing. OMX can acquire separate wavelengths from 4 cameras simultaneously, allowing multiple signals to be detected. Ratio imaging and FRET can also be performed.

More reads: UC Davis press release: New Microscope Is First of Its Kind...;

Applied Precision press release: The World's Most Powerful Commercial Wide-Field Light Microscope Installed at the UC Davis Center for Biophotonics Science and Technology...

OMX project pages at UC Davis and UCSF

The device automatically isolates and concentrates stem cells from bone marrow aspirate in 30 minutes. The entire system runs on a rechargeable NiMH battery. It also includes data tracking software that communicates with the device in real-time. Currently it is only intended for research purposes.

Product page: MarrowXpress...

Press release...

From the press release:

Moving beyond traditional X-ray crystallography systems--where the arrangement of atoms in crystalline material is revealed by analyzing the way X-ray beams are scattered from electrons in the crystal--the energy-recovery linac offers significant advantages. For one, materials subjected to ultrabright X-ray pulses need not be in crystalline form. And the tightly focused beam allows studies at much smaller scales.

As envisioned and invented by experimental physicists at Cornell, energy-recovery linear accelerators produce high-energy, pulsed X-ray beams by injecting electrons into the electromagnetic fields of a series of superconducting microwave cavities in a linear accelerator. Then, in a return loop, the electron beam is turned into X-rays by passing through undulators, which force the beam to oscillate to the right and left of its mean path with horseshoe magnets of alternating orientations. The pulsed X-rays are now ready for studies in multiple stations at the facility.

While the ERL X-ray beam loses about 0.04 percent of its energy during oscillation, 99.98 percent of its remaining energy is recaptured into the electromagnetic fields when the electrons are re-injected into the linac for deceleration--providing energy to accelerate subsequent bunches of electrons.

Compared to a traditional storage-ring X-ray source, such as CHESS, which recycles electrons billions of times but suffers from a compromised beam size, ERLs send each bunch of electrons through the undulators only once. Again and again, ERLs recover and reuse energy that accelerates electron bunches, while maintaining very small beam size--the key to the brilliance needed to study intimate details at the nano-scale.

Full story: Brightest X-ray Vision at the Nano-scale...

Video of Joel Brock of Cornell University, explaining the workings and hopes for the new project.

It consists of a smooth surface that is studded with 250,000 tiny plastic columns measuring only five microns in diameter, rather like a fakir’s bed of nails. These columns are made of elastic polyurethane plastic. When a cell glides across them, it bends them very slightly sideways. This deflection is registered by a digital camera and analyzed by a special software program. The researchers working with project manager Dr. Norbert Danz of the Fraunhofer Institute for Applied Optics and Precision Engineering IOF in Jena have already shown that their ‘Cellforce’ sensor works. It will be the task of initial biological tests to show how different cell types behave. “Analysis of cell locomotion is important for numerous applications,” says Danz. “It could be used to check whether bone cells are successfully populating an implant, or how well a wound is healing.”

Developing the sensor was no easy undertaking. For one thing, the columns have to be coated in such a way that living cells are happy to move across their tips. The cells would otherwise avoid the tips and continue their journey lower down between the columns. In that case, there would be no deflection at all. Danz had the task of adapting the microscope required for cell magnification to make it exactly right for the application. Building the delicate column structure developed by researchers at the Fraunhofer Institute for Manufacturing Engineering and Applied Materials Research IFAM in Bremen is no less tricky: The researchers press liquid plastic at a pressure of 2000 bar into a negative mold and allow it to harden. It is a challenge even to manufacture the required mold, with its 250,000 micron-sized holes. To allow cost-effective production of the ‘Cellforce’ sensor in future, the researchers utilize commercially available plastics and well-established techniques from chip manufacture. The first ‘Cellforce’ prototype is expected to be ready in a year’s time.

Press release: Measuring the footprint of cells ...

Project info page: Development of a single cell based biosensor for subcellular on-line monitoring of cell performance for diagnosis and healthcare...