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New glucokinase activator

Posted in Biochemical pathways, Clinical & Translational, Curation, Diabetes Mellitus, Disease Biology, Enzymes and isoenzymes, Kinase, Metabolism, Pharmaceutical Analytics, Pharmaceutical Drug Discovery, Pharmaceutical Industry Competitive Intelligence, tagged Drug discovery, glucokinase activator on December 15, 2015| Leave a Comment »

New glucokinase activator

Larry H. Bernstein, MD, FCAP, Curator

LPBI

 

RO-28-1675 for Type 2 Diabetes

by DR ANTHONY MELVIN CRASTO Ph.D

http://www.medchemexpress.com/product_pic/hy-10595.gif

 

RO-28-1675

• (2R)-3-Cyclopentyl-2-[4-(methanesulfonyl)phenyl]-N-(thiazol-2-yl)propionamide
• Ro 028-1675
• Ro 0281675
• Ro 28-1675

3-Cyclopentyl-2(R)-[4-(methylsulfonyl)phenyl]-N-(2-thiazolyl)propionamide

MW	378.51		.-70.4 °Conc 0.027 g/100mL; chloroform, 589 nm;  23 °C
Formula	C18H22N2O3S2
CAS No	300353-13-3

Glucokinase Activators

Ro 28-1675 (Ro 0281675) is a potent allosteric GK activator with a SC1.5 value of 0.24± 0.0019 uM.

Roche (Innovator)

Hoffmann La Roche

PHASE 1    Type 2  DIABETES,
IC50 value: 0.24± 0.0019 uM (SC1.5) [1]
Target: Glucokinase activator
The R stereoisomer Ro 28-1675 activated GK with a SC1.5 of 0.24 uM, while the S isomer did not activated GK up to 10 uM. Oral administration of Ro 28-1675 (50 mg/Kg) to male C57B1/6J mice caused a statistically significant reduction in fasting glucose levels and improvement in glucose tolerance relative to the vehicle treated animals [1].
Comparison of rat PK parameters indicated that Ro 28-1675 displayed lower clearance and higher oral bioavailability compared to 9a.

Following a single oral dose, Ro 28-1675 reduced fasting and postprandial glucose levels following an OGTT, was well tolerated, and displayed no adverse effects related to drug administration other than hypoglycemia at the maximum dose (400 mg).

RO-28-1675 as glucokinase activator.

Joseph Grimsby et al., of Roche have recently discovered activators of glucokinase that increase k_cat and decrease the S_0.5 for glucose, and these may offer a treatment for type II diabetes. Glucokinase (GK) plays a key role in whole-body glucose homeostasis by catalyzing the phosphorylation of glucose in cells that express this enzyme, such as pancreatic β cells and hepatocytes.

By screening of a library of 120,000 structurally diverse synthetic compounds, they found one small molecule that increased the enzymatic activity of GK. Chemical optimization of this initial molecule led to the synthesis of RO-28-0450 as a lead GK activator which is a class of antidiabetic agents that act as nonessential, mixed-type GK activators (GKAs) that increase the glucose affinity and maximum velocity (V_max) of GK. RO-28-0450 is a racemic compound.

Activation of GK was exquisitely sensitive to the chirality of the molecule: The R enantiomer, RO-28-1675, was found to be a potent GKA, whereas the S enantiomer, RO-28-1674, was inactive. RO-28-1675 also reversed the inhibitory action of the human glucokinase regulatory protein (GKRP). The activators binding in a glucokinase regulatory site originally was discovered in patients with persistent hyperinsulinemic hypoglycemi.

The result of RO-28-1675 as a potent small molecule GKA may shed light to the chemical biologists to devise strategy for developing activators. Thus for a success to this end we must focus on highly regulated enzymes, or cooperative enzymes such as glucokinase, where nature has provided binding sites that are designed to modulate catalysis.

 

SYNTHESIS

Paper

J. Med. Chem., 2010, 53 (9), pp 3618–3625

DOI: 10.1021/jm100039a

http://pubs.acs.org/doi/abs/10.1021/jm100039a

http://pubs.acs.org/doi/suppl/10.1021/jm100039a/suppl_file/jm100039a_si_001.pdf

Glucokinase (GK) is a glucose sensor that couples glucose metabolism to insulin release. The important role of GK in maintaining glucose homeostasis is illustrated in patients with GK mutations. In this publication, identification of the hit molecule 1 and its SAR development, which led to the discovery of potent allosteric GK activators 9a and21a, is described. Compound 21a (RO0281675) was used to validate the clinical relevance of targeting GK to treat type 2 diabetes.

Flash chromatography (Merck Silica gel 60, 70-230 mesh, 9/1, 3/1, and then 11/9 hexanes/ethyl acetate) afforded (2R)-3-cyclopentyl-2-(4-methanesulfonylphenyl)-N-thiazol-2-yl-propionamide (2.10 g, 74%) as a white foam.   ….

PATENT

WO 2000058293

http://www.google.com/patents/WO2000058293A2?cl=en

 

Discovery, Structure−Activity Relationships, Pharmacokinetics, and Efficacy of Glucokinase Activator (2R)-3-Cyclopentyl-2-(4-methanesulfonylphenyl)-N-thiazol-2-yl-propionamide (RO0281675)

Nancy-Ellen Haynes†, Wendy L. Corbett†, Fred T. Bizzarro†,…., Joseph F. Grippo§, Joseph Grimsby§ and Ramakanth Sarabu*†

J. Med. Chem., 2010, 53 (9), pp 3618–3625   DOI:http://dx.doi.org:/10.1021/jm100039a

Glucokinase (GK) is a glucose sensor that couples glucose metabolism to insulin release. The important role of GK in maintaining glucose homeostasis is illustrated in patients with GK mutations. In this publication, identification of the hit molecule 1 and its SAR development, which led to the discovery of potent allosteric GK activators 9a and 21a, is described. Compound 21a (RO0281675) was used to validate the clinical relevance of targeting GK to treat type 2 diabetes.

REFERENCES

[1]. Haynes NE, et al. Discovery, structure-activity relationships, pharmacokinetics, and efficacy of glucokinase activator (2R)-3-cyclopentyl-2-(4-methanesulfonylphenyl)-N-thiazol-2-yl-propionamide (RO0281675).

Glucokinase (GK) is a glucose sensor that couples glucose metabolism to insulin release. The important role of GK in maintaining glucose homeostasis is illustrated in patients with GK mutations. In this publication, identification of the hit molecule 1 and its SAR development, which led to the discovery of potent allosteric GK activators 9a and 21a, is described. Compound 21a (RO0281675) was used to validate the clinical relevance of targeting GK to treat type 2 diabetes.

http://www.nature.com/nrd/journal/v8/n5/fig_tab/nrd2850_T2.html

NMR…..http://www.medchemexpress.com/product_pdf/HY-10595/Ro%2028-1675-NMR-HY-10595-13569-2014.pdf

http://www.medchemexpress.com/product_pdf/HY-10595/Ro%2028-1675-Lcms_Ms-HY-10595-13569-2014.pdf

J Grimsby et al. Allosteric Activators of Glucokinase: Potential Role in Diabetes Therapy. Science Signaling 2003, 301(5631), 370-373.

T Kietzmann and GK Ganjam. Glucokinase: old enzyme, new target. Exp. Opin. Ther. Patents. 2005, 15(6), 705-713.

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Shortened time for cell renewal

Posted in Bioengineering & reverse engineering design, Biological Networks, Cell Biology, Chemical Biology and its relations to Metabolic Disease, Clinical & Translational, Clinical Genomics, CRISPR/Cas9 & Gene Editing, Curation, tagged CRISPR/Cas9, genetic repair, sequence analysis, skin fibroblast, somatic reprogramming on December 15, 2015| Leave a Comment »

Shortened time for cell renewal

Larry H. Bernstein, MD, FCAP, Curator

LPBI

 

Accelerated Reprogramming and Gene Editing Protocol Can Make Fixed Cells Much Faster

December 14, 2015 by mburatov

https://beyondthedish.wordpress.com/2015/12/14/accelerated-reprogramming-and-gene-editing-protocol-can-make-fixed-cells-much-faster/

Sara Howden and her colleagues at the Morgridge Institute for Research and the Murdoch Children’s Research Institute in Australia have devised a protocol that can significantly decrease the time involved in reprogramming mature adult cells while genetically repairing them at the same time. Such an advance is essential for making future therapies possible.

Howden and others demonstrated that genetically repaired cells can be derived from patient skin cells in as little as two weeks. This is much shorter than the multistep approaches that take more than three months.

How were they able to shorten the time necessary to do this? They combined two integral steps in the procedure. Adult cells were reprogrammed to an embryonic stem cell-like state in order to be differentiated into the cells that we want. Secondly, the cells must undergo gene editing in order to correct the disease-causing mutation.

By in this new protocol developed by Howden and her colleagues, they combined the reprogramming and gene editing steps.

To test their new protocol, Howden and her team used cells isolated from a patient with an inherited retinal degeneration disorder, and an infant with severe immunodeficiency. In both cases, the team not only derived induced pluripotent stem cell lines from the adult cells of these patients, but they were also able to repair the genetic lesion that causes the genetic disease.

This protocol might advance transplant medicine by making gene-correction therapies available to patients in a much timelier fashion and at lower cost.

Presently, making induced pluripotent stem cell lines from a patient’s cells, genetically repairing those cells, expanding them, differentiating them, and then isolating the right cells from transplantation, while checking the cells all along the way and properly characterizing them for safety reasons would take too long and cost too much.

With this new approach, however, Howden and others used the CRISPR/Cas9 technology to edit the damaged genes while reprogramming the cells, greatly reducing the time required to make the cells for transplantation.

Faster reprogramming also decreases the amount of time the cells remain in culture, which minimizes the risks of gene instability or epigenetic changes that can sometimes occur when culturing cells outside the human body.

Howden’s next goal is to adapt her protocol to work with blood cells so that blood samples rather than skin biopsies can be used to secure the cells for reprogramming/gene editing procedure. Blood cells also do not require the expansion that skin cells require, which would even further shorten the time needed to make the desired cell types.

The accelerated pace of the reprogramming procedure could make a genuine difference in those cases where medical interventions are required in as little time as possible. For example, children born with severe combined immunodeficiency usually die within the first few years of life from massive infections.

Howden cautioned, however, that she and her team must first derive a long-term source of blood cells from pluripotent stem cells before such treatments are viable and demonstrate the safety of such treatments as well.

See Stem Cell Reports, 2015: DOI: http://dx.doi.org:/10.1016/j.stemcr.2015.10.009.

 

Simultaneous Reprogramming and Gene Correction of Patient Fibroblasts

Sara E. Howden, John P. Maufort, Bret M. Duffin, Andrew G. Elefanty, Edouard G. Stanley, James A. Thomson

Stem Cell Reports Dec 2015;  5, (6):1109–1118   http://dx.doi.org/10.1016/j.stemcr.2015.10.009

Highlights

• •Episomal reprogramming system is enhanced by expression of miR302/367
• •Gene targeting and reprogramming can be combined in a simple one-step procedure
• •Clonal gene-corrected iPS cell lines can be obtained in as little as 2 weeks

 

Summary

The derivation of genetically modified induced pluripotent stem (iPS) cells typically involves multiple steps, requiring lengthy cell culture periods, drug selection, and several clonal events. We report the generation of gene-targeted iPS cell lines following a single electroporation of patient-specific fibroblasts using episomal-based reprogramming vectors and the Cas9/CRISPR system. Simultaneous reprogramming and gene targeting was tested and achieved in two independent fibroblast lines with targeting efficiencies of up to 8% of the total iPS cell population. We have successfully targeted the DNMT3B and OCT4 genes with a fluorescent reporter and corrected the disease-causing mutation in both patient fibroblast lines: one derived from an adult with retinitis pigmentosa, the other from an infant with severe combined immunodeficiency. This procedure allows the generation of gene-targeted iPS cell lines with only a single clonal event in as little as 2 weeks and without the need for drug selection, thereby facilitating “seamless” single base-pair changes.

Induced pluripotent stem (iPS) cells, generated by introducing defined factors to reprogram terminally differentiated somatic cells, offer enormous potential for the development of autologous or customized cellular therapies to treat or correct many inherited and acquired diseases (Takahashi et al., 2007, Yu et al., 2007). Complications associated with immunorejection can be avoided through the generation and subsequent disease correction of patient-specific iPS cells, which can be differentiated into relevant cell types for the repopulation and regeneration of a defective tissue or organ. Gene targeting by homologous recombination is the ideal approach for the correction of genetic defects as it enables replacement of the defective allele with a normal functional one without disturbing the remaining genome. The generation of a genetically modified iPS cell line typically involved multiple procedures that required the cells to be in culture for an extensive period, drug selection, and several clonal events (Hockemeyer et al., 2009, Howden et al., 2011, Liu et al., 2011, Zou et al., 2011). In the first step, somatic cells are reprogrammed, and several clones are expanded and characterized. Gene targeting constructs are then introduced, and cells are usually subjected to drug selection to isolate and identify correctly modified iPS cell colonies. Once successfully targeted clones are identified, it is preferable to excise the drug selectable marker, commonly flanked by loxP or FRT sites. Taken together, the multiple steps required for the generation of genetically modified iPS cell lines typically require cells to be in culture for several months, which is not compatible for patients for whom urgent medical intervention is imperative. Furthermore, there is evidence to suggest that increased culture times are associated with undesirable changes in genomic integrity, such as duplications of oncogenic genes (Laurent et al., 2011) and other karyotypic abnormalities (Chen et al., 2008). Here we report that reprogramming and gene targeting can be performed together in a one-step procedure that requires only a single electroporation. Multiple gene-targeted iPS cell clones can be generated from patient cells in as little as 2 weeks, requiring only a single clonal event. The procedure also does not require the use of drug selection and permits the generation of clones that contain “seamless” single base-pair changes, without leaving residual loxP or FRT sites in the host genome.

 

Figure 1

Episomal Reprogramming System Is Enhanced with Inclusion of Plasmid Encoding the miR302/367 Cluster

Reprogramming experiments were performed with and without inclusion of the miR302/367 expression plasmid using a normal male fibroblast line. Data represent an average of three independent experiments ± SD.

 

We used an enhanced episomal-based reprogramming system to generate iPS cell lines that would eventually be free of vector sequences. In addition to the seven factors (OCT4, SOX2, NANOG, c-MYC, KLF4, LIN28, and the SV40 Large T-Antigen) encoded by the three oriP-based vectors previously reported to induce pluripotency (Yu et al., 2009), we also forced expression of the micro RNA (miR) 302/367 cluster, which is known to facilitate reprogramming and maintenance of pluripotency (Lin et al., 2008, Miyoshi et al., 2011). The inclusion of an additional episomal vector encoding miR 302/367 resulted in a substantial increase (more than 100-fold) in the total number of iPS cell colonies in human fibroblasts (Figure 1). This plasmid was included in all subsequent reprogramming experiments and was necessary to obtain sufficient iPS cell colony numbers when combining gene targeting and reprogramming in a single step.

…….

We have also successfully used our one-step protocol to simultaneously reprogram and genetically correct the disease-causing mutation in the patient fibroblasts, an autosomal dominant C > T transition in exon 42 of the PRPF8gene. This was achieved using a plasmid encoding the Cas9 protein fromS. pyogenes (Mali et al., 2013b), a plasmid encoding a PRPF8-specific sgRNA that binds 33 bp upstream of the disease-causing mutation, and a 184-bp single-stranded oligodeoxynucleotide (ssODN) (Figure 3A). The ssODN was engineered to contain four synonymous mutations to minimize the possibility of Cas9 protein re-cutting following homologous recombination and to aid in the identification of clones that had undergone a gene-targeting event (Figure 3A). Approximately 3 weeks post-transfection, we randomly isolated and expanded a total of 72 iPS cell colonies for further analysis. A PCR product encoding the region of interest was amplified from the genomic DNA of all 72 clones using primers flanking the target site, which was subsequently analyzed by Sanger sequencing. Cas9-induced modification of one or both PRPF8 alleles was observed in 22 (31%) of the clones analyzed, most commonly detected as a nonhomologous end joining (NHEJ) event within the intended cut site. Homologous recombination at the target site could be detected in 6 (8%) clones, as evidenced by the loss of the disease-causing mutation or the presence of one or more synonymous mutations carried by the corrective ssODN (Table 1). Genetic correction of the autosomal dominant patient-specific mutation was observed in 2 clones, while targeting of the wild-type allele was observed in 4 clones. We were unable to determine which allele had undergone gene targeting in 1 clone (P.57) due to a 151-bp deletion spanning the site of the mutation. Surprisingly, 1 clone (P.50) appeared to have undergone bi-allelic homologous recombination, as evidenced by correction of the patient-specific mutation and the presence of ssODN-specific synonymous mutations on both alleles (Figures 3B and 3C). However, this clone also contained a 1-bp deletion approximately 50 bp upstream of the intended site of the Cas9-induced double-stranded break. We hypothesize that this is most likely due to homologous recombination with an incorrectly synthesized ssODN rather than an additional mutation caused by NHEJ, which normally occurs at the site of the double-stranded break.

 

Table 1Analysis of Gene-Targeted iPS Cell Clones Derived from Patient with Retinitis Pigmentosa

Clone	Modification Observed at PRPF8 Target Site (Exon 42)
P.16	no correction of mutation but presence of SM1 and SM2 on mutant allele; wild-type allele unmodified
P.50	one allele contains SMs 1–3; other allele contains SMs 1–4 and 1-bp deletion ≈30 bp upstream of Cas9 target site
P.57	one allele contains SMs 1–3; other allele contains 151-bp deletion (spanning 124 bp downstream and 7 bp upstream of Cas9 target site) and 105-bp insertion
P.71	correction of mutant allele, but no SMs present; wild-type allele has a 2-bp insertion within Cas9 target site
P.72	wild-type allele contains SMs 1–4; mutant allele has 1-bp deletion
P.73	wild-type allele contains SMs 1–3; mutant allele has 2-bp deletion within Cas9 target site

SM, synonymous mutation.

 

http://www.cell.com/cms/attachment/2040890164/2054788036/gr3.jpg

Figure 3

Simultaneous Reprogramming and Genetic Correction of thePRPF8 Gene in Fibroblasts from a Patient with Retinitis Pigmentosa

(A) Schematic diagram of the PRPF8 gene, with mutation in exon 42. The Cas9 target site (red), the patient-specific mutation (blue), and antisense single-stranded DNA template used for gene repair are shown.

(B) Sequencing analysis of exon 42 of the PRPF8 gene in the genomic DNA from uncorrected patient-specific iPS cells. Both wild-type and mutant alleles are shown.

(C) Sequencing analysis of genomic DNA from a single iPS cell clone following successful simultaneous reprogramming and genetic correction of patient-specific fibroblasts. Both alleles appear to have undergone homologous recombination with the corrective ssODN as evidenced by the presence of the ssODN-specific synonymous mutations (SM 1-4) on both alleles. One allele also has a single base-pair deletion, which is most likely caused by an ssODN that was incorrectly synthesized. The location of the patient-specific mutation and synonymous mutations introduced by the repair ssODN are marked by black boxes.

 

Next we attempted to correct the disease-causing mutation in a fibroblast line isolated from an infant with severe combined immunodeficiency (SCID), caused by mutations in the gene encoding adenosine deaminase (ADA). SCID patients could particularly benefit from a one-step protocol that facilitates the expedited generation of gene-corrected iPS cells because without early intervention, such as a bone marrow transplant, patients typically die within the first 1 to 2 years of life. We first attempted to simultaneously reprogram and target DNMT3B in ADA-SCID fibroblasts and identified one EGFP-expressing colony (0.9%) out of a total of 108 iPS cell colonies (Figure S2). PCR analysis confirmed targeting of theDNMT3B locus (see Figure 2E). We next attempted to simultaneously reprogram and correct one of the disease-causing mutations in the ADA-SCID fibroblasts using our one-step protocol. The fibroblasts were derived from a patient who is a compound heterozygote: one allele has a C > T transition in exon 11 of the ADAgene (1,081C > T), and the second allele has an A > G transition in the 3-prime splice site of intron 3, resulting in a deletion of exon 4 from mature mRNA. We chose to correct the C > T transition in exon 11 using an sgRNA specific to the mutant, but not wild-type, exon 11 sequence of the ADA gene (Figure 4A). We hypothesized that this would minimize Cas9 cutting in both alleles, as seen in the majority of the PRPF8 gene-targeted iPS cell lines, where only 1 out of the 6 clones did not have a second allele modified, either by NHEJ or a second homologous recombination event. To facilitate gene correction we used a 175-bp single-stranded corrective ssODN, which was engineered to contain a single synonymous mutation within the Cas9 target site (Figure 4A). A total of 55 colonies were expanded and screened, with Cas9-induced modification of ADAexon 11 observed in 20 (36%) clones, as determined by Sanger sequencing of a 1.4-kb PCR product amplified from genomic DNA using primers flanking the target site. Gene targeting was detected in 3 (5%) clones, as evidenced by the loss of the disease-causing mutation and the presence of the synonymous mutation carried by the corrective ssODN. Genetic correction of the patient-specific mutation in exon 11 was observed in all three clones, without modification of the second allele, indicating that Cas9 preferentially favored the mutant exon 11 sequence (over wild-type). ……

 

http://www.cell.com/cms/attachment/2040890164/2054788039/gr4.jpg

Figure 4

Simultaneous Reprogramming and Genetic Correction of ADA-SCID Fibroblasts

(A) Schematic diagram of the ADA gene, with mutation in exon 11. The Cas9 target site (red), the patient-specific mutation (blue), and antisense single-stranded DNA template used for gene repair are shown.

(B) Sequencing analysis of exon 11 of the ADA gene in the genomic DNA of an uncorrected and two gene-corrected iPS cell lines derived from ADA-SCID fibroblasts. One of the gene-corrected lines (clone Bb) was also found to carry a G > A transition approximately 35 bp downstream of the intended DNA double-stranded break, and most likely introduced by an incorrectly synthesized ssODN.

(C) Sequencing analysis of the ADA transcript amplified from the cDNA of an uncorrected and two gene-corrected iPS cell lines. The location of the patient-specific mutation, synonymous mutation, and G > A transition introduced by the repair ssODN are marked by black boxes.

……….

 

We have demonstrated the feasibility of performing reprogramming and gene correction together in a simple one-step procedure that enables the generation of multiple gene-corrected and uncorrected iPS cell lines in as little as 2 weeks, requiring considerably less time and resources compared to conventional multi-step protocols that can take several months to complete. In a therapeutic context this should facilitate transplantation medicine by making gene-corrected cells available to patients in a more timely manner, while potentially minimizing the risks associated with extended cell culture, drug selection, and multiple clonal events. In addition, we anticipate that comparisons between corrected and matched uncorrected control iPS cell lines generated from a single experiment will also be extremely useful for disease modeling and understanding the underlying molecular mechanisms governing disease, because any observed differences between corrected and uncorrected cells can be attributed to the patient-specific mutation rather than differences in genetic background.

However, it is important to note that a number of studies have demonstrated that iPS cell lines derived from skin biopsies typically harbor a unique subset of de novo genetic abnormalities, either in the form of copy-number variation or single base-pair changes (Abyzov et al., 2012, Gore et al., 2011) and that iPS cell lines generated from the same parental line can vary significantly with respect to whole-genome gene expression in the differentiated state (Reinhardt et al., 2013). Nonetheless, it is reasonable to expect that the confounding effects arising from the variations that exist across different iPS cell clones may be minimized by comparing multiple gene-corrected or gene-targeted clones with multiple uncorrected clones. In this regard a consistent difference that is observed exclusively in the corrected versus uncorrected lines can most likely be attributed to the patient-specific mutation rather than variations that may exist from one clone to the next. In the current study we routinely observed targeting efficiencies of > 5%, enabling the generation of multiple gene-targeted and “matched” uncorrected clones from a single experiment.

 

 

 

 

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Hybrid lipid bioelectronic membranes

Posted in Bioengineering & reverse engineering design, BioTechnology - Venture Creation, Cell Biology, Signaling & Cell Circuits, Curation, Electrophysiology, Innovations, Innovations in Neurophysiology & Neuropsychology, Ionic Transporters Na+, Lipid metabolism, Lipidomics, Lipids, Liposome, Metabolism, Microvesicle, Na-K transport, Nephrology, Neurohumoral Transmission, Physics, Proteins, Proteomics, Signaling, Signaling & Cell Circuits, Synaptic vesicle, tagged bioengineering, Biological sciences, Biophysics, Biotechnology, ion transport, lipid bilayers on December 14, 2015| Leave a Comment »

Hybrid lipid bioelectronic membranes

Larry H. Bernstein, MD, FCAP, Curator

LPBI

 

Hybrid solid-state chips and biological cells integrated at molecular level

Biological ion channels combine with solid-state transistors to create a new kind of hybrid bioelectronics. Imagine chips with dog-like capability to taste and smell, or even recognize specific molecules.
http://www.kurzweilai.net/hybrid-solid-state-chips-and-biological-cells-integrated-at-molecular-level

http://www.kurzweilai.net/images/biocell-CMOS-.jpg

Illustration depicting a biocell attached to a CMOS integrated circuit with a membrane containing sodium-potassium pumps in pores. Energy is stored chemically in ATP molecules. When the energy is released as charged ions (which are then converted to electrons to power the chip at the bottom of the experimental device), the ATP is converted to ADP + inorganic phosphate. (credit: Trevor Finney and Jared Roseman/Columbia Engineering)

Columbia Engineering researchers have combined biological and solid-state components for the first time, opening the door to creating entirely new artificial biosystems.

In this experiment, they used a biological cell to power a conventional solid-state complementary metal-oxide-semiconductor (CMOS) integrated circuit. An artificial lipid bilayer membrane containing adenosine triphosphate (ATP)-powered ion pumps (which provide energy for cells) was used as a source of ions (which were converted to electrons to power the chip).

The study, led by Ken Shepard, Lau Family Professor of Electrical Engineering and professor of biomedical engineering at Columbia Engineering, was published online today (Dec. 7, 2015) in an open-access paper in Nature Communications.

How to build a hybrid biochip

Living systems achieve this functionality with their own version of electronics based on lipid membranes and ion channels and pumps, which act as a kind of “biological transistor.” Charge in the form of ions carry energy and information, and ion channels control the flow of ions across cell membranes.

Solid-state systems, such as those in computers and communication devices, use electrons; their electronic signaling and power are controlled by field-effect transistors.

To build a prototype of their hybrid system, Shepard’s team packaged a CMOS integrated circuit (IC) with an ATP-harvesting “biocell.” In the presence of ATP, the system pumped ions across the membrane, producing an electrical potential (voltage)* that was harvested by the integrated circuit.

“We made a macroscale version of this system, at the scale of several millimeters, to see if it worked,” Shepard notes. “Our results provide new insight into a generalized circuit model, enabling us to determine the conditions to maximize the efficiency of harnessing chemical energy through the action of these ion pumps. We will now be looking at how to scale the system down.”

While other groups have harvested energy from living systems, Shepard and his team are exploring how to do this at the molecular level, isolating just the desired function and interfacing this with electronics. “We don’t need the whole cell,” he explains. “We just grab the component of the cell that’s doing what we want. For this project, we isolated the ATPases because they were the proteins that allowed us to extract energy from ATP.”

The capability of a bomb-sniffing dog, no Alpo required

Next, the researchers plan to go much further, such as recognizing specific molecules and giving chips the potential to taste and smell.

The ability to build a system that combines the power of solid-state electronics with the capabilities of biological components has great promise, they believe. “You need a bomb-sniffing dog now, but if you can take just the part of the dog that is useful — the molecules that are doing the sensing — we wouldn’t need the whole animal,” says Shepard.

The technology could also provide a power source for implanted electronic devices in ATP-rich environments such as inside living cells, the researchers suggest.

*  “In general, integrated circuits, even when operated at the point of minimum energy in subthreshold, consume on the order of 10⁻² W mm⁻² (or assuming a typical silicon chip thickness of 250 μm, 4 × 10⁻² W mm⁻³). Typical cells, in contrast, consume on the order of 4 × 10⁻⁶ W mm⁻³. In the experiment, a typical active power dissipation for the IC circuit was 92.3 nW, and the active average harvesting power was 71.4 fW for the biocell (the discrepancy is managed through duty-cycled operation of the IC).” — Jared M. Roseman et al./Nature Communications

 

references:

Jared M. Roseman et al. Hybrid integrated biological–solid-state system powered with adenosine triphosphate. Nature Communications 6, 10070 doi:10.1038/ncomms10070. 07 December 2015 (open access)

Topics: Biotech | Electronics | Synthetic Biology

Hybrid integrated biological–solid-state system powered with adenosine triphosphate

Jared M. Roseman, Jianxun Lin, Siddharth Ramakrishnan, Jacob K. Rosenstein & Kenneth L. Shepard
Nature Communications 7 Dec 2015; 6(10070)     http://dx.doi.org:/10.1038/ncomms10070

There is enormous potential in combining the capabilities of the biological and the solid state to create hybrid engineered systems. While there have been recent efforts to harness power from naturally occurring potentials in living systems in plants and animals to power complementary metal-oxide-semiconductor integrated circuits, here we report the first successful effort to isolate the energetics of an electrogenic ion pump in an engineered in vitro environment to power such an artificial system. An integrated circuit is powered by adenosine triphosphate through the action of Na⁺/K⁺ adenosine triphosphatases in an integrated in vitro lipid bilayer membrane. The ion pumps (active in the membrane at numbers exceeding 2 × 10⁶ mm⁻²) are able to sustain a short-circuit current of 32.6 pA mm⁻² and an open-circuit voltage of 78 mV, providing for a maximum power transfer of 1.27 pW mm⁻² from a single bilayer. Two series-stacked bilayers provide a voltage sufficient to operate an integrated circuit with a conversion efficiency of chemical to electrical energy of 14.9%.

 

Figure 1: Fully hybrid biological–solid-state system.

 

 

http://www.nature.com/ncomms/2015/151207/ncomms10070/images/ncomms10070-f1.jpg

(a) Illustration depicting biocell attached to CMOS integrated circuit. (b) Illustration of membrane in pore containing sodium–potassium pumps. (c) Circuit model of equivalent stacked membranes, =2.1 pA, =98.6 GΩ, =575 GΩ and =75 pF, Ag/AgCl electrode equivalent resistance R_WE+R_CE<20 kΩ, energy-harvesting capacitor C_STOR=100 nF combined with switch as an impedance transformation network (only one switch necessary due to small duty cycle), and CMOS IC voltage doubler and resistor representing digital switching load. R_L represents the four independent ring oscillator loads. (d) Equivalent circuit detail of stacked biocell. (e) Switched-capacitor voltage doubler circuit schematic.

 

The energetics of living systems are based on electrochemical membrane potentials that are present in cell plasma membranes, the inner membrane of mitochondria, or the thylakoid membrane of chloroplasts¹. In the latter two cases, the specific membrane potential is known as the proton-motive force and is used by proton adenosine triphosphate (ATP) synthases to produce ATP. In the former case, Na⁺/K⁺-ATPases hydrolyse ATP to maintain the resting potential in most cells.

While there have been recent efforts to harness power from some naturally occurring potentials in living systems that are the result of ion pump action both in plants² and animals^{3, 4} to power complementary metal-oxide semiconductor (CMOS) integrated circuits (ICs), this work is the first successful effort to isolate the energetics of an electrogenic ion pump in an engineered in vitroenvironment to power such an artificial system. Prior efforts to harness power from in vitromembrane systems incorporating ion-pumping ATPases^{5, 6, 7, 8, 9} and light-activated bacteriorhodopsin^{9, 10, 11} have been limited by difficulty in incorporating these proteins in sufficient quantity to attain measurable current and in achieving sufficiently large membrane resistances to harness these currents. Both problems are solved in this effort to power an IC from ATP in an in vitro environment. The resulting measurements provide new insight into a generalized circuit model, which allows us to determine the conditions to maximize the efficiency of harnessing chemical energy through the action of electrogenic ion pumps.

 

ATP-powered IC

Figure 1a shows the complete hybrid integrated system, consisting of a CMOS IC packaged with an ATP-harvesting ‘biocell’. The biocell consists of two series-stacked ATPase bearing suspended lipid bilayers with a fluid chamber directly on top of the IC. Series stacking of two membranes is necessary to provide the required start-up voltage for IC and eliminates the need for an external energy source, which is typically required to start circuits from low-voltage supplies^{2, 3}. As shown inFig. 1c, a matching network in the form of a switched capacitor allows the load resistance of the IC to be matched to that presented by the biocell. In principle, the switch S can be implicit. The biocell charges C_STOR until the self start-up voltage, V_start, is reached. The chip then operates until the biocell voltage drops below the minimum supply voltage for operation, V_min. Active current draw from the IC stops at this point, allowing the charge to build up again on C_STOR. In our case, however, the IC leakage current exceeds 13.5 nA at V_start, more than can be provided by the biocell. As a result, an explicit transistor switch and comparator (outside of the IC) are used for this function in the experimental results presented here, which are not powered by the biocell and not included in energy efficiency calculations (see Supplementary Discussion for additional details). The energy from the biocell is used to operate a voltage converter (voltage doubler) and some simple inverter-based ring oscillators in the IC, which receive power from no other sources.

http://www.nature.com/ncomms/2015/151207/ncomms10070/images/ncomms10070-f1.jpg

 

……..   Prior to the addition of ATP, the membrane produces no electrical power and has an R_m of 280 GΩ. A 1.7-pA short-circuit (SC) current (Fig. 2b) through the membrane is observed upon the addition of ATP (final concentration 3 mM) to the cis chamber where functional, properly oriented enzymes generate a net electrogenic pump current. To perform these measurements, currents through each membrane of the biocell are measured using a voltage-clamp amplifier (inset of Fig. 2b) with a gain of 500 GΩ with special efforts taken to compensate amplifier leakage currents. Each ATPase transports three Na⁺ ions from the cis chamber to the trans chamber and two K⁺ ions from thetrans chamber to the cis chamber (a net charge movement of one cation) for every molecule of ATP hydrolysed. At a rate of 100 hydrolysis events per second under zero electrical (SC) bias¹³, this results in an electrogenic current of ~16 aA. The observed SC current corresponds to about 10⁵ active ATPases in the membrane or a concentration of about 2 × 10⁶ mm⁻², about 5% of the density of channels occurring naturally in mammalian nerve fibres¹⁴. It is expected that half of the channels inserted are inactive because they are oriented incorrectly.

Figure 2: Single-cell biocell characterization.

http://www.nature.com/ncomms/2015/151207/ncomms10070/images_article/ncomms10070-f2.jpg

(a)…Pre-ATP data linear fit (black line) slope yield R_m=280 GΩ. Post ATP data fit to a Boltzmann curve, slope=0.02 V (blue line). Post-ATP linear fit (red line) yields I_p=−1.8 pA and R_p=61.6 GΩ, which corresponds to a per-ATP source resistance of 6.16 × 10¹⁵. The current due to membrane leakage through R_{m} is subtracted in the post-ATP curve…. (b)…

 

Current–voltage characteristics of the ATPases

Figure 2a shows the complete measured current–voltage (I–V) characteristic of a single ATPase-bearing membrane in the presence of ATP. The current due to membrane leakage through R_m is subtracted in the post-ATP curve. The I–V characteristic fits a Boltzmann sigmoid curve, consistent with sodium–potassium pump currents measured on membrane patches at similar buffer conditions^{13, 15, 16}. This nonlinear behaviour reflects the fact that the full ATPase transport cycle (three Na⁺ ions from cis to trans and two K⁺ ions from trans to cis) time increases (the turn-over rate, k_ATP, decreases) as the membrane potential increases¹⁶. No effect on pump current is expected from any ion concentration gradients produced by the action of the ATPases (seeSupplementary Discussion). Using this Boltzmann fit, we can model the biocell as a nonlinear voltage-controlled current source I_ATPase (inset Fig. 2a), in which the current produced by this source varies as a function of V_m. In the fourth quadrant, where the cell is producing electrical power, this model can be linearized as a Norton equivalent circuit, consisting of a DC current source (I_p) in parallel with a current-limiting resistor (R_p), which acts to limit the current delivered to the load at increasing bias (I_ATPase~I_p−V_m/R_p). Figure 2c shows the measured and simulated charging of C_m for a single membrane (open-circuited voltage). A custom amplifier with input resistance R_in>10 TΩ was required for this measurement (see Electrical Measurement Methods).

 

Reconciling operating voltage differences

The electrical characteristics of biological systems and solid-state systems are mismatched in their operating voltages. The minimum operating voltage of solid-state systems is determined by the need for transistors to modulate a Maxwell–Boltzmann (MB) distribution of carriers by several orders of magnitude through the application of a potential that is several multiples of kT/q (where kis Boltzmann’s constant, T is the temperature in degrees Kelvin and q is the elementary charge). Biological systems, while operating under the same MB statistics, have no such constraints for operating ion channels since they are controlled by mechanical (or other conformational) processes rather than through modulation of a potential barrier. To bridge this operating voltage mismatch, the circuit includes a switched-capacitor voltage doubler (Fig. 1d) that is capable of self-startup from voltages as low V_start=145 mV (~5.5 kT/q) and can be operated continuously from input voltages from as low as V_min=110 mV (see Supplementary Discussion)…..

 

Maximizing the efficiency of harvesting energy from ATP

Solid-state systems and biological systems are also mismatched in their operating impedances. In our case, the biocell presents a source impedance, =84.2 GΩ, while the load impedance presented by the complete integrated circuit (including both the voltage converter and ring oscillator loads) is approximately R_IC=200 kΩ. (The load impedance, R_L, of the ring oscillators alone is 305 kΩ.) This mismatch in source and load impedance is manifest in large differences in power densities. In general, integrated circuits, even when operated at the point of minimum energy in subthreshold, consume on the order of 10⁻² W mm⁻² (or assuming a typical silicon chip thickness of 250 μm, 4 × 10⁻² W mm⁻³) (ref. 17). Typical cells, in contrast, consume on the order of 4 × 10⁻⁶ W mm⁻³ (ref. 18). In our case, a typical active power dissipation for our circuit is 92.3 nW, and the active average harvesting power is 71.4 fW for the biocell. This discrepancy is managed through duty-cycled operation of the IC in which the circuit is largely disabled for long periods of time (T_charge), integrating up the power onto a storage capacitor (C_STOR), which is then expended in a very brief period of activity (T_run), as shown in Fig. 3a.

The overall efficiency of the system in converting chemical energy to the energy consumed in the load ring oscillator (η) is given by the product of the conversion efficiency of the voltage doubler (η_converter) and the conversion efficiency of chemical energy to electrical energy in the biocell (η_biocell), η=η_converter × η_biocell. η_converter is relatively constant over the range of input voltages at ~59%, as determined by various loading test circuits included in the chip design (Supplementary Figs 1–6). η_biocell, however, varies with transmembrane potential V_m. η is the efficiency in transferring power to the power ring oscillator loads from the ATP harvested by biocell.

…….

To first order, the energy made available to the Na⁺/K⁺-ATPase by the hydrolysis of ATP is independent of the chemical or electric potential of the membrane and is given by |ΔG_ATP|/(qN_A), where ΔG_ATP is the Gibbs free energy change due to the ATP hydrolysis reaction per mole of ATP at given buffer conditions and N_A is Avogadro’s number. Since every charge that passes through I_ATPase corresponds to a single hydrolysis event, we can use two voltage sources in series with I_ATPase to independently account for the energy expended by the pumps both in moving charge across the electric potential difference and in moving ions across the chemical potential difference. The dependent voltage source V_loss in this branch fixes the voltage across I_ATPase, and the total power produced by the pump current source is (|ΔG_ATP|/N_A)(Nk_ATP), which is the product of the energy released per molecule of ATP, the number of active ATPases and the ATP turnover rate. The power dissipated in voltage source V_chem models the work performed by the ATPases in transporting ions against a concentration gradient. In the case of the Na⁺/K⁺ ATPase,V_chem is given by . The power dissipated in this source is introduced back into the circuit in the power generated by the Nernst independent voltage sources, and . The power dissipated in the dependent voltage source V_loss models any additional power not used to perform chemical or electrical work. ……

 

Integration of ATP-harvesting ion pumps could provide a means to power future CMOS microsystems scaled to the level of individual cells²². In molecular diagnostics, the integration of pore-forming proteins such as alpha haemolysin²³ or MspA porin²⁴ with CMOS electronics is already finding application in DNA sequencing²⁵. Exploiting the large diversity of function available in transmembrane proteins in these hybrid systems could, for example, lead to highly specific sensing platforms for airborne odorants or soluble molecular entities^{26, 27}. Heavily multiplexed platforms could become high-throughput in vitro drug-screening platforms against this diversity of function. In addition, integration of transmembrane proteins with CMOS may become a convenient alternative to fluorescence for coupling to synthetic biological systems²⁸.

 

Roseman, J. M. et al. Hybrid integrated biological–solid-state system powered with adenosine triphosphate. Nat. Commun. 6:10070      http://dx.doi.org:/10.1038/ncomms10070 (2015).

 

 

• Rottenberg, H. The measurement of membrane potential and deltapH in cells, organelles, and vesicles. Methods Enzymol. 55, 547–569 (1979).
  • CAS
  • PubMed
  • Show context
• Himes, C., Carlson, E., Ricchiuti, R. J., Otis, B. P. & Parviz, B. A. Ultralow voltage nanoelectronics powered directly, and solely, from a tree. IEEE Trans. Nanotechnol. 9, 2–5(2010).
  • Article
  • Show context
• Mercier, P. P., Lysaght, A. C., Bandyopadhyay, S., Chandrakasan, A. P. & Stankovic, K. M.Energy extraction from the biologic battery in the inner ear. Nat. Biotechnol. 30, 1240–1243(2012).
  • CAS
  • ISI
  • PubMed
  • Article
  • Show context
• Halámková, L. et al. Implanted Biofuel Cell Operating in a Living Snail. J. Am. Chem. Soc.134, 5040–5043 (2012).
  • CAS
  • PubMed
  • Article
  • Show context

 

 

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N3xt generation carbon nanotubes

Posted in Artificial Intelligence - Breakthroughs in Theories and Technologies, BioIT: BioInformatics, Computational Biology/Systems and Bioinformatics, Curation, Electronic Health Record, Innovations, tagged amorphous oxide semiconductor zinc–tin-oxide (ZTO), carbon nanotubes, electronic engineering, high performance transistors, Memristor, Nano-Engineered Computing Systems Technology (N3XT), resistive random access memory (RRAM), Resistive switching on December 14, 2015| Leave a Comment »

N3xt generation carbon nanotubes

Larry H. Bernstein, MD, FCAP, Curator

LPBI

 

Skyscraper-style carbon-nanotube chip design ‘boosts electronic performance by factor of a thousand’

http://www.kurzweilai.net/skyscraper-style-carbon-nanotube-chip-design-boosts-electronic-performance-by-factor-of-a-thousand

 

 

http://www.kurzweilai.net/images/computing-high-rise-architecture.jpg

A new revolutionary high-rise architecture for computing (credit: Stanford University)

 

Researchers at Stanford and three other universities are creating a revolutionary new skyscraper-like high-rise architecture for computing based on carbon nanotube materials instead of silicon.

In Rebooting Computing, a special issue (in press) of the IEEE Computer journal, the team describes its new approach as “Nano-Engineered Computing Systems Technology,” or N3XT.

Suburban-style chip layouts create long commutes and regular traffic jams in electronic circuits, wasting time and energy, they note.

N3XT will break data bottlenecks by integrating processors and memory-like floors in a skyscraper and by connecting these components with millions of “vias,” which play the role of tiny electronic elevators.

The N3XT high-rise approach will move more data, much faster, using far less energy, than would be possible using low-rise circuits, according to the researchers.

Stanford researchers including Associate Professor Subhasish Mitra and Professor H.-S. Philip Wong have “assembled a group of top thinkers and advanced technologies to create a platform that can meet the computing demands of the future,” Mitra says.

“When you combine higher speed with lower energy use, N3XT systems outperform conventional approaches by a factor of a thousand,” Wong claims.

Carbon nanotube transistors

Engineers have previously tried to stack silicon chips but with limited success, the researchers suggest. Fabricating a silicon chip requires temperatures close to 1,800 degrees Fahrenheit, making it extremely challenging to build a silicon chip atop another without damaging the first layer. The current approach to what are called 3-D, or stacked, chips is to construct two silicon chips separately, then stack them and connect them with a few thousand wires.

But conventional 3-D silicon chips are still prone to traffic jams and it takes a lot of energy to push data through what are a relatively few connecting wires.

The N3XT team is taking a radically different approach: building layers of processors and memory directly atop one another, connected by millions of vias that can move more data over shorter distances that traditional wire, using less energy, and immersing computation and memory storage into an electronic super-device.

The key is the use of non-silicon materials that can be fabricated at much lower temperatures than silicon, so that processors can be built on top of memory without the new layer damaging the layer below. As in IBM’s recent chip breakthrough (see “Method to replace silicon with carbon nanotubes developed by IBM Research“), N3XT chips are based on carbon nanotube transistors.

Transistors are fundamental units of a computer processor, the tiny on-off switches that create digital zeroes and ones. CNTs are faster and more energy-efficient than silicon processors, and much thinner. Moreover, in the N3XT architecture, they can be fabricated and placed over and below other layers of memory.

Among the N3XT scholars working at this nexus of computation and memory are Christos Kozyrakis and Eric Pop of Stanford, Jeffrey Bokor and Jan Rabaey of the University of California, Berkeley, Igor Markov of the University of Michigan, and Franz Franchetti and Larry Pileggi of Carnegie Mellon University.

New storage technologies 

Team members also envision using data storage technologies that rely on materials other than silicon. This would allow for the new materials to be manufactured on top of CNTs, using low-temperature fabrication processes.

One such data storage technology is called resistive random-access memory, or RRAM (see “‘Memristors’ based on transparent electronics offer technology of the future“). Resistance slows down electrons, creating a zero, while conductivity allows electrons to flow, creating a one. Tiny jolts of electricity switch RRAM memory cells between these two digital states. N3XT team members are also experimenting with a variety of nanoscale magnetic storage materials.

Just as skyscrapers have ventilation systems, N3XT high-rise chip designs incorporate thermal cooling layers. This work, led by Stanford mechanical engineers Kenneth Goodson and Mehdi Asheghi, ensures that the heat rising from the stacked layers of electronics does not degrade overall system performance.

Mitra and Wong have already demonstrated a working prototype of a high-rise chip. At the International Electron Devices Meeting in December 2014 they unveiled a four-layered chip made up of two layers of RRAM memory sandwiched between two layers of CNTs (see “Stanford engineers invent radical ‘high-rise’ 3D chips“).

In their N3XT paper they ran simulations showing how their high-rise approach was a thousand times more efficient in carrying out many important and highly demanding industrial software applications.

 

 

references:

• M. Aly, M. Gao, G. Hills, C-S Lee, G. Pitner, M. Shulaker, T. Wu, M. Asheghi, J. Bokor, F. Franchetti, K. Goodson, C. Kozyrakis, I. Markov, K. Olukotun, L. Pileggi, E. Pop, J. Rabaey, C. Ré, H.-S.P. Wong and S. Mitra, Energy-Efficient Abundant-Data Computing: The N3XT 1,000X. IEEE Computer, Special Issue on Rebooting Computing, Dec. 2015 (in press)

Topics: Computers/Infotech/UI | Electronics | Nanotech/Materials Science

This is a little off-thread, but it does involve carbon, so this is the only place I can squeeze this prediction in…
The big news tonight is that the lithium batteries in electric skate boards called “hoverboards” are catching on fire.
This is going to take a lot of them off of the market. But…they will rise again when carbon batteries with graphene and CNTs and boron nitride and I don’t know what else make batteries run as cool as these high-rise CNT chips.
In fact, these high-rise CNT chips will most likely be part of the power control and distribution in the N3XT generation of hoverboards.

 

I am really curious what will be the next computing paradigm. Personally, I see more than one type of computers being used at the same time : neuromorphic, optical, electronic von Neumann nanotube transistors 3D chips, quantum for some purposes and also magnetic storage (memristors).
What is even more interesting, Mr Kurzweil wrote and said that nanotube high-rise computers like described in the article here will be dominant type of computers in the 20s. It may or may not be true.

 

Oh for sure, Kynareth, the first von Neumann machines will do their work with these processors. But memristors should also be a part of them.
I suspect that high-rise cnt chips will indeed be dominant as soon as they come to market. This will give you the N3XT “Field of Dreams.”
If you build it they will come. As soon as it is produced in mass quantities, everybody will come and beat down the doors to get them.

 

This is fantastic. I want the next, or the third next gen of this to be a molecularly built up block of circuitry. This article shows advances using the nano-tube connector that has been experimented before, and also the replacement overall in the circuitry. I only suggest that further generation because it resembles the “molybloc circuits”-bricks and tiles of densely packed circuitry, molybloc standing for molecular block circuitry, found in the Honor Harringoton Sci Fi series (David Weber).

 

Stanford engineers invent radical ‘high-rise’ 3D chips

http://www.kurzweilai.net/stanford-engineers-invent-radical-high-rise-3d-chips

http://www.kurzweilai.net/images/high-rise-chip.jpg

A four-layer prototype high-rise chip built by Stanford engineers. The bottom and top layers are logic transistors. Sandwiched between them are two layers of memory. The vertical tubes are nanoscale electronic “elevators” that connect logic and memory, allowing them to work together efficiently. (Credit: Max Shulaker, Stanford)

 

Stanford engineers have build 3D “high-rise” chips that could leapfrog the performance of the single-story logic and memory chips on today’s circuit cards, which are subject to frequent traffic jams between logic and memory.

The Stanford approach would attempt to end these jams by building layers of logic atop layers of memory to create a tightly interconnected high-rise chip. Many thousands of nanoscale electronic “elevators” would move data between the layers much faster, using less electricity, than the bottleneck-prone wires connecting single-story logic and memory chips today.

The work is led by Subhasish Mitra, a Stanford associate professor of electrical engineering and of computer science, and H.-S. Philip Wong, the Williard R. and Inez Kerr Bell Professor in Stanford’s School of Engineering. They describe their new high-rise chip architecture in a paper being presented at the IEEE International Electron Devices Meeting Dec. 15–17.

The researchers’ innovation leverages three breakthroughs: a new technology for creating transistors using nanotubes, a new type of computer memory that lends itself to multi-story fabrication, and a technique to build these new logic and memory technologies into high-rise structures in a radically different way than previous efforts to stack chips.

“This research is at an early stage, but our design and fabrication techniques are scalable,” Mitra said. “With further development this architecture could lead to computing performance that is much, much greater than anything available today.” Wong said the prototype chip unveiled at IEDM shows how to put logic and memory together into three-dimensional structures that can be mass-produced.

“Paradigm shift is an overused concept, but here it is appropriate,” Wong said. “With this new architecture, electronics manufacturers could put the power of a supercomputer in your hand.”

Overcoming silicon heat

Researchers have been trying to solve a major problem with chip-generated heat by creating carbon nanotubes (CNT)  transistors. Mitra and Wong are presenting a second paper at the conference showing how their team made some of the highest performance CNT transistors ever built.

 

Image of a CNT-based field-effect transistor (FET) using a new high-density process (credit: Mitra/Wong Lab, Stanford)

http://www.kurzweilai.net/images/CNTFET.jpg

Until now the standard process used to grow CNTs did not create sufficient density. The Stanford engineers solved this problem  an ingenious technique. They started by growing CNTs the standard way, on round quartz wafers. Then they created a metal film that acts like a tape. Using this adhesive process, they lifted an entire crop of CNTs off the quartz growth medium and placed it onto a silicon wafer that would become the foundation of their high-rise chip.

They repeated this process 13 times, achieving some of the highest density, highest performance CNTs ever made. Moreover, the Stanford team showed that they could perform this technique on more than one layer of logic as they created their high-rise chip.

 

RRAM memory

Left: Today’s single-story electronic circuit cards, where logic and memory chips exist as separate structures connected by wires, can get jammed with digital traffic between logic and memory. Right: layers of logic and memory create skyscraper chips where data would move up and down on nanoscale “elevators” to avoid traffic jams. (Credit: Mitra/Wong Lab, Stanford)

Wong is a world leader in a new memory technology called “resistive random access memory” (RRAM) which he unveiled at last year’s IEDM conference.

Unlike today’s memory chips, this new storage technology is not based on silicon, but titanium nitride, hafnium oxide and platinum. This formed a metal/oxide/metal sandwich. Applying electricity to this three-metal sandwich one way causes it to resist the flow of electricity. Reversing the polarity causes the structure to conduct electricity again.

The change from resistive to conductive states is how this new memory technology creates digital zeroes and ones.

RRAM uses less energy than current memory, leading to prolonged battery life in mobile devices. Inventing this new memory technology was also the key to creating the high-rise chip because RRAM can be made at much lower temperatures than silicon memory.

Interconnected layers

Max Shulaker and Tony Wu, Stanford graduate students in electrical engineering, created the techniques behind the four-story high-rise chip unveiled at the conference.

The low-heat process for making RRAM and CNTs enabled them to fabricate each layer of memory directly atop each layer of CNT logic. While making each memory layer, they were able to drill thousands of interconnections into the logic layer below. This multiplicity of connections is what enables the high-rise chip to avoid the traffic jams on conventional circuit cards.

There is no way to tightly interconnect layers using today’s conventional silicon-based logic and memory. That’s because it takes so much heat to build a layer of silicon memory — about 1,000 degrees Celsius — that any attempt to do so would melt the logic below.

Previous efforts to stack silicon chips could save space but not avoid the digital traffic jams. That’s because each layer would have to be built separately and connected by wires — which would still be prone to traffic jams, unlike the nanoscale elevators in the Stanford design.

 

 

‘Memristors’ based on transparent electronics offer technology of the future

Memristors are faster, smaller, and use less power than non-volatile flash memory

http://www.kurzweilai.net/memristors-based-on-transparent-electronics-offer-technology-of-the-future

http://www.kurzweilai.net/images/flash-drive.jpg

Transparent electronics (pioneered at Oregon State University) may find one of their newest applications as a next-generation replacement for some uses of non-volatile flash memory, a multi-billion dollar technology nearing its limit of small size and information storage capacity.

Researchers at OSU have confirmed that zinc tin oxide, an inexpensive and environmentally benign compound,  could provide a new, transparent technology where computer memory is based on resistance, instead of an electron charge.

This resistive random access memory, or RRAM, is referred to by some researchers as a “memristor.” Products using this approach could become even smaller, faster and cheaper than the silicon transistors that have revolutionized modern electronics — and transparent as well.

Transparent electronics offer potential for innovative products that don’t yet exist, like information displayed on an automobile windshield, or surfing the web on the glass top of a coffee table.

“Flash memory has taken us a long way with its very small size and low price,” said John Conley, a professor in the OSU School of Electrical Engineering and Computer Science. “But it’s nearing the end of its potential, and memristors are a leading candidate to continue performance improvements.”

Memristors: faster than flash  

Memristors have a simple structure, are able to program and erase information rapidly, and consume little power. They accomplish a function similar to transistor-based flash memory, but with a different approach. Whereas traditional flash memory stores information with an electrical charge, RRAM accomplishes this with electrical resistance. Like flash, it can store information as long as it’s needed.

Flash memory computer chips are ubiquitous in almost all modern electronic products, ranging from cell phones and computers to video games and flat panel televisions.

Thin-film transistors that control liquid crystal displays

Some of the best opportunities for these new amorphous oxide semiconductors are not so much for memory chips, but with thin-film, flat panel displays, researchers say. Private industry has already shown considerable interest in using them for the thin-film transistors that control liquid crystal displays, and one compound approaching commercialization is indium gallium zinc oxide.

But indium and gallium are getting increasingly expensive, and zinc tin oxide — also a transparent compound — appears to offer good performance with lower cost materials. The new research also shows that zinc tin oxide can be used not only for thin-film transistors, but also for memristive memory, Conley said, an important factor in its commercial application.

More work is needed to understand the basic physics and electrical properties of the new compounds, researchers said.

This research was supported by the U.S. Office of Naval Research, the National Science Foundation and the Oregon Nanoscience and Microtechnologies Institute.

references:

Santosh Murali, Jaana S. Rajachidambaram, Seung-Yeol Han, Chih-Hung Chang, Gregory S. Herman, John F. Conley, Resistive switching in zinc-tin-oxide, Solid-State Electronics, 2012, DOI: 10.1016/j.sse.2012.06.016

 

Resistive switching in zinc–tin-oxide

Santosh Murali^a, Jaana S. Rajachidambaram^b, Seung-Yeol Han^b, Chih-Hung Chang^b, Gregory S. Herman^b, John F. Conley Jr.^a,

Solid-State Electronics Jan 2013; 79:248–252    http://dx.doi.org:/10.1016/j.sse.2012.06.016

Bipolar resistive switching is demonstrated in the amorphous oxide semiconductor zinc–tin-oxide (ZTO). A gradual forming process produces improved switching uniformity. Al/ZTO/Pt crossbar devices show switching ratios greater than 10³, long retention times, and good endurance. The resistive switching in these devices is consistent with a combined filamentary/interfacial mechanism. Overall, ZTO shows great potential as a low cost material for embedding memristive memory with thin film transistor logic for large area electronics.

---

Highlights

► We present the first report of resistive switching in zinc–tin-oxide (ZTO). ► ZTO is the leading alternative material to IGZO for TFTs for LCDs. ► ZTO has an advantage over IGZO of lower cost due to the absence of In and Ga. ► Al/ZTO/Pt crossbar RRAM devices show switching ratios greater than 10³. ► ZTO shows promise for embedding RRAM with TFT logic for large area electronics.

Keywords

Memristor; RRAM; Resistive switching; Amorphous oxide semiconductors; Transparent electronics; Zinc–tin-oxide

http://ars.els-cdn.com/content/thumbimage/1-s2.0-S0038110112002304-gr1.sml

 

Method to replace silicon with carbon nanotubes developed by IBM Research

Could work down to the 1.8 nanometer node in the future

http://www.kurzweilai.net/method-to-replace-silicon-with-carbon-nanotubes-developed-by-ibm-research

http://www.kurzweilai.net/images/Mo-CNT-contacts.jpg

Schematic of a set of molybdenum (M0) end-contacted nanotube transistors (credit: Qing Cao et al./Science)

IBM Research has announced a “major engineering breakthrough” that could lead to carbon nanotubes replacing silicon transistors in future computing technologies.

As transistors shrink in size, electrical resistance increases within the contacts, which impedes performance. So IBM researchers invented a metallurgical process similar to microscopic welding that chemically binds the contact’s metal (molybdenum) atoms to the carbon atoms at the ends of nanotubes.

The new method promises to shrink transistor contacts without reducing performance of carbon-nanotube devices, opening a pathway to dramatically faster, smaller, and more powerful computer chips beyond the capabilities of traditional silicon semiconductors.

“This is the kind of breakthrough that we’re committed to making at IBM Research via our $3 billion investment over 5 years in research and development programs aimed a pushing the limits of chip technology,” said Dario Gil, VP, Science & Technology, IBM Research. “Our aim is to help IBM produce high-performance systems capable of handling the extreme demands of new data analytics and cognitive computing applications.”

The development was reported today in the October 2 issue of the journal Science.

 

Overcoming contact resistance

http://www.kurzweilai.net/images/SWNT-transistor-contacts.jpg

Schematic of carbon nanotube transistor contacts. Left: High-resistance side-bonded contact, where the single-wall nanotube (SWNT) (black tube) is partially covered by the metal molybdenum (Mo) (purple dots). Right: low-resistance end-bonded contact, where the SWNT is attached to the molybdenum electrode through carbide bonds, while the carbon atoms (black dots) from the originally covered portion of the SWNT uniformly diffuse out into the Mo electrode (credit: Qing Cao et al./Science)

 

The new “end-bonded contact scheme” allows carbon-nanotube contacts to be shrunken down to below 10 nanometers without deteriorating performance. IBM says the scheme could overcome contact resistance challenges all the way to the 1.8 nanometer node and replace silicon with carbon nanotubes.

Silicon transistors have been made smaller year after year, but they are approaching a point of physical limitation. With Moore’s Law running out of steam, shrinking the size of the transistor — including the channels and contacts — without compromising performance has been a challenge for researchers for decades.

 

http://www.kurzweilai.net/images/SWCNT.jpg

Single wall carbon nanotube (credit: IBM)

 

IBM has previously shown that carbon nanotube transistors can operate as excellent switches at channel dimensions of less than ten nanometers, which is less than half the size of today’s leading silicon technology. Electrons in carbon transistors can move more easily than in silicon-based devices and use less power.

Carbon nanotubes are also flexible and transparent, making them useful for flexible and stretchable electronics or sensors embedded in wearables.

IBM acknowledges that several major manufacturing challenges still stand in the way of commercial devices based on nanotube transistors.

Earlier this summer, IBM unveiled the first 7 nanometer node silicon test chip, pushing the limits of silicon technologies.

references:

• Qing Cao, Shu-Jen Han, Jerry Tersoff, Aaron D. Franklin, Yu Zhu, Zhen Zhang, George S. Tulevski, Jianshi Tang, and Wilfried Haensch. End-bonded contacts for carbon nanotube transistors with low, size-independent resistance. Science 2 October 2015: 350 (6256), 68-72. [DOI:10.1126/science.aac8006]

related:

• IBM Research Breakthrough Paves Way for Post-Silicon Future with Carbon Nanotube Electronics
• Carbon Nanotubes at 9 nm: A Q&A with IBM Research’s Shu-Jen Han

Topics: Computers/Infotech/UI | Electronics | Nanotech/Materials Science

END-BONDED CONTACTS FOR CARBON NANOTUBE TRANSISTORS WITH LOW, SIZE-INDEPENDENT RESISTANCE

Science 2 Oct 2015; 350(6256):68–72      http://dx.doi.org:/10.1126/science.aac8006

Moving beyond the limits of silicon transistors requires both a high-performance channel and high-quality electrical contacts. Carbon nanotubes provide high-performance channels below 10 nanometers, but as with silicon, the increase in contact resistance with decreasing size becomes a major performance roadblock. We report a single-walled carbon nanotube (SWNT) transistor technology with an end-bonded contact scheme that leads to size-independent contact resistance to overcome the scaling limits of conventional side-bonded or planar contact schemes. A high-performance SWNT transistor was fabricated with a sub–10-nanometer contact length, showing a device resistance below 36 kilohms and on-current above 15 microampere per tube. The p-type end-bonded contact, formed through the reaction of molybdenum with the SWNT to form carbide, also exhibited no Schottky barrier. This strategy promises high-performance SWNT transistors, enabling future ultimately scaled device technologies.

 

 

 

 

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Calcium Channel Blocker Potential for Angina

Posted in Acute Myocardial Infarction, Biological Networks, Ca2+ triggered activation, Calcium Signaling, Cardiomyopathy, Cardiovascular Research, Cell Biology, Signaling & Cell Circuits, Chemical Biology and its relations to Metabolic Disease, Clinical & Translational, Curation, Disease Biology, Small Molecules in Development of Therapeutic Drugs, FDA, CE Mark & Global Regulatory Affairs: process management and strategic planning - GCP, GLP, ISO 14155, Frontiers in Cardiology and Cardiovascular Disorders, Gene Regulation, HTN, Myocardial metabolism, Myocardial ischemia, myocardial perfusion, Myocardial adenine nucleotide metabolism, Pharmacotherapy of Cardiovascular Disease, tagged angina, calcium channels, Hypertension, pharmacotherapy on December 11, 2015| Leave a Comment »

Calcium Channel Blocker Potential for Angina

Larry H. Bernstein, MD, FCAP, Curator

LPBI

 

 

Pranidipine    

ANTHONY MELVIN CRASTO, PhD

https://newdrugapprovals.files.wordpress.com/2015/12/str116.jpg

 

Pranidipine , OPC-13340, FRC 8411

Acalas^®

NDA Filing in Japan

A calcium channel blocker potentially for the treatment of angina pectoris and hypertension.

 

CAS No. 99522-79-9

• Molecular FormulaC₂₅H₂₄N₂O₆
• Average mass 448.468

 

see dipine series………..http://organicsynthesisinternational.blogspot.in/p/dipine-series.html

manidipine

 

PAPER

Der Pharmacia Sinica, 2014, 5(1):11-17

https://newdrugapprovals.files.wordpress.com/2015/12/str113.jpg

pelagiaresearchlibrary.com/der-pharmacia-sinica/vol5-iss1/DPS-2014-5-1-11-17.pdf

 

Names
IUPAC name methyl (2E)-phenylprop-2-en-1-yl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate
Other names 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid O5-methyl O3-[(E)-3-phenylprop-2-enyl] ester
Identifiers
CAS Number	99522-79-9
ChEMBL	ChEMBL1096842
ChemSpider	4940726
InChI[show]
Jmol interactive 3D	Image
MeSH	C048161
PubChem	6436048
SMILES[show]
UNII	9DES9QVH58

 

 

 

PATENT	SUBMITTED	GRANTED
Process for the preparation of 1,4 – dihydropyridines and novel 1,4-dihydropyridines useful as therapeutic agents [US2003230478]	2003-12-18
Advanced Formulations and Therapies for Treating Hard-to-Heal Wounds [US2014357645]	2014-08-19	2014-12-04
METHODS OF TREATING CARDIOVASCULAR AND METABOLIC DISEASES [US2014322199]	2012-08-06	2014-10-30
Protein Carrier-Linked Prodrugs [US2014323402]	2012-08-10	2014-10-30
sGC STIMULATORS [US2014323448]	2014-04-29	2014-10-30
TREATMENT OF ARTERIAL WALL BY COMBINATION OF RAAS INHIBITOR AND HMG-CoA REDUCTASE INHIBITOR [US2014323536]	2012-12-07	2014-10-30
Agonists of Guanylate Cyclase Useful For the Treatment of Gastrointestinal Disorders, Inflammation, Cancer and Other Disorders [US2014329738]	2014-03-28	2014-11-06
METHODS, COMPOSITIONS, AND KITS FOR THE TREATMENT OF CANCER [US2014335050]	2012-05-25	2014-11-13
ROR GAMMA MODULATORS [US2014343023]	2012-09-18	2014-11-20
High-Loading Water-Soluable Carrier-Linked Prodrugs [US2014296257]	2012-08-10	2014-10-02

 

 

Synthesis, isolation and use of a common key intermediate for calcium antagonist inhibitors

Neelakandan K.a,b, Manikandan H.b , B. Prabhakarana*, Santosha N.a , Ashok Chaudharia *, Mukund Kulkarnic , Gopalakrishnan Mannathusamyb and Shyam Titirmarea
a API Research Centre, Emcure Pharmaceutical Limited, Hinjawadi, Pune, India bDepartment of Chemistry, Annamalai University, Chidhambaram, India cDepartment of Chemistry, Pune University, Pune, India _________________________________________________________________________________

Pelagia Research Library     www.pelagiaresearchlibrary.com      Der Pharmacia Sinica, 2014, 5(1):11-17

 

The compound (3) synthesized from Nitrobenzaldehyde, tertiary butyl acetoacetate and piperidine can be used as a common intermediate for the production of calcium channel blockers like Nicardipine hydrochloride (1) and Pranidipine hydrochloride (2) with high purity.

 

The last twenty years have witnessed discoveries of calcium antagonists associated with multicoated pharmacodynamics potential which include not only antihypertensive and antiarrhythmic effects of the drugs but also action against excessive calcium entry in the cell of cardiovascular system and subsequent cell damage. Among many classes of calcium channel blockers, 1,4-dihydropyrimidine based drug molecules represented by Felodipine, Clevidipine, Benidipine, Nicardipine and Pranidipine are by far the best to reduce systemic vascular resistance and arterial pressure.

The reported synthetic approaches however proceed with complicated work ups, laborious purification procedures, highly expensive chemicals and low overall yields. (Scheme-I).

Synthetic scheme of Nicardipine and Pranidipine In view of the draw backs associated with previous synthetic approaches there is a strong need for environmentfriendly high yielding process applicable to the multi-kilogram production of calcium antagonist inhibitors. Herein, we report a scalable synthesis for Nicardipine hydrochloride (1) and Pranidipine hydrochloride (2) in fairly high overall yield using key intermediate 3-nitro benzylidene acid (3).Compound (3) was synthesized in two steps using 3-nitrobenzaldehyde, tertiary butyl acetoacetate and piperidine as a base to furnish tertiary butyl ester derivative (10). This was followed by hydrolysis of (10) in TFA and DCM to furnish compound (3) which would serve as a precursor for synthesis of versatile calcium antagonist inhibitors (Scheme-II).

Reported routes for synthesis of Benidipine,1,2 Lercanadipine,3-6 Nimodipine,7-11 Barnidipine12-14 and Manidipine15-16 were explored in our laboratory which involve reaction of nitro benzaldehyde with tertiary butyl acetoacetate using piperidine as a base to get tertiary butyl ester derivative (10). This is further treated with respective reagents to get various calcium channel blockers as shown in scheme 4. Since reported procedures involve in-situ generation of intermediate (3) and its reaction with corresponding fragments, it results in the formation of by-products which ultimately decrease the yield and increase the cost of API.

A novel process of manufacturing benzylidine acid derivative (3) was developed. Use of this intermediate was demonstrated by synthesis of Nicardipine and Pranidipine. This protocol may be employed for synthesis of other calcium channel blockers. In conclusion, a highly efficient, reproducible and scalable process for the synthesis of calcium channel blockers has been developed using (3) as the key intermediate.

 

[1] US 63 365 (Kyowa Hakko; appl.15.4.1982; J-prior.17.4.1981). [2] US 4 448 964 (Kyowa Hakko;15.5.1984; J-prior.17.4.1981). [3] Leonardi, A. et al.: Eur. J. Med.Chem. (EJMCA5) 33,399 (1988). [4] EP 153 016 (Recordati Chem. and Pharm.; appl. 21.1.1985; GB-prior. 14.2.1984). [5] US 4 705 797 (Recordati;10.11.1987; GB-prior. 14.2.1984). [6] WO 9 635 668 (Recordati Chem. and Pharm.; appl. 9.5.1996; I-prior. 12.5.1995). [7] DOS 2 117 571 (Bayer; appl. 10.4.1971). [8] DE 2 117 573 (Bayer; prior.10.4.1971) [9] US 3 799 934 (Bayer;26.3.1974;D-prior.10.4.1971). [10] US 3 932 645 (Bayer;13.1.1976;D-prior.10.4.1971). [11] Meyer, H. et al.: Arzneim.-Forsch. (ARZNAD) 31, 407 (1981); 33, 106 (1983). [12] DE 2 904 552 (Yamanouchi Pharm.; appl. 7.2.1979; J-prior.14.2.1978). [13] US 4 220 649 (Yamanouchi;2.9.1980; J-prior.14.2.1978). [14] CN 85 107 590( Faming Zhuanli Sheqing Gonhali S.; appl. 11.10.1985; J-prior.24.1.1985). [15] EP 94 159 (Takeda; appl. 15.4.1983; J-prior. 10.5.1982). [16] US 4 892 875 (Takeda;9.1.1990; J-prior. 10.5.1982, 11.1.1983).

 

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