Tag Archives: biosensor

The how and why of nanopores

An August 19, 2021 Universidade NOVA de Lisboa ITQB NOVA press release (also on EurekAlert) explains what nanopores are while describing research into determining how their locations can be controlled,

At the simplest of levels, nanopores are (nanometre-sized) holes in an insulating membrane. The hole allows ions to pass through the membrane when a voltage is applied, resulting in a measurable current. When a molecule passes through a nanopore it causes a change in the current, this can be used to characterize and even identify individual molecules. Nanopores are extremely powerful single-molecule biosensing devices and can be used to detect and sequence DNA, RNA, and even proteins. Recently, it has been used in the SARS-CoV-2 virus sequencing.  

Solid-state nanopores are an extremely versatile type of nanopore formed in ultrathin membranes (less than 50 nanometres), made from materials such as silicon nitride (SiNx). Solid-state nanopores can be created with a range of diameters and can withstand a multitude of conditions (discover more about solid-state nanopore fabrication techniques here). One of the most appealing techniques with which to fabricate nanopores is Controlled Breakdown (CBD). This technique is quick, reduces fabrication costs, does not require specialized equipment, and can be automated.

CBD is a technique in which an electric field is applied across the membrane to induce a current. At some point, a spike in the current is observed, signifying pore formation. The voltage is then quickly reduced to ensure the fabrication of a single, small nanopore.

The mechanisms underlying this process have not been fully elucidated thus an international team involving ITQB NOVA decided to further investigate how electrical conduction through the membrane occurs during breakdown, namely how oxidation and reduction reactions (also called redox reactions, they imply electron loss or gain, respectively) influence the process. To do this, the team created three devices in which the electric field is applied to the membrane (a silicon-rich SiNx membrane) in different ways: via metal electrodes on both sides of the membrane; via electrolyte solutions on both sides of the membrane; and via a mixed device with a metal electrode on one side and an electrolyte solution on the other.

Results showed that redox reactions must occur at the membrane-electrolyte interface, whilst the metal electrodes circumvent this need. The team also demonstrated that, because of this phenomenon, nanopore fabrication could be localized to certain regions by performing CBD with metal microelectrodes on the membrane surface. Finally, by varying the content of silicon in the membrane, the investigators demonstrated that conduction and nanopore formation is highly dependent on the membrane material since it limits the electrical current in the membrane.

“Controlling the location of nanopores has been of interest to us for a number of years”, says James Yates. Pedro Sousa adds that “our findings suggest that CBD can be used to integrate pores with complementary micro or nanostructures, such as tunneling electrodes or field-effect sensors, across a range of different membrane materials.”  These devices may then be used for the detection of specific molecules, such as proteins, DNA, or antibodies, and applied to a wide array of scenarios, including pandemic surveillance or food safety.

This project was developed by a research team led by ITQB NOVA’s James Yates and has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement No 724300 and 875525). Co-author Pedro Miguel Sousa is also from ITQB NOVA. The other consortium members are from the University of Oxford, Oak Ridge National Laboratory, Imperial College London and Queen Mary University of London. The authors would like to thank Andrew Briggs for providing financial support.

Here’s a link to and a citation for the paper,

Understanding Electrical Conduction and Nanopore Formation During Controlled Breakdown by Jasper P. Fried, Jacob L. Swett, Binoy Paulose Nadappuram, Aleksandra Fedosyuk, Pedro Miguel Sousa, Dayrl P. Briggs, Aleksandar P. Ivanov, Joshua B. Edel, Jan A. Mol, James R. Yates. Small DOI: https://doi.org/10.1002/smll.202102543 First published: 01 August 2021

This paper is open access.

Living plants detect arsenic by way of embedded nanosensors

There’s a lot of arsenic in the world and it’s often a factor in making water undrinkable. When that water is used in farming It also pollutes soil and enters food-producing plants. A December 11, 2020 news item on Nanowerk announces research into arsenic detectors in plants,

Researchers have developed a living plant-based sensor that can in real-time detect and monitor levels of arsenic, a highly toxic heavy metal, in the soil. Arsenic pollution is a major threat to humans and ecosystems in many Asia Pacific countries.

Caption: Non-destructive plant nanobionic sensor embedded within leaves to report arsenic levels within plants to portable electronics, enabling real-time monitoring of arsenic uptake in living plants. Credit: Dr. Tedrick Thomas Salim Lew

I was not able to find the source for the news item but I did locate something close. From a December 13, 2020 Singapore-Massachusetts Institute of Technology (MIT) Alliance for Research and Technology (SMART), also on EurekAlert,

Scientists from the Disruptive and Sustainable Technologies for Agricultural Precision (DiSTAP) research group at the Singapore-MIT Alliance for Research and Technology (SMART), MIT’s research enterprise in Singapore, have engineered a novel type of plant nanobionic optical sensor that can detect and monitor, in real time, levels of the highly toxic heavy metal arsenic in the underground environment. This development provides significant advantages over conventional methods used to measure arsenic in the environment and will be important for both environmental monitoring and agricultural applications to safeguard food safety, as arsenic is a contaminant in many common agricultural products such as rice, vegetables, and tea leaves.

Arsenic and its compounds are a serious threat to humans and ecosystems. Long-term exposure to arsenic in humans can cause a wide range of detrimental health effects, including cardiovascular disease such as heart attack, diabetes, birth defects, severe skin lesions, and numerous cancers including those of the skin, bladder, and lung. Elevated levels of soil arsenic as a result of anthropogenic activities such as mining and smelting are also harmful to plants, inhibiting growth and resulting in substantial crop losses.

Food crops can absorb arsenic from the soil, leading to contamination of food and produce consumed by humans. Arsenic in underground environments can also contaminate groundwater and other underground water sources, the long-term consumption of which can cause severe health issues. As such, developing accurate, effective, and easy-to-deploy arsenic sensors is important to protect both the agriculture industry and wider environmental safety.

The novel optical nanosensors exhibit changes in their fluorescence intensity upon detecting arsenic. Embedded in plant tissues, with no detrimental effects on the plant, these sensors provide a nondestructive way to monitor the internal dynamics of arsenic taken up by plants from the soil. This integration of optical nanosensors within living plants enables the conversion of plants into self-powered detectors of arsenic from their natural environment, marking a significant upgrade from the time- and equipment-intensive arsenic sampling methods of current conventional methods.

“Our plant-based nanosensor is notable not only for being the first of its kind, but also for the significant advantages it confers over conventional methods of measuring arsenic levels in the below-ground environment, requiring less time, equipment, and manpower,” says Lew. “We envision that this innovation will eventually see wide use in the agriculture industry and beyond. I am grateful to SMART DiSTAP and the Temasek Life Sciences Laboratory (TLL), both of which were instrumental in idea generation and scientific discussion as well as research funding for this work.”

Besides detecting arsenic in rice and spinach, the team also used a species of fern, Pteris cretica, which can hyperaccumulate arsenic. This fern species can absorb and tolerate high levels of arsenic with no detrimental effect — engineering an ultrasensitive plant-based arsenic detector, capable of detecting very low concentrations of arsenic, as low as 0.2 parts per billion. In contrast, the regulatory limit for arsenic detectors is 10 parts per billion. Notably, the novel nanosensors can also be integrated into other species of plants. The researchers say this is the first successful demonstration of living plant-based sensors for arsenic and represents a groundbreaking advancement that could prove highly useful in both agricultural research (e.g., to monitor arsenic taken up by edible crops for food safety) and general environmental monitoring.

Previously, conventional methods of measuring arsenic levels included regular field sampling, plant tissue digestion, extraction, and analysis using mass spectrometry. These methods are time-consuming, require extensive sample treatment, and often involve the use of bulky and expensive instrumentation. The new approach couples nanoparticle sensors with plants’ natural ability to efficiently extract analytes via the roots and transport them. This allows for the detection of arsenic uptake in living plants in real time, with portable, inexpensive electronics such as a portable Raspberry Pi platform equipped with a charge-coupled device camera akin to a smartphone camera.

Co-author, DiSTAP co-lead principal investigator, and MIT Professor Michael Strano adds, “This is a hugely exciting development, as, for the first time, we have developed a nanobionic sensor that can detect arsenic — a serious environmental contaminant and potential public health threat. With its myriad advantages over older methods of arsenic detection, this novel sensor could be a game-changer, as it is not only more time-efficient, but also more accurate and easier to deploy than older methods. It will also help plant scientists in organizations such as TLL to further produce crops that resist uptake of toxic elements. Inspired by TLL’s recent efforts to create rice crops which take up less arsenic, this work is a parallel effort to further support SMART DiSTAP’s efforts in food security research, constantly innovating and developing new technological capabilities to improve Singapore’s food quality and safety.”

The research is carried out by SMART and supported by the National Research Foundation (NRF) Singapore under its Campus for Research Excellence And Technological Enterprise (CREATE) program.

Led by MIT’s Strano and Singapore co-lead principal investigator Professor Chua Nam Hai, DiSTAP is one of the five Interdisciplinary Research Groups (IRGs) in SMART. The DiSTAP program addresses deep problems in food production in Singapore and the world by developing a suite of impactful and novel analytical genetic and biosynthetic technologies. The goal is to fundamentally change how plant biosynthetic pathways are discovered, monitored, engineered, and ultimately translated to meet the global demand for food and nutrients. Scientists from MIT, TTL, Nanyang Technological University, and National University of Singapore are collaboratively developing new tools for the continuous measurement of important plant metabolites and hormones for novel discovery, deeper understanding and control of plant biosynthetic pathways in ways not yet possible, especially in the context of green leafy vegetables; leveraging these new techniques to engineer plants with highly desirable properties for global food security, including high yield density production, drought and pathogen resistance and biosynthesis of high-value commercial products; developing tools for producing hydrophobic food components in industry-relevant microbes; developing novel microbial and enzymatic technologies to produce volatile organic compounds that can protect and/or promote growth of leafy vegetables; and applying these technologies to improve urban farming.

Here’s a link to and a citation for the paper,

Plant Nanobionic Sensors for Arsenic Detection by Tedrick Thomas Salim Lew, Minkyung Park, Jianqiao Cui, Michael S. Strano. Advanced Materials DOI: https://doi.org/10.1002/adma.202005683 First published: 26 November 2020

This paper is behind a paywall.

Nanomushroom sensors

Schematic illustration of cells (blue mountain-like shapes) on top of nanoscale mushroom-like structures with silicone dioxide stems and gold caps, which have the potential to detect cell proliferation in real-time. Courtesy: OIST

The nanomushroom sensors depicted in the above illustration and announced in a February 23, 2018 news item on Nanowerk probably aren’t edible but they certainly make up for that deficiency with other properties,

A small rectangle of pink glass, about the size of a postage stamp, sits on Professor Amy Shen’s desk. Despite its outwardly modest appearance, this little glass slide has the potential to revolutionize a wide range of processes, from monitoring food quality to diagnosing diseases.

The slide is made of a ‘nanoplasmonic’ material — its surface is coated in millions of gold nanostructures, each just a few billionths of a square meter in size. Plasmonic materials absorb and scatter light in interesting ways, giving them unique sensing properties. Nanoplasmonic materials have attracted the attention of biologists, chemists, physicists and material scientists, with possible uses in a diverse array of fields, such as biosensing, data storage, light generation and solar cells.

A February 23, 2018 Okinawa Institute of Science and Technology Graduate University (OIST) press release (also on EurekAlert), which originated the news item, provides more detail,

In several recent papers, Prof. Shen and colleagues at the Micro/Bio/Nanofluidics Unit at the Okinawa Institute of Science and Technology (OIST), described their creation of a new biosensing material that can be used to monitor processes in living cells.

“One of the major goals of nanoplasmonics is to search for better ways to monitor processes in living cells in real time,” says Prof. Shen. Capturing such information can reveal clues about cell behavior, but creating nanomaterials on which cells can survive for long periods of time yet don’t interfere with the cellular processes being measured is a challenge, she explains.

Counting Dividing Cells

One of the team’s new biosensors is made from a nanoplasmonic material that is able to accommodate a large number of cells on a single substrate and to monitor cell proliferation, a fundamental process involving cell growth and division, in real time. Seeing this process in action can reveal important insights into the health and functions of cells and tissues.

Researchers in OIST’s Micro/Bio/Nanofluidics Unit described the sensor in a study recently published in the journal Advanced Biosystems [citation and link follow this press release].

The most attractive feature of the material is that it allows cells to survive over long time periods. “Usually, when you put live cells on a nanomaterial, that material is toxic and it kills the cells,” says Dr. Nikhil Bhalla, a postdoctoral researcher at OIST and first author of the paper. “However, using our material, cells survived for over seven days.” The nanoplasmonic material is also highly sensitive: It can detect an increase in cells as small as 16 in 1000 cells.

The material looks just like an ordinary pieces of glass. However, the surface is coated in tiny nanoplasmonic mushroom-like structures, known as nanomushrooms, with stems of silicon dioxide and caps of gold. Together, these form a biosensor capable of detecting interactions at the molecular level.

The biosensor works by using the nanomushroom caps as optical antennae. When white light passes through the nanoplasmonic slide, the nanomushrooms absorb and scatter some of the light, changing its properties. The absorbance and scattering of light is determined by the size, shape and material of the nanomaterial and, more importantly, it is also affected by any medium in close proximity to the nanomushroom, such as cells that have been placed on the slide. By measuring how the light has changed once it emerges through the other side of the slide, the researchers can detect and monitor processes occurring on the sensor surface, such as cell division.

“Normally, you have to add labels, such as dyes or molecules, to cells, to be able to count dividing cells,” says Dr. Bhalla. “However, with our method, the nanomushrooms can sense them directly.”

Scaling Up

This work builds on a new method, developed by scientists at the Micro/Bio/Nanofluidics Unit at OIST, for fabricating nanomushroom biosensors. The technique was published in the journal ACS Applied Materials and Interfaces in December 2017.

Producing large-scale nanoplasmonic materials is challenging because it is difficult to ensure uniformity across the entire material surface. For this reason, biosensors for routine clinical examinations, such as disease testing, are still lacking.

In response to this problem, the OIST researchers developed a novel printing technique to create large-scale nanomushroom biosensors. With their method, they were able to develop a material consisting of approximately one million mushroom-like structures on a 2.5cm by 7.5cm silicon dioxide substrate.

“Our technique is like taking a stamp, covering it with ink made from biological molecules, and printing onto the nanoplasmonic slide,” says Shivani Sathish, a PhD student at OIST and co-author of the paper. The biological molecules increase the sensitivity of the material, meaning it can sense extremely low concentrations of substances, such as antibodies, and thus potentially detect diseases in their earliest stages.

“Using our method, it is possible to create a highly sensitive biosensor that can detect even single molecules,” says Dr. Bhalla, first author of the paper.

Plasmonic and nanoplasmonic sensors offer important tools for many fields, from electronics to food production to medicine. For example, in December 2017, second year Ph.D student Ainash Garifullina from the Unit developed a new plasmonic material for monitoring the quality of food products during the manufacturing process. The results were published in the journal Analytical Methods.

Prof. Shen and her unit say that, in the future, nanoplasmonic materials may even be integrated with emerging technologies, such as wireless systems in microfluidic devices, allowing users to take readings remotely and thereby minimizing the risk of contamination.

Here’s a link to and a citation for the paper,

Large-Scale Nanophotonic Structures for Long-Term Monitoring of Cell Proliferation by Nikhil Bhalla, Shivani Sathish, Abhishek Sinha, and Amy Q. Shen. Advanced Biosystems Vol. 2 Issue 2 DOI: 10.1002/adbi.201700258 Version of Record online: 19 JAN 2018

© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

This paper is behind a paywall.

Here’s a link to and a citation for the earlier paper,

Probing specific gravity in real-time with graphene oxide plasmonics by Ainash Garifullina, Nikhil Bhalla, and Amy Q. Shen. Anal. Methods 2018, 10, 290-297 DOI: 10.1039/C7AY02423A first published [online] on 06 Dec 2017

This paper is open access provided you have registered for a free account.

US Dept. of Agriculture announces its nanotechnology research grants

I don’t always stumble across the US Department of Agriculture’s nanotechnology research grant announcements but I’m always grateful when I do as it’s good to find out about  nanotechnology research taking place in the agricultural sector. From a July 21, 2017 news item on Nanowerk,,

The U.S. Department of Agriculture’s (USDA) National Institute of Food and Agriculture (NIFA) today announced 13 grants totaling $4.6 million for research on the next generation of agricultural technologies and systems to meet the growing demand for food, fuel, and fiber. The grants are funded through NIFA’s Agriculture and Food Research Initiative (AFRI), authorized by the 2014 Farm Bill.

“Nanotechnology is being rapidly implemented in medicine, electronics, energy, and biotechnology, and it has huge potential to enhance the agricultural sector,” said NIFA Director Sonny Ramaswamy. “NIFA research investments can help spur nanotechnology-based improvements to ensure global nutritional security and prosperity in rural communities.”

A July 20, 2017 USDA news release, which originated the news item, lists this year’s grants and provides a brief description of a few of the newly and previously funded projects,

Fiscal year 2016 grants being announced include:

Nanotechnology for Agricultural and Food Systems

  • Kansas State University, Manhattan, Kansas, $450,200
  • Wichita State University, Wichita, Kansas, $340,000
  • University of Massachusetts, Amherst, Massachusetts, $444,550
  • University of Nevada, Las Vegas, Nevada,$150,000
  • North Dakota State University, Fargo, North Dakota, $149,000
  • Cornell University, Ithaca, New York, $455,000
  • Cornell University, Ithaca, New York, $450,200
  • Oregon State University, Corvallis, Oregon, $402,550
  • University of Pennsylvania, Philadelphia, Pennsylvania, $405,055
  • Gordon Research Conferences, West Kingston, Rhode Island, $45,000
  • The University of Tennessee,  Knoxville, Tennessee, $450,200
  • Utah State University, Logan, Utah, $450,200
  • The George Washington University, Washington, D.C., $450,200

Project details can be found at the NIFA website (link is external).

Among the grants, a University of Pennsylvania project will engineer cellulose nanomaterials [emphasis mine] with high toughness for potential use in building materials, automotive components, and consumer products. A University of Nevada-Las Vegas project will develop a rapid, sensitive test to detect Salmonella typhimurium to enhance food supply safety.

Previously funded grants include an Iowa State University project in which a low-cost and disposable biosensor made out of nanoparticle graphene that can detect pesticides in soil was developed. The biosensor also has the potential for use in the biomedical, environmental, and food safety fields. University of Minnesota (link is external) researchers created a sponge that uses nanotechnology to quickly absorb mercury, as well as bacterial and fungal microbes from polluted water. The sponge can be used on tap water, industrial wastewater, and in lakes. It converts contaminants into nontoxic waste that can be disposed in a landfill.

NIFA invests in and advances agricultural research, education, and extension and promotes transformative discoveries that solve societal challenges. NIFA support for the best and brightest scientists and extension personnel has resulted in user-inspired, groundbreaking discoveries that combat childhood obesity, improve and sustain rural economic growth, address water availability issues, increase food production, find new sources of energy, mitigate climate variability and ensure food safety. To learn more about NIFA’s impact on agricultural science, visit www.nifa.usda.gov/impacts, sign up for email updates (link is external) or follow us on Twitter @USDA_NIFA (link is external), #NIFAImpacts (link is external).

Given my interest in nanocellulose materials (Canada was/is a leader in the production of cellulose nanocrystals [CNC] but there has been little news about Canadian research into CNC applications), I used the NIFA link to access the table listing the grants and clicked on ‘brief’ in the View column in the University of Pennsylania row to find this description of the project,

ENGINEERING CELLULOSE NANOMATERIALS WITH HIGH TOUGHNESS

NON-TECHNICAL SUMMARY: Cellulose nanofibrils (CNFs) are natural materials with exceptional mechanical properties that can be obtained from renewable plant-based resources. CNFs are stiff, strong, and lightweight, thus they are ideal for use in structural materials. In particular, there is a significant opportunity to use CNFs to realize polymer composites with improved toughness and resistance to fracture. The overall goal of this project is to establish an understanding of fracture toughness enhancement in polymer composites reinforced with CNFs. A key outcome of this work will be process – structure – fracture property relationships for CNF-reinforced composites. The knowledge developed in this project will enable a new class of tough CNF-reinforced composite materials with applications in areas such as building materials, automotive components, and consumer products.The composite materials that will be investigated are at the convergence of nanotechnology and bio-sourced material trends. Emerging nanocellulose technologies have the potential to move biomass materials into high value-added applications and entirely new markets.

It’s not the only nanocellulose material project being funded in this round, there’s this at North Dakota State University, from the NIFA ‘brief’ project description page,

NOVEL NANOCELLULOSE BASED FIRE RETARDANT FOR POLYMER COMPOSITES

NON-TECHNICAL SUMMARY: Synthetic polymers are quite vulnerable to fire.There are 2.4 million reported fires, resulting in 7.8 billion dollars of direct property loss, an estimated 30 billion dollars of indirect loss, 29,000 civilian injuries, 101,000 firefighter injuries and 6000 civilian fatalities annually in the U.S. There is an urgent need for a safe, potent, and reliable fire retardant (FR) system that can be used in commodity polymers to reduce their flammability and protect lives and properties. The goal of this project is to develop a novel, safe and biobased FR system using agricultural and woody biomass. The project is divided into three major tasks. The first is to manufacture zinc oxide (ZnO) coated cellulose nanoparticles and evaluate their morphological, chemical, structural and thermal characteristics. The second task will be to design and manufacture polymer composites containing nano sized zinc oxide and cellulose crystals. Finally the third task will be to test the fire retardancy and mechanical properties of the composites. Wbelieve that presence of zinc oxide and cellulose nanocrystals in polymers will limit the oxygen supply by charring, shielding the surface and cellulose nanocrystals will make composites strong. The outcome of this project will help in developing a safe, reliable and biobased fire retardant for consumer goods, automotive, building products and will help in saving human lives and property damage due to fire.

One day, I hope to hear about Canadian research into applications for nanocellulose materials. (fingers crossed for good luck)

Semi-living gloves as sensors

Researchers at the Massachusetts Institute of Technology (MIT) are calling it a new ‘living material’ according to a Feb. 16, 2017 news item on Nanowerk,

Engineers and biologists at MIT have teamed up to design a new “living material” — a tough, stretchy, biocompatible sheet of hydrogel injected with live cells that are genetically programmed to light up in the presence of certain chemicals.

Researchers have found that the hydrogel’s mostly watery environment helps keep nutrients and programmed bacteria alive and active. When the bacteria reacts to a certain chemical, the bacteria are programmed to light up, as seen on the left. Courtesy of the researchers

A Feb. 15, 2017 MIT news release, which originated the news item, provides more information about this work,

In a paper published this week in the Proceedings of the National Academy of Sciences, the researchers demonstrate the new material’s potential for sensing chemicals, both in the environment and in the human body.

The team fabricated various wearable sensors from the cell-infused hydrogel, including a rubber glove with fingertips that glow after touching a chemically contaminated surface, and bandages that light up when pressed against chemicals on a person’s skin.

Xuanhe Zhao, the Robert N. Noyce Career Development associate professor of mechanical engineering at MIT, says the group’s living material design may be adapted to sense other chemicals and contaminants, for uses ranging from crime scene investigation and forensic science, to pollution monitoring and medical diagnostics.

“With this design, people can put different types of bacteria in these devices to indicate toxins in the environment, or disease on the skin,” says Timothy Lu, associate professor of biological engineering and of electrical engineering and computer science. “We’re demonstrating the potential for living materials and devices.”

The paper’s co-authors are graduate students Xinyue Liu, Tzu-Chieh Tang, Eleonore Tham, Hyunwoo Yuk, and Shaoting Lin.

Infusing life in materials

Lu and his colleagues in MIT’s Synthetic Biology Group specialize in creating biological circuits, genetically reprogramming the biological parts in living cells such as E. coli to work together in sequence, much like logic steps in an electrical circuit. In this way, scientists can reengineer living cells to carry out specific functions, including the ability to sense and signal the presence of viruses and toxins.

However, many of these newly programmed cells have only been demonstrated in situ, within Petri dishes, where scientists can carefully control the nutrient levels necessary to keep the cells alive and active — an environment that has proven extremely difficult to replicate in synthetic materials.

“The challenge to making living materials is how to maintain those living cells, to make them viable and functional in the device,” Lu says. “They require humidity, nutrients, and some require oxygen. The second challenge is how to prevent them from escaping from the material.”

To get around these roadblocks, others have used freeze-dried chemical extracts from genetically engineered cells, incorporating them into paper to create low-cost, virus-detecting diagnostic strips. But extracts, Lu says, are not the same as living cells, which can maintain their functionality over a longer period of time and may have higher sensitivity for detecting pathogens.

Other groups have seeded heart muscle cells onto thin rubber films to make soft, “living” actuators, or robots. When bent repeatedly, however, these films can crack, allowing the live cells to leak out.

A lively host

Zhao’s group in MIT’s Soft Active Materials Laboratory has developed a material that may be ideal for hosting living cells. For the past few years, his team has come up with various formulations of hydrogel — a tough, highly stretchable, biocompatible material made from a mix of polymer and water. Their latest designs have contained up to 95 percent water, providing an environment which Zhao and Lu recognized might be suitable for sustaining living cells. The material also resists cracking even when repeatedly stretched and pulled — a property that could help contain cells within the material.

The two groups teamed up to integrate Lu’s genetically programmed bacterial cells into Zhao’s sheets of hydrogel material. They first fabricated layers of hydrogel and patterned narrow channels within the layers using 3-D printing and micromolding techniques. They fused the hydrogel to a layer of elastomer, or rubber, that is porous enough to let in oxygen. They then injected E. coli cells into the hydrogel’s channels. The cells were programmed to fluoresce, or light up, when in contact with certain chemicals that pass through the hydrogel, in this case a natural compound known as DAPG (2,4-diacetylphloroglucinol).

The researchers then soaked the hydrogel/elastomer material in a bath of nutrients which infused throughout the hydrogel and helped to keep the bacterial cells alive and active for several days.

To demonstrate the material’s potential uses, the researchers first fabricated a sheet of the material with four separate, narrow channels, each containing a type of bacteria engineered to glow green in response to a different chemical compound. They found each channel reliably lit up when exposed to its respective chemical.

Next, the team fashioned the material into a bandage, or “living patch,” patterned with channels containing bacteria sensitive to rhamnose, a naturally occurring sugar. The researchers swabbed a volunteer’s wrist with a cotton ball soaked in rhamnose, then applied the hydrogel patch, which instantly lit up in response to the chemical.

Finally, the researchers fabricated a hydrogel/elastomer glove whose fingertips contained swirl-like channels, each of which they filled with different chemical-sensing bacterial cells. Each fingertip glowed in response to picking up a cotton ball soaked with a respective compound.

The group has also developed a theoretical model to help guide others in designing similar living materials and devices.

“The model helps us to design living devices more efficiently,” Zhao says. “It tells you things like the thickness of the hydrogel layer you should use, the distance between channels, how to pattern the channels, and how much bacteria to use.”

Ultimately, Zhao envisions products made from living materials, such as gloves and rubber soles lined with chemical-sensing hydrogel, or bandages, patches, and even clothing that may detect signs of infection or disease.

Here’s a link to and a citation for the paper,

Stretchable living materials and devices with hydrogel–elastomer hybrids hosting programmed cells by Xinyue Liu, Tzu-Chieh Tang, Eléonore Tham, Hyunwoo Yuk, Shaoting Lin, Timothy K. Lu, and Xuanhe Zhao. PNAS February 15, 2017 doi: 10.1073/pnas.1618307114 Published online before print February 15, 2017

This paper appears to be open access.

Spinach and plant nanobionics

Who knew that spinach leaves could be turned into electronic devices? The answer is: engineers at the Massachusetts Institute of Technology, according to an Oct. 31, 2016 news item on phys.org,

Spinach is no longer just a superfood: By embedding leaves with carbon nanotubes, MIT engineers have transformed spinach plants into sensors that can detect explosives and wirelessly relay that information to a handheld device similar to a smartphone.

This is one of the first demonstrations of engineering electronic systems into plants, an approach that the researchers call “plant nanobionics.”

An Oct. 31, 2016 MIT news release (also on EurekAlert), which originated the news item, describes the research further (Note: Links have been removed),

“The goal of plant nanobionics is to introduce nanoparticles into the plant to give it non-native functions,” says Michael Strano, the Carbon P. Dubbs Professor of Chemical Engineering at MIT and the leader of the research team.

In this case, the plants were designed to detect chemical compounds known as nitroaromatics, which are often used in landmines and other explosives. When one of these chemicals is present in the groundwater sampled naturally by the plant, carbon nanotubes embedded in the plant leaves emit a fluorescent signal that can be read with an infrared camera. The camera can be attached to a small computer similar to a smartphone, which then sends an email to the user.

“This is a novel demonstration of how we have overcome the plant/human communication barrier,” says Strano, who believes plant power could also be harnessed to warn of pollutants and environmental conditions such as drought.

Strano is the senior author of a paper describing the nanobionic plants in the Oct. 31 [2016] issue of Nature Materials. The paper’s lead authors are Min Hao Wong, an MIT graduate student who has started a company called Plantea to further develop this technology, and Juan Pablo Giraldo, a former MIT postdoc who is now an assistant professor at the University of California at Riverside.

Environmental monitoring

Two years ago, in the first demonstration of plant nanobionics, Strano and former MIT postdoc Juan Pablo Giraldo used nanoparticles to enhance plants’ photosynthesis ability and to turn them into sensors for nitric oxide, a pollutant produced by combustion.

Plants are ideally suited for monitoring the environment because they already take in a lot of information from their surroundings, Strano says.

“Plants are very good analytical chemists,” he says. “They have an extensive root network in the soil, are constantly sampling groundwater, and have a way to self-power the transport of that water up into the leaves.”

Strano’s lab has previously developed carbon nanotubes that can be used as sensors to detect a wide range of molecules, including hydrogen peroxide, the explosive TNT, and the nerve gas sarin. When the target molecule binds to a polymer wrapped around the nanotube, it alters the tube’s fluorescence.

In the new study, the researchers embedded sensors for nitroaromatic compounds into the leaves of spinach plants. Using a technique called vascular infusion, which involves applying a solution of nanoparticles to the underside of the leaf, they placed the sensors into a leaf layer known as the mesophyll, which is where most photosynthesis takes place.

They also embedded carbon nanotubes that emit a constant fluorescent signal that serves as a reference. This allows the researchers to compare the two fluorescent signals, making it easier to determine if the explosive sensor has detected anything. If there are any explosive molecules in the groundwater, it takes about 10 minutes for the plant to draw them up into the leaves, where they encounter the detector.

To read the signal, the researchers shine a laser onto the leaf, prompting the nanotubes in the leaf to emit near-infrared fluorescent light. This can be detected with a small infrared camera connected to a Raspberry Pi, a $35 credit-card-sized computer similar to the computer inside a smartphone. The signal could also be detected with a smartphone by removing the infrared filter that most camera phones have, the researchers say.

“This setup could be replaced by a cell phone and the right kind of camera,” Strano says. “It’s just the infrared filter that would stop you from using your cell phone.”

Using this setup, the researchers can pick up a signal from about 1 meter away from the plant, and they are now working on increasing that distance.

Michael McAlpine, an associate professor of mechanical engineering at the University of Minnesota, says this approach holds great potential for engineering not only sensors but many other kinds of bionic plants that might receive radio signals or change color.

“When you have manmade materials infiltrated into a living organism, you can have plants do things that plants don’t ordinarily do,” says McAlpine, who was not involved in the research. “Once you start to think of living organisms like plants as biomaterials that can be combined with electronic materials, this is all possible.”

“A wealth of information”

In the 2014 plant nanobionics study, Strano’s lab worked with a common laboratory plant known as Arabidopsis thaliana. However, the researchers wanted to use common spinach plants for the latest study, to demonstrate the versatility of this technique. “You can apply these techniques with any living plant,” Strano says.

So far, the researchers have also engineered spinach plants that can detect dopamine, which influences plant root growth, and they are now working on additional sensors, including some that track the chemicals plants use to convey information within their own tissues.

“Plants are very environmentally responsive,” Strano says. “They know that there is going to be a drought long before we do. They can detect small changes in the properties of soil and water potential. If we tap into those chemical signaling pathways, there is a wealth of information to access.”

These sensors could also help botanists learn more about the inner workings of plants, monitor plant health, and maximize the yield of rare compounds synthesized by plants such as the Madagascar periwinkle, which produces drugs used to treat cancer.

“These sensors give real-time information from the plant. It is almost like having the plant talk to us about the environment they are in,” Wong says. “In the case of precision agriculture, having such information can directly affect yield and margins.”

Once getting over the excitement, questions spring to mind. How could this be implemented? Is somebody  going to plant a field of spinach and then embed the leaves so they can detect landmines? How will anyone know where to plant the spinach? And on a different track, is this spinach edible? I suspect that if spinach can be successfully used as a sensor, it might not be for explosives but for pollution as the researchers suggest.

Here’s a link to and a citation for the paper,

Nitroaromatic detection and infrared communication from wild-type plants using plant nanobionics by Min Hao Wong, Juan P. Giraldo, Seon-Yeong Kwak, Volodymyr B. Koman, Rosalie Sinclair, Tedrick Thomas Salim Lew, Gili Bisker, Pingwei Liu, & Michael S. Strano. Nature Materials (2016) doi:10.1038/nmat4771 Published online 31 October 2016

This paper is behind a paywall.

The last posting here which featured Strano’s research is in an Aug. 25, 2015 piece about carbon nanotubes and medical sensors.

Device detects molecules associated with neurodegenerative diseases

It’s nice to get notice of research in South America, an area for which I rarely stumble across any news releases. Brazilian researchers have developed a device that could help diagnose neurodegenerative diseases such as Alzheimer’s and and Parkinson’s as well as some cancers according to a May 20, 2016 news item on Nanotechnology Now,

A biosensor developed by researchers at the National Nanotechnology Laboratory (LNNano) in Campinas, São Paulo State, Brazil, has been proven capable of detecting molecules associated with neurodegenerative diseases and some types of cancer.

The device is basically a single-layer organic nanometer-scale transistor on a glass slide. It contains the reduced form of the peptide glutathione (GSH), which reacts in a specific way when it comes into contact with the enzyme glutathione S-transferase (GST), linked to Parkinson’s, Alzheimer’s and breast cancer, among other diseases. The GSH-GST reaction is detected by the transistor, which can be used for diagnostic purposes.

The project focuses on the development of point-of-care devices by researchers in a range of knowledge areas, using functional materials to produce simple sensors and microfluidic systems for rapid diagnosis.

A May 19, 2016 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) press release, which originated the news item, provides more detail,

“Platforms like this one can be deployed to diagnose complex diseases quickly, safely and relatively cheaply, using nanometer-scale systems to identify molecules of interest in the material analyzed,” explained Carlos Cesar Bof Bufon, Head of LNNano’s Functional Devices & Systems Lab (DSF) and a member of the research team for the project, whose principal investigator is Lauro Kubota, a professor at the University of Campinas’s Chemistry Institute (IQ-UNICAMP).

In addition to portability and low cost, the advantages of the nanometric biosensor include its sensitivity in detecting molecules, according to Bufon.

“This is the first time organic transistor technology has been used in detecting the pair GSH-GST, which is important in diagnosing degenerative diseases, for example,” he explained. “The device can detect such molecules even when they’re present at very low levels in the examined material, thanks to its nanometric sensitivity.” A nanometer (nm) is one billionth of a meter (10-9 meter), or one millionth of a millimeter.

The system can be adapted to detect other substances, such as molecules linked to different diseases and elements present in contaminated material, among other applications. This requires replacing the molecules in the sensor with others that react with the chemicals targeted by the test, which are known as analytes.

The team is working on paper-based biosensors to lower the cost even further and to improve portability and facilitate fabrication as well as disposal.

The challenge is that paper is an insulator in its usual form. Bufon has developed a technique to make paper conductive and capable of transporting sensing data by impregnating cellulose fibers with polymers that have conductive properties.

The technique is based on in situ synthesis of conductive polymers. For the polymers not to remain trapped on the surface of the paper, they have to be synthesized inside and between the pores of the cellulose fibers. This is done by gas-phase chemical polymerization: a liquid oxidant is infiltrated into the paper, which is then exposed to monomers in the gas phase. A monomer is a molecule of low molecular weight capable of reacting with identical or different molecules of low molecular weight to form a polymer.

The monomers evaporate under the paper and penetrate the pores of the fibers at the submicrometer scale. Inside the pores, they blend with the oxidant and begin the polymerization process right there, impregnating the entire material.

The polymerized paper acquires the conductive properties of the polymers. This conductivity can be adjusted by manipulating the element embedded in the cellulose fibers, depending on the application for which the paper is designed. Thus, the device can be electrically conductive, allowing current to flow without significant losses, or semiconductive, interacting with specific molecules and functioning as a physical, chemical or electrochemical sensor.

There’s no mention of a published paper.

Monitoring your saliva via mouth guard and smart phone

I first came across the notion that saliva instead of blood and urine could be used to assess and monitor health in a presentation abstract for the 2004 American Association for the Advancement of Science (AAAS) annual meeting held in Seattle, Washington (as per my Feb. 15, 2011 posting). There have been a few ‘saliva’ health monitoring projects mentioned here over the years but this proof-of-concept version seems like it has the potential to get to the marketplace. An August 31, 2015 news item on Nanowerk features a ‘saliva’ health monitoring project from the University of California at San Diego (UCSD),

Engineers at the University of California, San Diego, have developed a mouth guard that can monitor health markers, such as lactate, cortisol and uric acid, in saliva and transmit the information wirelessly to a smart phone, laptop or tablet.
The technology, which is at a proof-of-concept stage, could be used to monitor patients continuously without invasive procedures, as well as to monitor athletes’ performance or stress levels in soldiers and pilots. In this study, engineers focused on uric acid, which is a marker related to diabetes and to gout. Currently, the only way to monitor the levels of uric acid in a patient is to draw blood.

An August 31, 2015 UCSD news release (also on EurekAlert), which originated the news item, describes the research and the mouth guard in more detail,

In this study, researchers showed that the mouth guard sensor could offer an easy and reliable way to monitor uric acid levels. The mouth guard has been tested with human saliva but hasn’t been tested in a person’s mouth.

Researchers collected saliva samples from healthy volunteers and spread them on the sensor, which produced readings in a normal range. Next, they collected saliva from a patient who suffers from hyperuricemia, a condition characterized by an excess of uric acid in the blood. The sensor detected more than four times as much uric acid in the patient’s saliva than in the healthy volunteers.

The patient also took Allopurinol, which had been prescribed by a physician to treat their condition. Researchers were able to document a drop in the levels of uric acid over four or five days as the medication took effect. In the past, the patient would have needed blood draws to monitor levels and relied instead on symptoms to start and stop his medication.

Fabrication and design

Wang’s team created a screen-printed sensor using silver, Prussian blue ink and uricase, an enzyme that reacts with uric acid. Because saliva is extremely complex and contains many different biomarkers, researchers needed to make sure that the sensors only reacted with the uric acid. Nanoengineers set up the chemical equivalent of a two-step authentication system. The first step is a series of chemical keyholes, which ensures that only the smallest biochemicals get inside the sensor. The second step is a layer of uricase trapped in polymers, which reacts selectively with uric acid. The reaction between acid and enzyme generates hydrogen peroxide, which is detected by the Prussian blue ink.  That information is then transmitted to an electronic board as electrical signals via metallic strips that are part of the sensor.

The electronic board, developed by Mercier’s team, uses small chips that sense the output of the sensors, digitizes this output and then wirelessly transmits data to a smart phone, tablet or laptop. The entire electronic board occupies an area slightly larger than a U.S. penny.

Next steps

The next step is to embed all the electronics inside the mouth guard so that it can actually be worn. Researchers also will have to test the materials used for the sensors and electronics to make sure that they are indeed completely biocompatible. The next iteration of the mouth guard is about a year out, Mercier estimates.

“All the components are there,” he said. “It’s just a matter of refining the device and working on its stability.”

Wang and Mercier lead the Center for Wearable Sensors at UC San Diego, which has made a series of breakthroughs in the field, including temporary tattoos that monitor glucose, ultra-miniaturized energy-processing chips and pens filled with high-tech inks for Do It Yourself chemical sensors.

Here’s a link to and a citation for the paper,

Wearable salivary uric acid mouthguard biosensor with integrated wireless electronics by Jayoung Kim, Somayeh Imani, William R. de Araujo, Julian Warchall, Gabriela Valdés-Ramírez, Thiago R.L.C. Paixão, Patrick P. Mercier, & Joseph Wang. Biosensors and Bioelectronics Volume 74, 15 December 2015, Pages 1061–1068 doi:10.1016/j.bios.2015.07.039

This paper is behind a paywall.

Here’s an image of UCSD’s proposed mouth guard,

The mouth guard sensor offers an easy and reliable way to monitor uric acid levels in human saliva. Credit: Jacobs School of Engineering, UC San Diego

The mouth guard sensor offers an easy and reliable way to monitor uric acid levels in human saliva. Credit: Jacobs School of Engineering, UC San Diego

Nano-Bio Manufacturing Consortium’s request for proposals (RFPs) on human performance monitoring platforms

The requested human performance monitor platform RFPs are for a US Air Force Research Laboratory (AFRL) project being managed by the Nano-Bio Manufacturing Consortium (NBMC), according to a July 17, 2013 news item on Nanowerk,

The Nano-Bio Manufacturing Consortium (NBMC) has released its first Request for Proposals (RFP) focused on developing a technology platform for Human Performance Monitors for military and civilian personnel in high stress situations such as pilots, special operations personnel, firefighters, and trauma care providers. Organized by FlexTech Alliance under a grant from the U.S. Air Force Research Laboratory (AFRL) the RFP comes only 3 month since the group officially formed its technical and leadership teams. The consortium members, working with AFRL, issued this RFP to focus on component development and integration for a lightweight, low-cost, conformal and wearable patch.

The July 17, 2013 NBMC news release, which originated the news item, offers more about this patch/monitor,

The heart of this new patch will be a biosensor device to measure chemicals, called biomarkers, in human sweat.  These biomarkers can provide early warnings of performance issues such as stress, fatigue, vigilance or organ damage.  The platform will contain the sensor, a microfluidic system that delivers sweat to the sensor, printed and hybrid control electronics, interconnects, a power supply, wireless communication, and software – all on a flexible substrate that is comfortable to wear.

“An aircraft has numerous sensors which take over 1500 measurements per second to monitor its condition in flight, whereas the most critical part – the pilot – has no monitors,” Malcolm Thompson, chief executive officer of NBMC stated.  “We are working quickly and efficiently to coordinate the expertise being generated at an array of companies, government labs and academic centers.  NBMC’s goal is to establish this technology chain to more rapidly develop products and manufacturing approaches for the Air Force and commercial markets.”

I gather the reasoning is that we should be able to monitor human beings just as we do equipment and machines.

The news release also offers information about the consortium partners,

Initial consortium membership includes a wide range of organizations.  Fortune 500 technology leaders include General Electric, Lockheed Martin, and DuPont Teijin Films.  More entrepreneurial organizations include PARC (a Xerox Company), MC 10, Soligie, American Semiconductor, Brewer Science and UES.  They are joined by the Air Force Research Laboratory and university leaders such as Cornell University, University of Massachusetts Amherst Center for Hierarchical Manufacturing, University of Arizona Center for Integrative Medicine, UC San Diego, University of Cincinnati, Binghamton University, Johns Hopkins University, Northeastern University NSF Nanoscale Science and Engineering Center for High-rate Nano-manufacturing, and Arizona State University.

The NBMC solicitation was posted July 10, 2013 on this page,

2013 SOLICITATION ON HUMAN PERFORMANCE MONITORING & BIOMARKER DETECTION

Request for Proposals Issued: July 10th, 2013

Proposals Due Date: August 9th, 2013 – 5:00 PM PDT

You can find the 9pp RFP here.

I’ve decided to include this description of the thinking that underlies the consortium, from the NBMC Nano-Bio Manufacturing webpage,

The field of nano-biotechnology is advancing rapidly, with many important discoveries and potential applications being identified.  Much of this work is taking place in academia and advanced research labs around the globe.  Once an application is identified, however, the road is still long to making it available to the markets in need.  One of the final steps on that road is understanding how to manufacture in high volume and the lowest cost.  Often this is the defining decision on whether the product even gets to that market.

With new nano-bio technology solutions, the challenges to produce in volume at low-cost are entirely new to many in the field.  New materials, new substrates, new equipment, and unknown properties are just a few of the hurdles that no one organization has been able to overcome.

To address these challenges, FlexTech Alliance, in collaboration with a nationwide group of partners, has formed a Nano-Bio Manufacturing Consortium (NBMC) for the U.S. Air Force Research Laboratory (AFRL). The mission of this partnership is to bring together leading scientists, engineers, and business development professionals from industry and universities in order to work collaboratively in a consortium, and to mature an integrated suite of nano-bio manufacturing technologies to transition to industrial manufacturing.

Initial activities focus on AFRL/ DoD priorities, e.g., physiological readiness and human performance monitoring. Specifically, NBMC matures nano-bio manufacturing technologies to create an integrated suite of reconfigurable and digitized fabrication methods that are compatible with biological and nanoparticle materials and to transition thin film, mechanically compliant device concepts through a foundry-like manufacturing flow.

The long-term vision is that NBMC operates at the confluence of four core emerging disciplines: nanotechnology, biotechnology, advanced (additive) manufacturing, and flexible electronics. The convergence of these disparate fields enables advanced sensor architectures for real-time, remote physiological and health/medical monitoring.

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[downloaded from http://www.nbmc.org/nanobiomanufacturing/nbm_intro/]

It seems to me that human beings are increasingly being viewed as just another piece of equipment.

Home pregnancy tests inspire simple diagnostics containing gold nanoparticles

PhD student Kyryl Zagorovsky and Professor Warren Chan of the University of Toronto’s Institute of Biomaterials and Biomedical Engineering (IBBME) have created a rapid diagnostic biosensor according to a Feb. 28, 2013 news item on phys.org,

A diagnostic “cocktail” containing a single drop of blood, a dribble of water, and a dose of DNA powder with gold particles could mean rapid diagnosis and treatment of the world’s leading diseases in the near future. …

The recent winner of the NSERC E.W.R. Steacie Memorial Fellowship, Professor Chan and his lab study nanoparticles: in particular, the use of gold particles in sizes so small that they are measured in the nanoscale. Chan and his group are working on custom-designing nanoparticles to target and illuminate cancer cells and tumours, with the potential of one day being able to deliver drugs to cancer cells.

But it’s a study recently published in Angewandte Chemie that’s raising some interesting questions about the future of this relatively new frontier of science.

Zagorovsky’s rapid diagnostic biosensor will allow technicians to test for multiple diseases at one time with one small sample, and with high accuracy and sensitivity. The biosensor relies upon gold particles in much the same vein as your average pregnancy test. With a pregnancy test, gold particles turn the test window red because the particles are linked with an antigen that detects a certain hormone in the urine of a pregnant woman.

(Until now, I’d never thought about how a pregnancy test actually works and always assumed it was similar to a litmus paper test of acid.) The University of Toronto’s Feb. 28, 2013 news release, which originated the news item, describes the technology in more detail,

Currently, scientists can target a particular disease by linking gold particles with DNA strands. When a sample containing the disease gene (e.g., Malaria) is present, it clumps the gold particles, turning the sample blue.

Rather than clumping the particles together, Zagorovsky immerses the gold particles in a DNA-based enzyme solution (DNA-zyme) that, when the disease gene is introduced, ‘snip’ the DNA from the gold particles, turning the sample red.

“It’s like a pair of scissors,” said Zagorovsky. “The target gene activates the scissors that cut the DNA links holding gold particles together.”

The advantage is that far less of the gene needs to be present for the solution to show noticeable colour changes, amplifying detection. A single DNA-zyme can clip up to 600 ‘links’ between the target genes.

Just a single drop from a biological sample such as saliva or blood can potentially be tested in parallel, so that multiple diseases can be tested in one sitting.

But the team has also demonstrated that [it] can transform the testing solution into a powder, making it light and far easier to ship than solutions, which degrade over time. Powder can be stored for years at a time, and offers hope that the technology can be developed into efficient, cheap, over-the-counter tests for diseases such as HIV and malaria for developing countries, where access to portable diagnostics is a necessity. [emphases mine]

I think the fact that the testing solution can be made into powder is exciting news. Medical technologies can be wonderful but if they require special handling and training (e.g., a standard vaccine is in a solution which needs to be refrigerated [that’s expensive in some parts of the world] and someone who is specially trained has to administer the injection) then they’re confined to the few who have access and can afford it.

Here’s a citation and a link to the researchers’ paper,

A Plasmonic DNAzyme Strategy for Point-of-Care Genetic Detection of Infectious Pathogens by Kyryl Zagorovsky, and Dr. Warren C. W. Chan. Angewandte Chemie International Edition DOI: 10.1002/anie.201208715 Article first published online: 10 FEB 2013

Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

This article is behind a paywall.

ETA Mar. 1, 2013 10:42 am PST: I made a quick change to the title. Hopefully this one makes more sense than the first one did.