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SCARCS Calendar:
Today is Friday, 2020-11-27
HF Conditions:
Some Icons by Dryicons
Today is Friday, 2020-11-27
Some Icons by Dryicons
To make your call sign better understood when using voice transmission, you should use the Standard International Phonetics for each letter:
"The Q code is a standardized collection of three-letter codes all of which start with the letter "Q". It is a brevity code initially developed for commercial radiotelegraph communication and later adopted by other radio services, especially amateur radio."1)
There are a lot of them, but here are the ones you'll need to memorize:
|Answer or Statement
|Other Usage
|Is this frequency in use?
|This frequency is in use. Please do not interfere.
|Do you have interference from other stations?
|I have interference form other stations.
|Are you troubled by static?
|I am troubled by static.
|Shall I decrease power?
|Decrease power.
|I'm using low power
|Shall I send more slowly?
|Send more slowly
|Shall I cease or suspend operation?
|I am suspending operation / shutting off the radio
|Have you anything for me?
|I have nothing for you.
|No traffic
|Shall I standby / When will you call me again?
|Please standby / I will call you again
|Who is calling me?
|You are being called by
|Are my signals fading?
|Your signals are fading.
|Can you acknowledge receipt?
|I am acknowledging receipt.
|Same as "Roger"
|Can you communicate with ... direct or by relay?
|I can communicate with ... direct (or by relay through ...).
|A conversation
|Shall I change to on another frequency?
|Change to on another frequency.
|What is your location?
|My location is
A short way to tell another station how well you receive them is to use the "RST" (Readability, Signal Strength, Tone) code. From Wikipedia:
Readability is a qualitative assessment of how easy or difficult it is to correctly copy the information being sent during the transmission. In a Morse code telegraphy transmission, readability refers to how easy or difficult it is to distinguish each of the characters in the text of the message being sent; in a voice transmission, readability refers to how easy or difficult it is for each spoken word to be understood correctly. Readability is measured on a scale of 1 to 5.
1. Unreadable
2. Barely readable, occasional words distinguishable
3. Readable with considerable difficulty
4. Readable with practically no difficulty
5. Perfectly readable
Strength is an assessment of how powerful the received signal is at the receiving location. Although an accurate signal strength meter can determine a quantitative value for signal strength, in practice this portion of the RST code is a qualitative assessment, often made based on the S meter of the radio receiver at the location of signal reception. "Strength" is measured on a scale of 1 to 9.
1. Faint signal, barely perceptible
2. Very weak
3. Weak
4. Fair
5. Fairly good
6. Good
7. Moderately strong
8. Strong
9. Very strong signals
For a quantitative assessment, quality HF receivers are calibrated so that S9 on the S-meter corresponds to a signal of 50 μV at the antenna standard terminal impedance 50 ohms. One "S" difference should correspond to 6 dB at signal strength (2x voltage = 4x power). On VHF and UHF receivers used for weak signal communications, S9 often corresponds to 5 μV at the antenna terminal 50 ohms. Amateur radio (ham) operators may also use a signal strength of "20 to 60 over 9", or "+20 to +60 over 9." This is in reference to a signal that exceeds S9 on a signal meter on a HF receiver.
The strength assessment is a bit tricky when using a repeater because every station using the repeater would appear to your S-metre to have the same strength since you're listening to the repeater, not the individual station. In that case, you have to use a qualitative assessment based on readability more than strength since the other station wants to know how well the repeater is receiving them, not how well you receive the repeater. More on repeaters in the next section.
Tone is only used in Morse code and digital transmissions and is therefore omitted during voice operations. With modern transmitter technology, imperfections in the quality of the transmitter modulation that can be detected by humans are rare. Tone is measured on a scale of 1 to 9.
1. Sixty cycle a.c or less, very rough and broad
2. Very rough a.c., very harsh and broad
3. Rough a.c. tone, rectified but not filtered
4. Rough note, some trace of filtering
5. Filtered rectified a.c. but strongly ripple-modulated
6. Filtered tone, definite trace of ripple modulation
7. Near pure tone, trace of ripple modulation
8. Near perfect tone, slight trace of modulation
9. Perfect tone, no trace of ripple or modulation of any kind
On HF radio, each unit on the S-meter represent a four-fold increase in power, which is 6 dB2). But after S9, the meter shows a dB scale.
For example: "20 over S9" means
So if a station gives you a 20 over 9 signal report when you transmit with 100W, they would still receive you at S9 if you transmitted at 1W. What a power saving!
Here are a few more examples. How many times stronger is station A than station B if:


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One of Africa's finest music group, Sauti Sol comes through with a brand new single, their first of 2020 titled Suzanna.
The record is their first release since the Afrikan Sauce album released in January 2019.
On Suzanna, Sauti Sol tells the story of a wayward lady who has chosen to live the fast life, changing her skin colour and having surgeries to fix a plastic body.
"If you get to hear this song", somebody loves you, change your mind and come back home". Listen to Suzanna by Sauti Sol below:-

subset: commoncrawl


text: Noisebridge and Metalab (in Vienna) were a vital part in the production of our little flick, and it was a pleasure to show it at HOPE in 2014. But now we have a feature-length Christmas present: "Die Gstettensaga: The Rise of Echsenfriedl" is finally online on Vimeo. Enjoy! https://vimeo.com/monochrom/gstettensaga und https://www.youtube.com/watch?v=qjEzckLBazY Cheers, Johannes


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Charles Evans Dual Mandate Responsibilities Speech – Goes Too Far
Yesterday, Charles Evans who is the ninth president of the Federal Reserve Bank of Chicago and a voting member on the FOMC, gave a speech at the European Economics and Financial Center in London. This speech goes too far with starting to push the Fed towards more stimulus as the returns from additional stimulus diminish.…Read More


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Data Engineer
|Job Title:
|Data Engineer
|Contract Type:
|Derby, Derbyshire
|Up to £0.00 per annum
|Contact Name:
|Sean Garbutt
|Contact Email:
|Job Published:
|December 17, 2019 14:14
Job Description
Data Engineer
Derbyshire - Contract
My client is a large organisation within their sector who are going through a large project which looks at their data capabilities and how it can be used to increase the savings it delivers and to allow accurate communication to the customer base.
They require a Data Engineer that has the capabilities to start the development of a new data platform and analytics to support the vision moving forward! This is an exciting and challenging opportunity which gives you the opportunity to really build a substantial data product from the ground up by using the latest cloud & analytics technologies!
Key Skills Required
- Able to work directly and interactively with stakeholders in an agile way
- Data Analysis, Profiling and Modelling - Strong SQL skills
- Data processing using ETL tools (specifically Microsoft technologies)
- Experience of agile projects and project controls
This contract is outside IR35 and is an initial 3 months with scope of extension due to the nature of the project!
If you feel you have the relevant skill-set or want to hear more then please get in touch.
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Pastries, Paninis, & Platters
All of our delicious pastries come from our local bakers. We are able to offer delicious fresh made pastry items that hit everyone's palates just right.
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Try selections such as U of I sausage, Copa, Sopresseta, or Proscuitto. Then nibble on some selections such as Ferdinands cheese, Beechers cheese, Orgeon Blue, or smoked gouda.


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Strictly Come Dancing pairings leak online ahead of BBC return
Strictly Come Dancing fans have been left confused after this year's top secret pairings were leaked online.
The 18th series of the popular BBC show is returning this evening (17 October) with an episode that was pre-recorded earlier this week.
It will reveal which professional dancers are paired with this year's celebrity contestants, including DJ Clara Amfo, EastEnders star Maisie Smith and comedian Bill Bailey.
While it remains unconfirmed whether the source is legitimate, we won't be listings the pairings here as we don't want to spoil the surprise for dedicated fans.
"It was nice not knowing the pairings - that's spoilt Saturday night," one upset fan wrote on Twitter, with another adding: "So allegedly the strictly pairings have leaked online. Thought they weren't having a studio audience this year? I hope I don't come across them, I've been waiting for this series and don't want any spoilers."
One pairing that is strongly expected to become a reality is Olympic boxer Nicola Adams and Katya Jones.
Adams, who has been praised as an LGBT+ role model, told the Daily Star earlier this year that she asked BBC bosses to be partnered with a female professional dancer when she signed up to take part in the show.
"It was important to me because of diversity," she said. "I just wanted to do something different and I didn't get the big deal being paired with another female.
@l3479s So allegedly the strictly pairings have leaked online 🙄 thought they weren't having a studio audience this year? I hope I don't come across them, I've been waiting for this series and don't want any spoilers
— Michelle Pryde (@michellepryde) October 16, 2020
"We go to nightclubs and girls dance with girls all the time and professional female dancers dance with girls all the time, so I don't think it's a big deal."
Strictly Come Dancing returns to BBC One tonight at 7.50pm.
Read more
Nicole Kidman's 10 best performances, ranked
Are Limp Bizkit still the ultimate cultural punchline?
Matt Berninger: 'I mansplain to myself why mansplaining is f***** up'


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Winston-Salem Rescue Team Frees Man Trapped in Flooded Vehicle
Rescuers with the Winston-Salem, North Carolina, Fire Department pulled a man out of a flooded vehicle in the Oldtown area on Thursday, November 12, local reports said.
Video released by the fire department shows rescuers helping a man out of the vehicle and onto his feet in thigh-high water where he was able to walk away. No injuries were reported.
At least seven people were killed in flooding caused by historic rainfall in North Carolina on Thursday. The "widespread flooding also stranded vehicles and rendered some streets completely "impassable," local reports said. Credit: Winston-Salem FD via Storyful


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Aristo Padded Futon Chair
Product Description
|Easily convert this attractive sofa to a bed in seconds. Supported by chrome legs and upholstered in soft leatherette the contemporary style and comfort will add appeal to your home or office. As an added bonus the chair converts to a chaise lounge. Available in four different colors.
Product Features:
Pickup Options:
Fine Furniture Los Angeles offers free local pickup from our warehouse in the City of Industry (Los Angeles area). Our sales team will contact you once your order is ready for free local pick up within 7-10 business days after the order is placed directly on our website. Please note that you will need a truck or a box truck to pick up larger items such as sofas, bedroom sets, etc. Please inspect the item at the time of pick up to ensure that it is in perfect condition. In the event that you discover any damages or defects that require replacement parts, please note that we do require pick up/exchanges of replacement pieces to happen at our Los Angeles warehouse (we cannot ship or mail replacement pieces). We guarantee a perfect product or else we will provide free replacement parts free of cost to our customers. Currently, Fine Furniture Los Angeles does not offer delivery options and can offer local pick up only unless the customer is willing to pay a delivery fee of $250 - $350 depending on the size of the order to ship via LTL freight.
Black Futon Chair
Saddle Brown Futon Chair
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White Futon Chair
Product Q&A
Have a question? Need more information? Ask our staff.
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text: Well, I'm no Tina Turner, but it seems to me that love's got EVERYTHING to do with it. Though if you've listened to the news for even five minutes this past week, I'm not sure you'd know that. Politics, you might easily think, is what it's all about. Or Theology. But LOVE? I haven't heard … Continue reading What's Love Got To Do, Got To Do With It?


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Answers To Your Home Mortgage Questions
To help you secure a good mortgage, you must understand what a loan entails. Do you understand how interest rates work or what the term of a mortgage means? Well, you'll be able to learn a lot from this article so you're able to get yourself a mortgage that you want.
Start the process of taking out a mortgage way ahead of time. If you're thinking about getting a new home, your finances need to be in tip top shape. You have to assemble a savings stockpile and wrangle control over your debt. You will not be approved if you hold off too long.
Have your financial information with you when you visit a lender for the first time. Having your financial paperwork in order will make the process go more quickly. If you have these documents with you, you'll be able to easily apply for your loan in a single trip.
Like most people, you will likely have to have some amount of money for a down payment. Although there are some mortgages you can get without a down payment, for the most part you are required to have one. You need to know your likely down payment before applying.
Your mortgage loan is at risk of rejection if the are major changes to your finances. You should not apply for a mortgage until you have a secure job. If you filled out an application listing your current employer, don't accept a new job until the mortgage is approved.
Become educated about the property taxes on the property you are considering buying. Knowing how much your property tax expense will be can help you make an accurate budget. Your property may be assessed at a higher value than you're expecting, which can make for a nasty surprise.
Just because one company denies you doesn't mean you should stop looking. Even though a lender has denied your application, there are lenders out there that will approve you. Keep shopping around and looking for more options. A co-signer may be needed, but there are options for nearly everyone.
Ask your friends for information on obtaining a home loan. They will probably have some great suggestions and a few warnings as well. A lot of them could have had a bad time with lenders so that you know who you should be avoiding. You'll learn more the more people you listen to.
Think about applying for a balloon mortgage if you think you might not qualify for other loans. It's a short term loan and will be refinanced as soon as the term is up. This can cause you some problems because you may have increased rates which can make it hard on you.
Do your homework about any potential mortgage lenders before you sign an official contract with them. Do not put all of your trust in the mortgage lender. Try finding other clients who have used his lender. Search online. Call the BBB to find out what they say. The more you know going into the loan process, the more money you will potentially save.
Steer clear of variable rate loans. The payments on these mortgages can increase substantially if economic changes cause the interest rate to increase. You might end up having trouble paying your mortgage down the road.
Being upfront and honest about your financial situation is crucial when applying for a loan. If you try to fudge details on your application; you may find yourself denied quickly. If you are dishonest, a lender will not trust you with its money.
Keep your credit score as high as possible to get a good rate. Check your credit report from the 3 bureaus to make sure it is accurate. Any credit score that is lower than 620 is usually denied.
If you want to get a good home mortgage, you have to have a good credit rating. Be familiar with your credit rating. Errors should be corrected on your report and you should do what you can to improve your rating. If you have smaller debts, combine them into one account, with low interest, so you can pay it off quickly.
Before you try to get a home mortgage taken out, be sure everything's in order with your credit report. Good credit is a must. Lenders are looking for a positive payment history and credit worthiness to make sure you will repay your mortgage loan. Tidy up your credit report before you apply for a mortgage.
Before applying for a home mortgage, know how much you want to pay for a home. If you get approved for a loan bigger than what is realistic within your budget, you do get some wiggle room. Always have an idea on what you can afford to spend. Problems in your future could arise if you do this.
Compare multiple factors as you shop for a mortgage. A low interest rate is what you want. Take a look around at various loans available. Think about closing costs, points and other associated expenses when saving money for you home loan.
Look into the appropriateness of a mortgage that lets you pay every other week rather than just once each month. This lets you make two additional payments yearly, which can reduce the interest you pay on the loan greatly. It is a great idea to have payments automatically taken from your account.
When your loan receives approval, you might have the temptation to be a little lax. You must make sure that your credit ratings stay up through the entire process, until that loan is yours. The lender is probably going to look at your credit score and that could occur after a loan is approved. They can still take the loan back if you apply for a new credit card or take on a new car payment.
Figuring out what you need in a mortgage company will help you to get yourself in a good situation. If you are filled with regret about your financial decisions, you will be miserable until you refinance. You can make the best decision your first time around and get comfortable with the mortgage company.


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aMax Planck Institute for Intelligent Systems, Heisenbergstr. 3, 70569 Stuttgart, Germany
bCavendish Laboratory, University of Cambridge, J. J. Thomson Avenue, Cambridge CB3 0HE, UK
cDepartment of Chemistry, University College London (UCL), 20 Gordon Street, WC1H 0AJ London, UK. E-mail: email@example.com
dInstitute for Materials Research and Engineering (IMRE), Agency for Science Technology and Research (A*STAR), Singapore
eInstitute for Materials Discovery, University College London (UCL), UK
First published on 14th May 2019
Gold nanoparticles (Au NPs) are arguably the most versatile nanomaterials reported to date. Recent advances in nanofabrication and chemical synthesis have expanded the scope of Au NPs from classical homogeneous nanospheres to a wide range of hybrid nanostructures with programmable size, shape and composition. Novel physiochemical properties can be achieved via design and engineering of the hybrid nanostructures. In this review we discuss the recent progress in the development of complex hybrid Au NPs and propose a classification framework based on three fundamental structural dimensions (length scale, complexity and symmetry) to aid categorising, comparing and designing various types of Au NPs. Their novel functions and potential for biomedical applications will also be discussed, featuring point-of-care diagnostics by advanced optical spectroscopy and assays, as well as minimally invasive surgeries and targeted drug delivery using multifunctional nano-robots.
Hyeon-Ho Jeong
Dr Hyeon-Ho Jeong is a research associate at the Cavendish Laboratory, University of Cambridge. He received his BEng and MEng in electrical engineering from Dankook University, respectively, in 2010 and 2011. He then moved to Seoul National University Medical Research Centre as a research assistant for a year. In 2017, he received his PhD in Material engineering from Max Planck Institute for Intelligent Systems and Swiss Federal Institute of Technology in Lausanne (EPFL), with two graduate student awards, respectively, from the American and the European Material Research Societies in 2016 and 2017. His research interests include nanomaterials, nanofabrication, and plasmonics.
Eunjin Choi
Eunjin Choi is a PhD student at Max Planck Institute for Intelligent Systems. She received her BSc in Applied chemical engineering from Korea University of Technology and Education in 2014 and MSc in Materials science from University of Stuttgart in 2017. She is currently working on several projects under the supervision of Prof. Peer Fischer at Micro, Nano, and Molecular Systems Lab. Her research interests include acoustic fabrication, organ phantoms, tissue-like materials, and micro actuators with a focus in medical applications.
Elizabeth Ellis
Elizabeth Ellis received her MSci in Chemistry from the University of Bristol in 2014. She is currently studying for a PhD at University College London under the supervision of Dr Tung-Chun Lee, with a two-year research attachment at the Agency for Science, Technology and Research (A*STAR) in Singapore, under the supervision of Dr Xian Jun Loh. Her research interests include the development of self-assembled polymeric nanostructures and hybrid nanoparticles for biomedical applications.
Tung-Chun Lee
Dr Tung-Chun Lee received his BSc in Chemistry from University of Hong Kong in 2005 and his PhD in Chemistry from University of Cambridge in 2012. He was a Post-doctoral Fellow at the Max Planck Institute for Intelligent Systems from 2011 to 2014 before he joined the University College London as a Lecturer and started his independent academic career. His research interests include exotic nanoparticles, nanofabrication, nanochemistry, active matter and supramolecular chemistry. Currently, he is leading an interdisciplinary group of 15 researchers exploring chemistry under nano-confinement, active propulsion at the nanoscale and metamaterial sensors.
Similar to their bulk analogue, Au NPs are well-known for their chemical stability. In particular, they are generally stable against oxidation under physiological conditions (incl. variable pH, ionic strength and temperature) without any major risk of leaching of toxic species.4 Meanwhile, the surface of Au NPs can be easily functionalised by a wide variety of ligands via thiol or amine chemistry. These two properties enable Au NPs to be utilised as an ideal nanoscale platform for drug and gene delivery amongst a range of nanocarriers.5
Nevertheless the key characteristic that distinguishes Au NPs from many other nanomaterials, in the biomedical context, is their unique optical properties resulting from a physical phenomenon known as localised surface plasmon resonance (LSPR),6 which is present typically in nanostructures of plasmonic materials, such as gold, silver, copper and aluminium. LSPR involves coherent oscillation and excitation of conduction-band electrons on the surface of plasmonic nanostructures, such as Au NPs, upon irradiation of light in the ultraviolet-visible-near infrared (UV-VIS-NIR) spectral region.
In the context of light–matter interaction, LSPR is typically stronger than that of small molecules because of a better match in length scale between the travel distance of localised surface plasmon and the wavelength of UV-vis-NIR light and the large polarisability of plasmonic materials at optical frequency. LSPR accompanies optical near-field enhancement that interacts with the medium surrounding a nanoparticle.7 This distinctive optical interaction affects the associated far-field spectral resonance signal and, at the same time, can generate heat locally.8 The strong interaction with light facilitates the use of Au NPs as nano-antennae for revealing optical properties of the nanoscale environment around the nanoparticles, leading to various types of sensing applications,9 as well as for nanolithography,10 photothermal therapy,4 object trapping,11 and nanoscale propulsion via thermophoretic effect.12
The conditions for the occurrence of LSPR are known to be highly sensitive to the three-dimensional (3-D) geometric parameters (e.g. size, shape and symmetry), the material composition and distribution within a NP, as well as the overall arrangement of NPs within an ensemble or array.13,14 In particular, dipolar LSPR of individual spherical Au NPs occurs in the visible region of ∼520–540 nm and can be shifted to the NIR region in the case of elongated NPs (i.e. large shape anisotropy) or assemblies of NPs with nano-spacing. As a result, optical properties of Au NPs (e.g. peak position, bandwidth and the number of resonant modes) can be engineered by designing and optimising structural and material dimensions to suit a specific biomedical application, as illustrated in Fig. 1.
|Fig. 1 Scheme showing functionalities of hybrid Au NPs achieved by engineering their structural dimensions for biomedical applications.
In addition to tailoring the optical properties, incorporation of other functional materials onto a Au NP construct can also introduce other physiochemical properties/functionalities, including magnetism, stimuli-responsiveness, antifouling and cell targeting.15–17 The combination of two or more molecular ligands, polymer coatings and inorganic materials can lead to multifunctional hybrid NPs which can show superior performance in coping with complex biological environments. The facile chemistry in synthesis and functionalisation of Au NPs makes them a promising nano-scaffold for constructing hybrid NPs with multi-functionality.18 Nevertheless, producing bespoke complex shapes with programmable material distribution at the nanoscale remains a challenge because minimisation of surface energy and crystallisation forces generally leads to highly symmetric and homogeneous nanostructures.19
Recent advances in chemical synthesis and 3-D nanofabrication techniques offer new promise in the production of complex hybrid Au NPs in practical quantity and quality. These novel hybrid nanoparticles give rise to multi-functionality which opens up exciting opportunities in their biomedical applications. Unlike previous reviews on Au NPs' synthesis and biomedical applications,2,3,20,21 we here highlight recent development of complex 'hybrid' Au NPs. First, we propose a classification framework for gold nanostructures based on three fundamental structural dimensions (length scale, complexity and symmetry) for classifying and designing novel gold nanostructures. The framework can also be extended to classify other type of NPs. The second part of the review is dedicated to discussing key physiochemical properties exhibited by novel hybrid Au NPs, and their potential biomedical applications, featuring brand-new functions that are unachievable using conventional Au NPs, for instance, direct measurement of blood plasma viscosity at human haematocrit level (ca. 50%) and active drug delivery using self-propelling nanomotors.
With an aim of gaining a clear overview of the highly diverse hybrid gold nanostructures, we propose a classification framework based on three fundamental structural dimensions, namely length scale, complexity and symmetry. Meanwhile gold nanostructures are grouped into three main classes, namely (1) homogeneous Au NPs, (2) heterogeneous Au NPs and (3) Au NP assemblies, according to their length scale and the material's complexity. Representative subclasses can then be organised with respect to each other according to the structural dimensions, as shown in Fig. 2.
|Fig. 2 Hybrid Au nanoparticles. (a) Clusters,47 (b) single crystal nanowire,52 (c) chiral NPs,31,45 (d) core–shell NPs,27 (e) Janus NPs,23 (f) alloyed NPs,142,174 (g) plasmonic meta-molecules,175 (h) DNA-origami templated assemblies,25 (i) large-scale assemblies of NPs.99,176 Adapted by permission from the corresponding references. Copyright American Chemical Society, Springer Nature, Wiley-VCH.
This classification framework can aid comparison and design of nanomaterials in a systematic fashion. While many existing examples of gold nanomaterials are not featured in the scheme owing to limitation of space, other nanostructures can be readily inserted into the framework by benchmarking against examples in the scheme based on the fundamental structural parameters. For instance, Au nanostars are low symmetry and made of pure gold,22 so they can be positioned between rods (Fig. 2b) and helices (Fig. 2c). Detailed discussions on the three main classes can be found in Section 2.4.
The relevance of the structural dimensions to the potential biomedical applications of the nanomaterials and the corresponding consideration about nanomaterials design will be briefly discussed below.
The overall size of a nanoparticle will have major effects on cellular interactions and in vivo pharmacokinetics, including cellular uptake, blood circulation half-life, biodistribution and tumour permeability.24 For prolonged blood circulation half-life, the NPs should be within the size window of 10–150 nm. In cases where rapid renal clearance is desirable, the NPs should be smaller than 10 nm, which is the effective cut-off size of the renal filtration barrier. Within the size window, larger nanoparticles tend to have lower colloidal stability owing to the large van der Waals interactions between them. To screen the attractive interactions and therefore enhance the colloidal stability in aqueous media, coating the surface of nanoparticles with appropriate materials (e.g. hydrophilic small molecules for small Au NPs, highly hydrophilic polymers or inorganic materials for large Au NPs) is generally required for most in vitro and in vivo applications.
The purpose of incorporating other materials and molecular components in a gold nanostructure is to address basic design requirements of the service life cycle of a given biomedical application, as well as to introduce multiple functionalities within a single nanostructure.
Service life cycle design is particularly crucial for in vivo applications. In addition to considerations on NP size discussed in Section 2.1, a number of requirements, many of them non-negotiable, have to be fulfilled when designing hybrid Au NPs. For instance, the NPs have to be water-soluble, colloidally stable and biocompatible. On top of that, the NPs have to perform the pre-defined function specifically and efficiently. Since biological systems are highly complex in nature, the ideal NPs will need to cope with the complex environment while being transported to the target region and trigger a specific task on-demand. This can only be achieved by incorporating and optimising multiple functionalities from various functional molecular, polymeric and material components on the NP platform.
Furthermore, entirely new properties and functions can arise by carefully combining functional materials. For instance, forming the Pt layer surrounding Au NPs permits detection of p24, one of the earliest and most conserved biomarkers of human immunodeficiency viruses (HIV), via lateral flow immunoassay in 20 min with 104–105 of the molecular dynamic range (roughly two-fold larger than the commercial products).26 This is not possible with either material alone.
The production of hybrid Au NPs can be achieved by various approaches. The simplest route is via a linear series of stepwise reactions, such as the formation of core–shell nanostructures by growing a layer of material around the Au NP core (Fig. 2d).27,28 The shell layer can then be further functionalised by another material or ligand. However, the level of complexity and structural diversity can be limited by the yield of each step in the series. This issue can be overcome by using either a convergent approach or a divergent approach, both of which have been commonly used in synthesis of complex organic molecules.
The convergent approach involves the synthesis of individual components, followed by the combination of all individual components to form the final product. This is an effective way to increase the degree of complexity of a nanostructure without compromising the synthetic yield. Supramolecular self-assembly is often employed in the final step of combining individual components because of its mild reaction conditions and the tendency to reach the desired state of thermodynamic equilibrium via dynamic exchange of supramolecular bonds. The latter is particularly important to the successful formation of highly complex structures which is prone to inhibition by kinetically trapped states. For instance, the synthesis of DNA-origami templated assemblies (Fig. 2h) was typically performed via the preparation of functional Au NPs and the DNA-origami scaffold, followed by the combination step via aqueous self-assembly.25
The divergent approach involves the initial synthesis of an intermediate which can subsequently be converted into a wide range of nanostructures. This approach can efficiently produce a library of chemically or structurally related nanostructures. Examples include structurally similar Au nanocages from Ag nanocubes,29 as well as Au NPs coated by a mixed self-assembled monolayer with various ligand composition from surfactant-stabilised Au NPs.30
On top of the above approaches, the conflict between yield and complexity of hybrid Au NP synthesis can be tackled by fundamentally developing fabrication techniques with (close to) quantitative yield. For instance, nanoscale glancing angle deposition (nano-GLAD) is a novel 3-D nanofabrication technique that allows direct growth of hybrid Au NPs (and other nanostructures) in a parallel manner, producing Au NPs with high degree of complexity of a practical amount.31,32 In contrast, dip-pen lithography, which is a nanoscale printing technique, can be used to fabricate increasingly complex hybrid NPs, but the throughputs remain insufficient for the practical use.33,34
For a given symmetry, the aspect ratio of a nanostructure describes the ratio between the length of the structure along the principle axis (i.e. that of highest rotational symmetry) to the width perpendicular to the principle axis. The aspect ratio is reflected as the shape factor χ in the Mie solution to the Maxwell equation, where the conditions of a particular LSPR mode are given as εr = −χεm.7 Here, εr is the real dielectric constant of metal NP and εm is a refractive index of the surrounding medium. For sphere, χ = 2 while for rod >2. It is noted that LSPR can be red-shifted to the NIR range with increasing shape factor (i.e. aspect ratio) of the nanostructure, which can be useful for in vivo applications due to the long penetration depth of NIR radiation through skin and tissue. Moreover, sensitivity of a plasmonic sensor also increases with the shape factor and thus the resonance wavelength of the LSPR mode (Section 3.1.1); meanwhile background fluorescence generally decreases with increasing excitation wavelength in surface-enhanced Raman scattering measurements (Section 3.1.2). Both of these cases benefit from shifting the LSPR to the NIR regime. Nevertheless, the use of NIR light accompanies a reduction in spatial resolution of the sensing probe, as well as expensive and complex optical settings. Therefore, optimisation based on case-specific design constraints is often required in practical scenarios.
Decreasing the symmetry of a nanostructure can give rise to interesting optical effects. In particular, a nanostructure is classified as chiral if it falls into any of the low symmetry point groups without a plane of symmetry (C1, C2, C3, D2, D3). As the shape of chiral Au NPs (Fig. 2c) cannot be superimposed onto its mirror image by simple rotation or translation, they exhibit chiroptical effects near the frequency of the LSPR. Despite the presence of analogous chiroptical effects in pure enantiomers of chiral small molecules, chiroptical effects originated from LSPR are typically orders of magnitude more pronounced because of their strong light–matter interaction. As a result, chiral Au NPs find potential applications in background-free optical sensing in optically dense bio-media (Sections 3.1 and 3.3), as well as environmental toxins in complex sample mixtures such as soil.
Another unique property of chiral NPs is the strong coupling between rotational and translational motion in fluid media. For instance, when a helical NP is rotating unidirectionally around its long-axis, it can produce linear propulsion force and translate in a single direction through a fluid, despite the presence of strong Brownian forces at the nanoscale. Furthermore, this type of rotation breaks the time-reversal symmetry of the system, and therefore enables the helical NP to propel through media at the low Reynolds number regime, which is a scenario when viscous forces dominate over inertia and is common among micro- and nanoscale systems. This propulsion strategy has been used by microorganisms, such as E. coli (Escherichia coli), found in nature for millions of years, but has been demonstrated in artificial micro-/nanosystems only in recent years.35 The exciting possibilities of generating and controlling propulsion forces down to the nanoscale promise a wide range of novel applications, spanning minimally invasive surgery and active drug delivery (Section 3.2 and 3.3).
Nevertheless, synthesis and fabrication of Au NPs (and other nanostructures) of low symmetry, especially with well-defined chirality, remains a tremendous challenge, because energetically favourable geometry at the nanoscale generally exhibits a high degree of symmetry owing to minimisation of surface energy and crystallisation forces.
While it is difficult to synthesise NPs of a chiral shape, classical attempts of investigating chiroptical effect of LSPR relies on the attachment of enantiomerically pure chiral small molecules onto the surface of Au NPs. After functionalisation, the Au NPs are effectively surrounded by a chiral medium, which will induce chiroptical effects, such as circular dichroism, around the LSPR signal of the Au NP. However, the induced chiroptical effects in the LSPR are typically weak.36–38
Other chemical approaches were developed to achieve direct chiroptical effects of LSPR. One effective route is to attach via supramolecular self-assembly Au NPs around chiral molecular templates which are available from natural sources or organic synthesis. Various chiral molecular templates, including amino acids, double-strand DNA and DNA-origami, have been investigated regarding their effectiveness on mediating the formation of chiral assemblies of Au NPs.25,36,39–41 Notable success has been attained by using DNA-origami scaffolds owing to their versatility and precision in forming into a wide range of programmable 3-D shapes. Another route towards chiroptical LSPR is to directly grow Au NPs into chiral shapes or with chiral imprints by solution-based synthesis. This can be achieved by growing Au NPs in the presence of chiral-directing agents. Despite being demonstrated in NPs of a few other materials,42–44 chemical synthesis of chiral Au NPs has not been reported until very recently.45
On the other hand, physical methods, mostly electron-/ion-beam-based lithography, have also been used for the fabrication of diverse 2.5-D and 3-D chiral nanostructures.46 These methods can be used to make chiral structures with interesting chiroptical properties, but they often do not permit large (wafer-) scale processing. Yet the possibility of wafer-scale fabrication of chiral Au NPs has been recently demonstrated using a novel nanofabrication technique (nano-GLAD).31 Furthermore, the resultant chiral Au NPs (Fig. 2c) can be easily detached from the wafer surface to form stable nanocolloidal solutions of a practical concentration (1010 NPs per mL), shedding light on their potential applications as solution-based chiral LSPR biosensors (Section 3.1).
At the low end of the length scale, Au clusters and nanoclusters (Fig. 2a) are typically smaller than 5 nm, and exhibit weak or no LSPR effects. They are traditionally synthesised from organometallic precursors that require stringent control over reaction conditions.47 Recent advances of micro-reactor technology allow them to be made via facile flow synthesis.48,49 Au clusters have been shown to have excellent antimicrobial activity.50,51
Moving up along the length scale (5–100+ nm), there exist a wide variety of Au nanocrystals with different shapes (Fig. 2b),52 ranging from the classical spheres to cubes, plates, rods, wires and stars. Anisotropic shapes with a large aspect ratio can shift the LSPR to NIR wavelength which could be beneficial for in vivo applications.
Moving down the symmetry dimension, there are chiral Au NPs (Fig. 2c) which show unique chiroptical properties around the LSPR wavelength.31,45
When the core is only partially coated on one side or coated by a different material on each of the two faces, then it will lead to a break of mirror symmetry on the NP, forming Janus NPs (JNPs, Fig. 2e) which are named after the two-faced ancient Roman god. The break of mirror symmetry, when coupled to an appropriate mechanism, can lead to interesting phoretic effects, such as self-electrophoresis in Au–Pt JNPs54 and thermophoretic effect in Au–SiO2 JNPs55 and thermophoresis in Au–DNA JNPs.56 As a basic asymmetric NP, JNPs can also serve as key intermediates towards more complex asymmetric NPs, such as Au NP@SiO2 nanocups.57,58
At the higher end of the complexity dimension, heterogeneous Au NPs can consist of multiple materials (including metals, alloys, ceramics, magnetics and polymers) with different material composition and distribution, which are broadly classified as hybrid Au NPs (Fig. 2f).59–61
Metamolecules are discreet assemblies made of a small number (<50) of Au NPs (Fig. 2g).62 This category embraces the simplest forms of NP assemblies (e.g. dimers, trimers, tetramers) which in some cases resemble the shape of small molecules. Typically, they can confine light between their gaps, leading to strong optical field enhancement.63 The enhanced optical field can be coupled to vibration of molecules within the gaps and thus making it possible for them to be detected at the single molecular level (Section 3.1.2).
DNA-templated assemblies reside in the higher end of the complexity axis (Fig. 2h). They have a relatively long history, but their development has recently reached a new height, thanks to the DNA origami techniques which can produce highly sophisticated templates for specific attachment of Au NPs.64 Their potential applications in the biomedical area are, however, limited by the abundance of deoxyribonuclease (DNase) in the human body that efficiently catalyses the hydrolytic cleavage of phosphodiester linkages in the DNA backbone, thus degrading the DNA scaffolds.
Large scale Au NP assemblies (a.k.a. aggregates) can reach a millimetre in size (Fig. 2i). They are often formed by controlled aggregation of Au NPs in solution, mediated by gold-ligand bonding,65–68 supramolecular complexation59,69 electrostatic interactions,70 and bio-polymers/objects (incl. proteins, peptides and viruses).64
|Fig. 3 Plasmonic extinction spectroscopy. (a) Schematic view of plasmonic sensing. Top panel shows the plasmonic resonance of metallic nanoparticles as a function of wavelength. Inset shows a metallic nanosphere interacts with light and generates a detectable absorption peak due to LSPR. The bottom panel shows a zoomed-in region near the peak, illustrating how it shifts in wavelength as the refractive index of the surrounding medium changes n1 < n2. (b) Sensitivities of plasmonic NPs reported in the literature as a function of the peak wavelength in water. The symbols and colours are different for the shapes and the material composition respectively (Au sphere,80 Au cube,80 Au rod,80 Au bipyramid,80 Au prism,177 Au star,80,178,179 Ag sphere,180,181 Ag cube,182,183 Ag prism,180,184,185 core/shell (or shell),186–190 and Ag–Ti nanohelices85). (c) Circular dichroism (CD) spectra of Ag–Ti nanohelices in media of five different refractive indices (red: 0%, orange: 5%, green: 10%, blue: 15% and violet: 20% glycerol–water mixtures) over the full spectral range. Inset shows the TEM image of a single Ag–Ti nanohelix (scale bar 50 nm). The bottom panel shows a detailed plot of the resonance shifts at zero-crossing. The filled curves represent |CD|−1. Adapted from ref. 85 with permission. Copyright 2016 Springer Nature.
An elegant way to approach this problem is to introduce shape chirality to the NPs (as discussed in Section 2.3, from left to right in the framework in Fig. 2). This allows the observation of feature-rich plasmonic signals supported by chiral Au NPs using standard chiroptical spectroscopy.31 For instance, chiroptical LSPR response can be monitored by circular dichroism (CD) spectroscopy, which measures the differential extinction of the chiral NPs with left- and right-handed circularly polarised light (Fig. 3c, see also Section 3.1.3).88 The observed signals possess information about the bipolar nature of CD, from which richer spectral features and zero crossings can be extracted and analysed to yield a narrow effective FWHM and thus high FOM data (lower panel of Fig. 3c).85,89 A proof-of-concept immunoassay based on biotin–avidin binding has been demonstrated using CD spectroscopy on functionalised Ag–Ti nanohelices.85 Strictly speaking, here change in the CD spectra is due to the change in n according to the molecular binding on the NPs and unnecessary to involve chirality of molecules (see Section 3.1.3 for chiral molecule sensing). Similar approaches with plasmonic meta-surfaces have been demonstrated in conjunction with magnetic anisotropy,90 Fano-type resonance,91 or polarisation dependent spectroscopy.92 They can increase the sensitivity and FOM, but their mechanisms rely on surface interactions requiring an array of nanostructures, thus limiting modular sensing schemes for in vivo applications.
|Fig. 4 Plasmonic vibrational spectroscopy. (a) Illustration of a target molecule in the 'glue' molecule in the nanoparticle-on-mirror geometry (top panel). The bottom panel shows the simulated near-field of the coupled gap plasmon.94 (b) Anti-Stokes/Stokes spectra at a time when additional picocavity-induced lines are present. Colours correspond to same lines on Stokes and anti-Stokes sides, with vibrational eigenmodes and effective temperatures shown.63 (c) Left panel shows the TEM image of Au NPs aggregation with 'glue' molecules. Inset shows the associated numerical simulation of field enhancement.66 The middle panel shows the SEM image of the self-assembled gold nanorods (inset: its photo in bulk).99 Right panel shows a photo of an on-site SERS measurement using the smartphone-based Raman spectrometer.105 (d) Multi-reflection spectra of plasmonic antennas revealing the signal deformation according to lipid membranes and protein molecules in the enhanced optical field (top panel).106 Bottom panel shows low loss dielectric meta-pixels that overcome intrinsic metal losses, converting absorption signatures into barcode-like molecular images.108 Adapted by permission from the corresponding references. Copyright Spring Nature, American Association for the Advancement of Science, American Chemical Society, Royal Society of Chemistry.
In contrast, SEIRA signals from ultra-small sample volumes can be achieved by overlapping the plasmonic resonance with the absorption bands of targeted molecules (Fig. 4d).95 The resonance mode of the plasmonic antenna can be used to confine the IR right into the nanoscale volume, and can be engineered to overlap with the vibrational signatures of target molecular absorption bands. This allows for simultaneous SEIRA enhancement and detection. Crucially, compared to SERS that necessitates extremely short detection length, SEIRA can still be functional up to several hundred nanometres, making this ideal for the multi-length scale detection ranging from sub-nanometre CO molecules to proteins and lipid membranes over several tens of nanometres.106,107 In particular, this technique is expected to be key for understanding the role of protein misfolding in incurable neurodegenerative disorders including Alzheimer's and Parkinson's diseases.95 Recently, with an advanced material perspective (from upper-left to lower-right in the framework in Fig. 2h), the barcode-like molecular 2-D imaging based on low loss dielectric SEIRA structures has been developed.108
Chiral plasmonic NPs (on the right side of the framework in Fig. 2) promise new sensing schemes that permit the detection of chiral molecules. Since their structural dimensions approach the wavelength of visible light, they give rise to strong chiroptical effects in the visible range of the spectrum.46 Impressively, a colloidal solution of chiral NPs show not only several orders of magnitude stronger chiroptical effects than those exhibited by chiral molecules, but also non-linear optical activity, which is not possible to observe from chiral molecules.113 We here introduce two representative sensing schemes of chiral molecules using hybrid Au NPs, namely superchiral sensing and chirality transfer. Note that while the former requires chirality of both molecule and NP, only chiral molecule is necessary for the later (i.e. no chiral NP). The former employs the optical field near a chiral plasmonic NP (at the right-corner of the framework in Fig. 2). Such chiral near-field supported by chiral NPs can give rise to an optical chirality surpassing that of circularly polarised light, known as a superchiral field.114 This is suggested to distinguish the chiral molecule in the chiral near-field,115–117 but the underlying mechanism of how the chiral near-field may interact with the chiral molecule and affect the far-field CD spectrum is still under debate.36 On the other hand, the approach of chirality transfer utilises Förster-type resonance energy transfer (FRET) with plasmons.118 During plasmonic resonance, an achiral NP (i.e. high symmetry at the top-left corner of the framework in Fig. 2) generates a 'hot electron', which is the metastable state of excited electrons, but has no visible optical activity itself. If this plasmonic NP is in contact with a chiral molecule, energy can be transferred to the molecule such that the molecular optical activity can be stimulated.119 This could be a flexible and sensitive sensing scheme and recently Raman optical activity (ROA) has been enhanced in this way,120 which is analogous to SERS but potentially offers the fingerprinting of molecules in 3-D. They however show yet inherently low signal to noise level, and therefore require extremely active plasmonic NPs to enhance the signal. This challenge might be overcome by using hybrid NPs in the near future.
|Fig. 5 Plasmonic heating for therapy. (a) Hybrid gold nanomaterials loaded with human cells for target delivery and enhanced photothermal therapy.124 Left panel shows the TEM image of the Au core–shell NPs. (b) Photosensitiser-loaded plasmonic gold vesicles for trimodality (fluorescence, thermal, and photoacoustic imaging) guided photo-thermal and dynamic cancer therapy.125 (c) NIR-light-induced DNA release.129 A continuous light irradiation causes dehybridisation and release of fluorescently tagged single-stranded DNA (ssDNA), while pulsed irradiation results in Au–S bond breakage and release of double-stranded DNA (dsDNA). Adapted by permission from the corresponding references. Copyright American Chemical Society.
|Fig. 6 Advanced target delivery using plasmonics. (a) Distribution of free Au NRs and neural stem cell (NSC)-aided Au NRs after 3 days of intratumoral injection.131 (b) Positioning and injection of functionalised plasmonic JNPs into cells.135 Left panel shows the SEM micrograph of a JNP consisting of a spherical Au NP (∼80 nm) connected to a dielectric alumina shaft (length: ∼500 nm). The Al2O3 part of the JNPs is functionalised with a fluorescently labelled oligo-ssDNA. Adapted by permission from the corresponding references. Copyright American Chemical Society.
|Fig. 7 Active nanorheology using plasmonics. (a) A schematic of a rotating nanomotor sensor.139 (b) HR-TEM image of a Au/Fe/Au nanorod and its corresponding elemental false-colour mapping images. (c) FFT plots of the extinction signals of the Au/Fe/Au nanoprobes under a magnetic field rotating at 3.33 Hz (black: bare probe, red: probe with antibody, blue: probe with antibody-antigen reaction).140 (d) TEM image of the 2-turn Au–Fe nanohelix with ca. 170 nm in height. Schematic depicting a rotating magneto-plasmonic nanoprobe in a complex and optically dense medium (here blood plasma surrounded by erythrocytes). (e) In situ active nanorheology in blood. The top panel shows the extinction and CD spectra of the colloidal Au–Fe nanohelices as a function of wavelength in bovine blood plasma surrounded by the erythrocytes at different volume fractions (top, 0%; middle, 33%; bottom, 50%). The bottom panel shows the measured dynamic viscosity of the bovine blood plasma in the presence of red blood cells with different hematocrit level.142 (f) Schematic of the Co/Au nanodomes with out-of-plane magnetisation (left panel). The right panel shows HR-TEM image of the nanodomes with the Co/Au multilayers.23 Adapted by permission from the corresponding references. Copyright Wiley-VCH, American Chemical Society.
The switching property is a crucial basis for their use as nanomechanical probes. Under the rotating magnetic field with frequency fB, viscous drag causes a phase lag ϕ between m and B, which is fixed to its orientation. In the steady state, ω = 2πfB, the balance of torques means that the phase angle is related to the drive frequency according to144
On the other hand, if the probe is protected from any surface interaction (i.e. no change in S), then viscosity becomes a sole variable affecting ϕ and can be measured by tracking ϕ. This is particularly interesting when the nanoprobes are in the complex fluids containing a mixture of multiple phases.146 In fact, since many biological systems fall into this category, this becomes an important consideration for medical applications. Typically, biological complex systems possess a solid phase (e.g. micro-particles and cells or a network of macromolecules) dispersed in a fluid phase, so their macroscopic rheological measurements generally show non-Newtonian viscoelastic behaviour although the liquid phase alone is a simple Newtonian fluid.147 It is therefore impossible to measure using conventional macroscopic rheometers the rheological property of the liquid without first isolating the liquid phase from the complex media. However, local measurement of the fluid viscosity can be possible if the total length of the probe is in the nanoscale, which is smaller than the mesh size of the network or the space between the micro particles.148–150 In this case, dynamics of the nanoprobes can be decoupled with the dispersed phase, and can be therefore used to measure their surrounding fluidic viscosity, even within complex fluid media.142
There exist additional considerations in performing optical measurements in complex media. Optical signals can be hugely attenuated and perturbed by the absorption and scattering of the dispersed solid phase. This explains why it is extremely challenging to extract meaningful optical signals from any optical probes in whole human blood which contains a high level of highly light-absorbing red blood cells. Hence conventional optical sensing is performed in blood plasma without any cells. For direct optical measurement in complex media, innovative approaches are needed to generate optical, spectral or phase contrast against a complex and strongly attenuating background. When coupled with a modulating external magnetic field, polarisation-dependent optical properties of anisotropic NPs can be employed to generate phase contrast in the frequency domain. This approach has been employed in gyromagnetic imaging. Identification and tracking of Au nanostars with a magnetic core inside tumour cells were achieved using broadband excitation.151 Moreover, this approach can be extended by using chiral NPs of Au–Fe (Fig. 7d). In particular, the CD signal of Au–Fe nanohelices is background-free as it is insensitive to achiral objects. External magnetic modulation of these magnetic nanohelices allow the direct measurement of blood plasma viscosity in whole blood (optical density of ∼3, Fig. 7e).142 This scheme can be further applied to fluids with non-Newtonian properties such as living cells.152
|Fig. 8 Micro-actuators with plasmonic trapping. (a) Schematic showing the injection of the helical micro-actuators inside the eye and actuate them via the external magnetic field.166 (b) Integration of plasmonic NPs with the helical micro-actuators.167 (c) Schematic depicting how the micro-actuator with plasmonic trapping can be functional for active cargo delivery. The bacteria can be trapped and released by light and their actuation can be controlled independently by external magnetic field. (d) Corresponding experimental demonstration. Adapted by permission from the corresponding references. Copyright American Association for the Advancement of Science.
The development trend of Au NPs in academia can be reflected in the number of publications containing this and other closely related key words (Fig. 9a). Overall this area of research is booming with number of publications reaching 104 per year. It is interesting to note, however, that the share of Au NPs within the NP literature is slightly declining over the past decade, accompanied by the raise in the share of hybrid Au NPs within the Au NP literature (Fig. 9b). This observation indicates that the focus of the field is shifting towards the development of complex multicomponent NPs.
|Fig. 9 Growing popularity of hybrid gold nanoparticles. (a) Number of academic articles published containing the terms of nanoparticles (NPs, black), gold nanoparticles (Au NPs, orange), hybrid NPs (red), and hybrid Au NPs (green) since 1994. (b) Possession rate of Au NPs vs. NPs (orange), hybrid NPs vs. NPs (red), and hybrid Au NPs vs. Au NPs (green). Source: Web of Science, as assessed on February 1st 2019.
The rapid and diverse evolution in the hybrid Au NPs motivates us to shape a new classification framework of the hybrid Au NPs based on their fundamental dimensions (length scale, material complexity, and symmetry, Fig. 2). Categorisation systems such as this could help demystify the wide range of materials available and provide a systematic tool for designing new nanomaterials. In the practical aspects, the framework can facilitate convenient comparison and benchmarking of novel Au NPs against well-established Au NP systems. Moreover it could also aid reflection on the future direction of Au NP research with regards to the balance between exploring complex new materials and exploiting well understood existing materials in both fundamental and practical contexts.
In the latter part of the review, we have discussed how the novel physiochemical properties of hybrid Au NPs can potentially be translated to clinical applications, illustrated by recent proof-of-concept examples in biosensing, photodynamic therapy, gene & drug delivery, nanorheology and minimally invasive surgery.
Despite the huge volume of research on the topic (as seen in Fig. 9), the number of Au NP systems finding their way into clinical trials (or other general use) remains insignificant.168 Currently, in vivo use of Au NPs have not been approved by the Food and Drug Administration (FDA).169 Approval of clinical use of hybrid Au NPs will be even more challenging to obtain, because the combined toxicity from other components is often hard to characterise in the human body. Encapsulating the hybrid Au NPs within an inert shell (including PEG170 and silica20) might provide an effective solution,60 but their body clearance mechanism is still not fully elucidated, leaving potential risk of bioaccumulation and chronic toxicity. Nevertheless, hybrid Au NPs could find easier translation in in vitro applications. Novel plasmonic sensing schemes (Section 3.1) can be readily implemented in and enhance the capabilities of existing point-of-care technologies, including LFA and hand-held SERS biosensors.
To accelerate the translation and deployment of hybrid Au NPs and the corresponding technologies in the biomedical context, the field calls for cheap, decentralised and high throughput approaches for toxicity screening and intracellular detection of nanomaterials.171 Standard operating procedures (SOPs) of testing should be established within the scientific community and test results should be stored in open-access databases supported by social enterprises or governments initiatives.
On the front of fundamental science, it might be interesting, and perhaps useful, to perform systematic studies on biocompatibility and pharmacokinetics of hybrid Au NPs at the cellular, tissue and animal level, with an aim to extract high-level insights into how hybrid Au NPs interact with biological systems compared to the corresponding individual components. This type of work will benefit from state-of-the-art characterisation techniques. For instance, liquid-cell transmission microscopy (LC TEM)172 emerges as a powerful technique for mapping Au NPs within a living cell with unparalleled spatial resolution. Meanwhile optical microscopy based on non-linear optics, e.g. pump–probe four-wave mixing imaging,173 offers a promising avenue towards in situ 3-D tracking of single NPs with impressive spatiotemporal resolution.
|This journal is © The Royal Society of Chemistry 2019


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Being a "never Pro" buyer, I'm more than a little concerned about the mini balls on the lower playfield. I wish someone had leaked this information so it didn't come as such a shock! The mini balls on Shrek/Family Guy were awful. This mini playfield seems to have a better layout and ramps than Donkey, but still... I will definitely have to play this one to make up my mind. The rest of the game looks awesome and the music track is awesome! Munsters is my favorite TV theme song ever. The lighting, ramps, Herman toy, call outs, etc look great and so does the display. I also like the window to the lower playfield being screwed in like the ACDC VE was. This is much better solution than making it a part of the playfield with clear coat over it. The orbits look smooth as glass and the game doesn't seem to be a drain monster out the sides.
Edit: The black and white version looks way better than I expected! Maybe I shouldn't worry about the mini balls on the lower playfield so much haha.


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