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Picture of a human melanoma cell line growing in tissue culture

High-resolution multi-omics profiling of individual cells

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In a landmark publication, Tian et al. demonstrate the feasibility of combined GCIB/C60 SIMS imaging for multi-omics profiling in the same tissue section at the single-cell level.

A new approach

Multi-omics data are vital to understanding normal regulatory processes and are essential for designing new anti-cancer modalities. Unfortunately, sample preparation methods between different omics are typically incompatible. As such, it is nearly impossible to correlate multiple omics profiles within the same sample, let alone their spatial co-localisation at the single-cell level.

The new approach developed by Tian et al. thus represents a significant leap forward.

The study, reported in the journal Analytical Chemistry, uses a multimodal approach using the J105 SIMS to correlate different cell types. First, water cluster SIMS maps the lipids and metabolites in individual cells. Then, multiplexed SIMS imaging with a high-resolution C60 beam maps the same tissue section stained by lanthanide tagged antibodies.

Close up picture of a microscope

Multiplexed SIMS imaging involves linking specific lanthanide isotopes to antibodies and applying them to the tissue. Subsequent SIMS imaging of the lanthanides maps multiple cellular epitopes at sub-cellular resolution.

The combined approach of water cluster SIMS plus multiplexed ion beam imaging on the same tissue section enables mapping lipids, proteins, and metabolites at the single-cell level.

High-resolution multi-omics

Cryogenic water cluster SIMS was conducted on the J105 SIMS at 1.6-micron beam spot size on fresh frozen sections of invasive ductal carcinoma/ductal carcinoma in situ (IDC/DCIS) tissue. This analysis was followed by staining with lanthanide-tagged antibodies on the same frozen-hydrated tissue and imaging the same region using a C60 beam with a 1.1 µm spot size.

Workflow schematic. The frozen-hydrated IDC/DCIS sample is first analysed using water cluster SIMS with a 1.6 µm spot size. The sample is then stained with lanthanide-tagged antibodies and imaged with C60-SIMS with a 1.1 µm spot size. Image reproduced from Anal. Chem. 2021, 93, 23, 8143-8151.

The first results

Water cluster SIMS revealed the distributions and intensities of more than 150 lipids and important metabolites up to m/z 2000. HCA analysis revealed considerable variation between the location of cluster SIMS identified ions and the nine C60-SIMS cell markers.

This work represents the first successful attempt to profile proteins, lipids, and metabolites on the same tissue at the single-cell level. GCIB-SIMS, especially water clusters, has demonstrated its unique ability to detect lipids and metabolites in biological samples at unprecedented resolutions.

Picture of a person placing a sample into the J105 SIMS

Using a combined SIMS imaging approach enables the correlation of different cell types with their metabolic and lipidomic status. It offers valuable information about proteins, lipids, and metabolites on the same sample and at the same resolution.

The J105 SIMS provides a unique platform for this multimodal SIMS approach. The only instrument to offer water cluster SIMS plus multiplexed ion beam imaging, the J105 also provides high mass accuracy and tandem MS capabilities for accurate ion assignment.

Read the complete publication here.

Experience the capabilities of the J105 SIMS for yourself by booking a demonstration. Get in touch with our sales team today to organise your demo.

Q-One Ion ColumnIonoptika

New funding boosts the UK’s future in Quantum manufacturing

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Q-One single ion implantation

Ionoptika Ltd and the University of Surrey have been awarded project grants worth a total of £425,000.00 from Innovate UK, the UK’s innovation agency, to expand their research into new manufacturing technologies for quantum devices.

Quantum technologies are expected to create impact across multiple sectors from more secure online communications to personalised medicine. However, to date only a handful of companies, such as IBM and Google, have successfully built a basic quantum computer because of the extreme challenges to manufacture and operate these devices. This new Innovate grant will open up new scalable manufacturing methods to researchers in the UK and around the world.

The project, entitled “Rapid and Scalable Single Colour-Centre Implantation for Single Photon Sources”, was recommended for funding by a panel of independent assessors, who concluded that “This is an innovative project by two expert partners. If it is successful, it will lead to a unique product that may possibly revolutionise quantum computing.”

Ionoptika Ltd, together with the University of Surrey, will use beams of ionised atoms to create quantum devices one at a time using rare earth elements such as erbium and ytterbium. Ion beams are used widely in the scientific and manufacturing sectors, from the production of computer chips to medical diagnostic instrumentation and cancer treatment.

The technique, known as ion implantation, has been used for decades to make modern computer chips and benefits from being much quicker than other manufacturing methods. The main limitation of the technique for quantum applications has been the inability to precisely control the location and numbers of implanted ions at the single-ion level. The new tool from Ionoptika, called Q-One, solves this problem yet is still fast enough to implant one thousand quantum bits (qubits) every second.

Q-One Single Ion Implantation

The funding comes on the back of $1.3bn in UK government funding allocated for quantum technologies research.1 It is expected to help Ionoptika expand, creating 20+ highly skilled STEM jobs in the Southampton area over the next 5-10 years, and injecting £6m+ into the UK engineering supply chain.

Paul Blenkinsopp, Managing Director at Ionoptika, commented, “Quantum technologies are set to drive the next generation of innovation and technologies. Ionoptika is delighted to be working with the University of Surrey on developing the tools and infrastructure that will be needed to realise many of these exciting quantum applications.”

Dr David Cox, from the University of Surrey, added, “The University of Surrey through the National Ion Beam Centre is delighted to work on this project with Ionoptika. The ability to precisely control the implantation of ions at the single-atom level offers enormous potential to the newly emerging quantum technologies that are set to revolutionise the world.”

Press release: pressat.co.uk/releases/new-funding-boosts-the-uks-future-in-quantum-manufacturing-766391c0ab7bf7129d63a0993739e010/

Ionoptika, a UK SME based in Chandler’s Ford, Hampshire, has driven innovation in scientific instrumentation for 27 years. Manufacturing state-of-the-art ion beam systems for labs around the world, they have contributed to research from fields as diverse as cancer research to quantum computers. For more information visit www.ionoptika.com.

1https://www.qureca.com/overview-on-quantum-initiatives-worldwide-update-mid-2021/

IOG C60-20S ion beamIonoptika 2021

C60-20S

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IOG C60-20S Ion Beam
IOG C60-20S Ion Beam
IOG C60-20S Ion Beam

C60-20S

Sputtering and depth profiling ion beam


The C60-20S is a high-performance ion beam designed for sputtering surfaces with minimal damage, and reduced preferential sputtering effects.

Operating at voltages up to 20kV, the C60-20S effectively sputters material with minimal damage without re-deposition of carbon.

Ideal as an upgrade component for XPS, AES, and SIMS, C60 provides uniform sputtering across a wide range of materials.



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Key Features:

  • High current density for faster etching
  • Reduced chemical damage over monatomic beams
  • Uniform sputter rates across different materials and crystal orientations
  • Gate valve for quick and easy servicing
  • Long lifetime source

DetailsKey Features

High-resolution ion column

Pioneer features a mass-filtered ion column, with a 20nm spot size, and operates at up to 30kV. This enables incredibly accurate placement of ions within the substrate, subject to scatter.

Two versions of the ion source are available: a liquid metal source and a duoplasmatron, giving you access to a large number of dopant ions.



Deterministic ion implantation

Detection of implant events is critical to deterministic ion implantation. Up to four high-gain, low-noise detectors enable high-efficiency detection of secondary particles (both ions and electrons), offering detection efficiency of better than 85%.



Nanometer precision stage

The stage is a piezo-driven precision stage, with optical encoders with 1nm precision, and is capable of handling up to a 6-inch wafer. There is also a load lock for fast sample insertion and optical cameras for precision alignment.



Proprietary software

Pioneer is completely software driven, and includes implantation UI, SED imaging, vacuum control and monitoring, stage control, and sample transfer. The software is designed to enable fully automated, overnight operation (for high-noise environments). It also offers alignment to pre-defined sample marks, with better than 20nm accuracy.



High-vacuum system

A 6-inch wafer carrying load-lock enables fast sample insertion while maintaining a consistent high-vacuum in the chamber (< 1x10-8 mbar), while a gate valve on the ion column protects the chamber vacuum and allows sources to be swapped quickly.



High-resolution electron column

A 20nm electron beam is available for high resolution imaging.



Applications of Pioneer

In addition to precision ion implantation at the nanoscale, pioneer can also achieve deterministic single-ion implantation. This means that the instrument provides a versatile platform for doping and implantation with both multiple- and single-ion species. The versatility of pioneer is expected to create an invaluable resource in application areas such as:

  • Quantum Technologies
  • Quantum Device Fabrication
  • Nano-material Doping
  • Photonic systems
  • Memory Devices


Installations

SIMPLE

Ionoptika Ltd installed the first two instrument of its kind at the Surrey Ion Beam Centre in 2018, as part of the Single Ion Multi-species Positioning at Low Energy (SIMPLE) project. Read more about this exciting project here.

P-NAME

Ionoptika Ltd is delighted that our Pioneer system features at the heart of the new PLATFORM FOR NANOSCALE ADVANCED MATERIALS ENGINEERING (P-NAME) at the Henry Royce Institute, Manchester.

High-resolution, low-current ion column for precise placement of ions
Liquid metal or duoplasmatron ion source
Wide range of available dopant ions
Nano-precision stage with up to 6-inch wafer handling capability
Deterministic ion implantation detection system
High-resolution electron column available for non-destructive imaging

A New Single Ion Implantation Tool

A New Tool for Quantum Device Fabrication

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July 10th 2018 — A new single ion implantation tool is launched at the UK National Ion Beam Centre. Part of a 3 year project between Ionoptika and the University of Surrey and funded by the EPSRC, the new instrument will enable researchers to create new quantum devices faster than ever before.

The instrument, named SIMPLE (Single Ion Multi-species Positioning at Low Energy), was launched during the 16th International Conference on Nuclear Microprobe Technology and Applications (ICNMTA2018) held at the University of Surrey (click here to read the press release).

SIMPLE Instrument

SIMPLE instrument installed at Surrey Ion Beam Centre | Photo courtesy Nathan Cassidy.

Quantum Technology

Quantum mechanics – that fascinating and sometimes bizarre theory governing the world of the very small – has enormous potential to revolutionize many aspects of modern technology. More secure digital communication, “quantum safe” cryptography methods, more accurate time measurements, and faster, more powerful computers are all thought possible.

Quantum computers in particular are an exciting prospect — it’s expected that they will be capable of solving problems not currently feasible even by our most powerful super computers. Actually building a quantum computer, however, remains an hugely ambitious challenge.

One design for a quantum bit, or qubit – the basic building block of a quantum computer – was put forward by Bruce Kane in 1998. It involves embedding pairs of donor atoms, such as phosphorous, very close to one another (~ 20 nm) within a silicon lattice. Known as electron-mediated nuclear spin coupling, the idea has been successfully utilized by researchers to fabricate individual qubits.

Qubit device schematic

Schematic of Kane’s proposed electron-mediated nuclear spin coupling qubit device.

Using a scanning tunneling microscope, researchers carefully placed individual P atoms using an atomically sharp tip and by stimulating chemical reactions on an atom-by-atom basis. An incredibly intricate technique, it can take several days of meticulous preparation to create just a single qubit. A remarkable feat, however a faster, more scalable method is clearly required.

Single Ion Implantation

The SIMPLE project was established with this objective – to develop an instrument platform for the reliable fabrication of arrays of qubits, with high speed and high precision, using single-ion implantation.

A well established technique in the semiconductor industry, the principles of large-scale ion implantation can be applied to implant individual ions when the parameters are very carefully controlled. Leveraging Ionoptika’s expertise in ion beam design and detection, an instrument platform was designed that is capable of producing an array of millions of implanted ions in just a fraction of a second.

The need for new quantum fabrication technologies

The need for new quantum fabrication technologies

 

The instrument comprises a highly focused, sub-20 nm mass-filtered ion column, a nano-precision stage, and high-sensitivity single ion implantation detection system. While detecting single ion events with high enough consistency for wide scale production remains a challenge, progress in this area has been encouraging, and confidence is high that this goal will be met. And when it is, it will mark a world first, and will usher in a new era of quantum computing.

 

SIMS-China 2018

The 7th Chinese National Conference on Secondary Ion Mass Spectrometry (SIMS-China VII)

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Ionoptika are delighted to announce we are sponsoring the 7th Chinese National Conference on Secondary Ion Mass Spectrometry (SIMS-China VII), which will be held from 9-12th October, 2018, at the Suzhou Institute of Nano-Tech and Nano-Bionics (SINANO), Chinese Academy of Sciences in Suzhou, China. The conference aims to bring together researchers and practitioners from academia and industry to focus on recent advances in SIMS. We look forward to seeing you there!

Conference website 

FLIG5 Floating Ion Beam System

FLIG® 5

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FLIG 5 Floating Low Energy Ion Beam
FLIG 5 Floating Low Energy Ion Beam
FLIG 5 Floating Low Energy Ion Beam

FLIG® 5

Floating Low Energy Ion Beam


The FLIG® 5 is floating low energy ion beam system designed primarily for use on SIMS depth profiling instruments. It has a floating column which transports O2+ ions at relatively high energy prior to deceleration in the final lens. This enables it to deliver a probe of high current density at beam energies as low as 200 eV. This low energy performance makes the FLIG® 5 a powerful tool for shallow depth profiling.

Highlights

  • Option of O2 or Cs source
  • 200 eV to 5 keV Energy Range
  • Ideal for shallow depth profiling

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DetailsSpecifications

The Need for Low Energy Profiling

The requirement for high depth resolution dynamic SIMS arises from the reduction in device size in the semiconductor industry. With the use of low implantation energies and new technology dependent on delta-doping and sharp interfaces, it is increasingly important to have access to depth profiling techniques which can quantify these structures both accurately and reproducibly.

When profiling with energetic oxygen beams, the kinetic energy of the incident particles is transferred to the near surface region of the sample, creating an altered layer in which atomic mixing has occurred. The depth of this layer is approximately 4nm per keV for an O2+ beam, and this imposes an absolute limit on depth resolution. Hence, it is necessary to use energies well below 1keV for profiling of shallow junctions.

Another important factor in the analysis of shallow implants is the transient region which occurs at the surface and at matrix interfaces. At the beginning of a shallow profile, the ion and sputter yields vary rapidly as probe atoms are incorporated into the analysed surface, and the surface chemistry changes. Similar effects occur at matrix interfaces. While this behaviour persists the depth profile is not quantifiable, and any features lying within the transient will be distorted. The thickness of the region, and hence the amount of lost information, can be reduced by using low impact energies.



The Principle of the Floating Ion Gun

In a conventional ion gun, ions are transported through almost the whole ion-optical column at an energy determined by the anode voltage. Thus, to attain a 250 eV impact energy (on a grounded sample) the anode must be set to 250 V and the beam travels through the column at this energy. At such low energy, space charge effects and aberrations of the wide beam seriously limit the final intensity of the probe and impair the probe shape.

In the floating ion gun, almost all of the column is floated to a negative potential and the beam is accelerated to a more viable transport energy between the extraction region and the final lens. Inside the final lens, the beam is decelerated to the desired impact energy. Thus, for a 250 eV impact energy, the anode is set to 250 V and the float could be -3 kV giving a transport energy of 3.25 keV. This provides a significant reduction in beam aberrations. In the FLIG, the Wien filter electrostatic plates and alignment units (including a bend to reject neutrals) are all referenced to the float voltage.



High Erosion Rate, Even at Low Energy

Shallow junction profiling requires the use of a low energy primary beam in order to minimise the effects of atomic mixing induced by the beam. As sputter yield reduces with lower energies, it is vital that the low energy probe has a high current density. Figure 1 shows characteristic plots of probe size versus beam current for the FLIG 5.

The FLIG 5’s high brightness duoplasmatron source and floating column optics deliver exceptional probe intensity, in comparison with conventional systems, facilitating low energy profiling with acceptable erosion rates.



High Depth Resolution and Dynamic Range

To attain high depth resolution without sacrificing erosion rate, the bottom of the analysis crater must remain flat through the profile. A good probe shape, with minimum aberration tails, is essential to minimise curvature at the sides of the crater. Reducing the extent of this curvature enhances depth resolution and dynamic range, as well as allowing the use of smaller scan fields and hence shorter analysis time.

Current vs spot size for the FLIG

Figure 1. Current vs spot size for the FLIG® 5.

The FLIG’s floating column transports the beam through most of the optics at high energy (generally between 2.5keV and 5keV). This greatly assists in reducing beam spreading in the column and concomitant aberrations in the probe. The result is sub-nanometre depth resolution at low energy, with profiles showing high dynamic range at all energies.

The depth resolution capability is demonstrated in Figure 2, which shows profiles of a Si-Ge superlattice. Grown by MBE, this structure has alternating 1nm layers of Si and Ge. The low energy profile shows a 45% valley between Ge peaks 14 and 15, showing the feature to be easily resolved.

Depth profiles of SiGe lattice

Figure 2. Depth profiles of SiGe lattice

A remarkable feature is the apparent increase in resolution with depth in the low energy profile. A cross-sectional TEM image of the sample revealed that the upper layers were buckled, causing the lower resolution of the top layers.



Ease of Operation

Control of the voltage settings in the FLIG is greatly simplified by the use of a computer software interface. This allows many useful features to be built into software, the most valuable being the facility to save complete sets of operating voltages. Critical control voltages such as extraction and alignment are referenced to other supplies rather than ground to simplify tuning of the column.

The system is ready for use with automated systems which can command a change of preset conditions, when required, using ASCII commands.

Beam Energy Range:200 eV to 5 keV
Max. Current (5 kV):> 500 nA
Min. Spot Size (5 kV, 500 nA):< 15 μm
Max. Current (1 kV):> 350 nA
Min. Spot Size (1 kV, 100 nA):< 25 μm
Max. Current (250 eV):> 250 nA
Min. Spot Size (250 eV, 100 nA):< 50 μm