What is tissue array (TMA)?
Tissue array or tissue microarray (TMA) is an innovation developed in late 90’s in the field of pathology. A TMA is commonly referred to a tissue section cut from a single paraffin or frozen recipient block that contains up to one thousand small representative tissue samples cored and re-assembled from different donor tissue blocks by using a manual or automated arrayer. TMA technology allows high throughput analysis of RNA, DNA or protein molecules in multiple tissue specimens at the same time, which is extremely useful in biomarker research and drug target validation.
How do you design your TMA products?
Following FDA guidelines we design TMA of normal tissue panels for tissue cross-reactivity (TCR) study of therapeutic and diagnostic antibodies. For oncological studies, we have tumor progression TMAs (normally in 96 core format) containing cases of different development phases, grades and stages such as normal to malignant, low grade to high grade, paired normal vs tumor or primary vs metastasis of the same patients (in 24, 48 and some 126 core formats). For large scale profiling of specific tumors, we have appropriate TMAs with over 150 cores , most of which have multiple sets with non-overlapping cases. For more technical information, please Click “here”.
How to understand the names and formats of your TMA products?
Our TMAs have 1.1mm, 1.5mm, 2mm, 2.5mm and 4.5mm core size. The section sizes of our TMAs are designed for easy handling during staining and analysis processes. The first three letters of a TMA name is, in animal, referred to a species, in human, referred to system or anatomic site plus disease. The numbers following the letter indicate core number and set number. For example: “AMS541” indicates animal mouse with 54 cores and set 1. “BRC15010” indicates breast cancer with 150 cores and set 10. “MNO1021” indicates multi-normal organs with 102 cores and set 1. Click “here” for more information.
What clinicopathological information do you provide for the cases used in your TMA?
All human TMAs contain sex, age, anatomic site and pathology diagnosis. Tumor TMAs also contain grade and TNM stage. Only a few TMAs have treatment and follow-up data.
Do you use adhesive tape for transferring tissue sections on your tissue microarray (gene-chip)?
No, we do not use this technology, since it can cause damage to tissue sections. We have our own special technical set-up and skills for cutting TMA sections.
What do you mean by “fresh cut”?
To ensure the freshness and quality, we cut our TMA sections only upon receiving orders, which we refer to as “fresh-cut”.
What are the advantages of fresh-cut vs stocked tissue sections?
Stocked tissue sections may be used for detection of most of the molecules. However, it is well documented that protein molecules can loss their detectability over storage times. This is particularly true for detection of some functional molecules, such as phosphorylated proteins, which requires fresh-cut tissue sections. It is neither easy nor economic to provide fresh cut TMA tissue sections due to the complicated TMA section cutting procedures and significant TMA tissues loss as a result of trimming for each cutting process. To ensure the maximum quality of our product, we provide this important benefit to our customers.
Do you bake your TMA or single tissue sections before shipment?
We routinely dry our tissue sections at 47C for 3 to 8 hours in an oven. It is important to bake the slides at 60C for one hour before IHC or ISH procedures. With instruction from our customers, we can also bake the slides accordingly before shipment.
Do you cover your TMA or single tissue sections with melt paraffin?
For fresh-cut sections, it is not necessary to cover them with melt paraffin. To cover the sections with paraffin, it is necessary to bake the slides at a high temperature, and it is also important to bake the slide again before use in high temperature for extended time to melt down the covering paraffin. Multiple high temperatures baking may reduce the antigeniety of the tissue samples on the slides.
Do you vacuum-seal your TMA slides before shipment?
No, we do not feel it is necessary to vacuum sealed the package of our fresh-cut sections. However, if it is requested by customers, we can do it.
What are the common problems of the TMA products in the market and your solutions to these problems?
The followings are some common problems/limitations of TMA/single tissue sections and our solutions:
Heterogeneity - protein expressions in tumor tissues can be very heterogeneous. A single tissue core may not be representative.
Pantomics solutions – We have TMAs with different core sizes ranging from 1mm to 2.5mm. For TMAs with small cores we make TMAs with duplicated or even triplicate cores, which greatly ensure a good representation of protein expression levels across the cases.
Lack of homogeneous tissue quality – It is very common for TMA vendors to obtain their tissue samples from different sources with different sample storage, fixation and processing conditions. These tissue samples may produce heterogeous results in IHC/ISH detection tests under the same experiment conditions.
Pantomics solutions – We provide our collaborative hospitals with the standard 10% NBF made in our facility for tissue fixation, and all the fixed tissue samples are processed into paraffin-embedded blocks in our dedicated tissue bank with the same SOPs.
Limited supply of the same cases – The TMA or single case products of most vendors may be limited to one block. As a result, they may discontinue their products as soon as the block is run out. It is difficult or impossible for customers who want to come back to the same cases at a late stage of a study or multiple studies.
Pantomics solutions - Because we obtain large fresh tissue samples and process them in our tissue bank, we can make as many blocks as possible for each case. Except for a few TMAs made from small biopsy samples, all of our TMA products have never been discontinued. Some customers can correlate their results obtained 10 years ago with those obtained in their recent studies on the same TMAs or cases. In one study, we provided >10,000 slides for one TMA, ensuring the number 1 slide has the same quality as that of the last slide.
Limited case numbers – Because lack of reliable tissue sample sources, it is not easy for other vendors to organize multiple cases for a large scale study effectively.
Pantomics solutions – We have been collecting tissues from our collaborative hospitals for more than 10 years. Our tissue bank is one of largest private ones, if it is not the largest privately owned tissue bank. In the past few years, we have been able to provide over 1000 single cases of one tumor type for each of large scale studies from some well known pharmaceutical/diagnostic companies.
Overlapping cases – Many vendors distribute TMA or single tissue sections from the same suppliers. Inevitably, they are selling the products made from the same cases that may under different product names.
Pantomics solutions – Pantomics only supplies TMAs or single tissue sections from our own collection. For each of the common tumors, we have multiple sets of TMAs with non-overlapping cases, ensuring genuine individual case numbers for a study.
How should I choose your TMA products?
Tissue arrays are generally expensive reagents. We would like recommend the followings:
- If you have not done IHC or ISH before, it is a good idea to practice the staining on some cheap single tissue sections of the organ that is known to express the marker of your interest or some cheap small TMA, such as our universal TMA, UNC241;
- Use cheap single tissue sections and TMAs, such as UNC241 to optimize your antibody first. Once you have the working conditions for your antibody, you then test the antibody on the expensive TMAs.
- For antibody tissue cross-reactivity test, you can use MNO341, MNO381 or MNO661 for initial tests. You can then move to MNO961 or MNO1021 if you want to follow FDA guidelines.
- For random tumor issue profiling, you can start with MTU481, MTU391 or MTU951. If you identify special patterns of staining in certain types of tumors, you can screen your antibody on TMAs for these tumor types.
- If you want to study common diseases in an organ or system, you can screen your antibody on an organ or system common disease TMA, such as DID381 is for common diseases of the digestive system, BRD961 is for common diseases of the breast.
- If you want to study expression patterns of a biomarker during development and progression of a tumor type, you can try our 96 core series TMAs for the appropriate organ or system.
- If you want to compare expression levels of a biomarker in a normal tissue type and its tumor counterpart from the same individual patients, you can try our normal vs. tumor pairing TMAs for the appropriate organ or system.
- If you want to compare expression levels of a biomarker in a primary tumor type and its metastasis from the same individual patients, you can try our primary tumor vs metastasis TMAs for the appropriate organ or system.
- If you want to conduct large scale screening of a tumor type, please try our TMAs with 150 or more cores;
- If you cannot decide which TMAs you would like to test on, please contact us by email or phone. Our scientist or pathologist will be very happy to help you with your TMA selection.
What is the general core missing rate for your TMA products?
The current industrial high standard for TMA core missing rate is 10%, i.e. 90% of the cores on an array slide should contain recognizable amounts of the target cells. We strictly stick to this standard. If any TMA product has a core missing rate over 10% due to tissue exhaustion, we will inform our customers and give them appropriate discount, or ask them to wait for a new block if there is no back-up block on site. In fact, for most our TMA sections, the missing core rate is below 5%. This together with “fresh-cut” nature makes our TMA products one of the best in the market.
How do you design and validate you IHC control TMAs?
We are aiming to make control TMAs for all the common antibodies that are used for IHC. We initially screen relevant tissue samples (hundreds of cases) with each of ~300 IHC antibodies. We then group the cases into negative, weak, moderate and strong categories for each antibody. Except for few, all the IHC control TMA contains 4 pairs (duplicates) of cores representing negative, week, moderate and strong expressers for appropriate molecules.
Do you follow any guidelines in tissue acquisition?
All the human tissue samples in our tissue bank are collected under strict IRB/HIPPA approved guidelines/protocols with informed consents from the donors or their relatives and the rights to hold research uses for any purpose or further commercialized uses are waived. We try our best to protect the confidentiality of personal information, and make sure that no names and any other identity information are revealed during the process of development of tissue arrays, nor to end users who receive our tissue products. For animal tissue acquisition we also follow IACUC protocols.
How do you fix the tissue samples that you acquire?
We provide our collaborative hospitals with standard 10% NBF. Large tissue samples are sliced in 1cm intervals and put in specimen containers filled with 10% NBF within 30 minutes of surgical removal. After the hospital pathology departments take sufficient tissue samples for their diagnosis, all the samples (soaked in 10% NBF in containers) are immediately transported to our tissue bank where our staff make sure that the samples are sufficiently fixed (fixed for 24 hours or for extended time if the samples show sign of insufficient fixation), and conduct grossing and processing.
How long do you keep tissues unfixed after surgical removal?
Within 30 minutes of surgical removal.
How long do you wait for autopsy tissue samples to be fixed after patient death?
We do not use autopsy tissue samples for our TMA or single tissue sections except for organs that cannot be obtained from surgery, such as brain, heart. The autopsy tissue samples in our tissue bank are collected within 8 hours of death.
How do you process your tissue samples?
We have two Leica TP1020 tissue processors in our tissue bank. One is for large samples; the other is for small biopsy or special tissue samples. All the tissue samples in our tissue bank are processed using SOPs commonly use in Pathology Departments throughout Europe and USA.
How do you ensure that the clinico-pathological data of your cases are correct?
The original diagnosis of each case is provided by the original hospital. After we process the tissue samples into paraffin blocks, we cut sections and stained with H&E for each block. Our in-house pathologists review the histology of each block and record the histology together with the original pathology findings in our database. Our well trained pathologists are responsible for selecting and retrieving cases for our TMA manufacturing. After each TMA product is made, section for each TMA is H&E stained and histology of each core or the TMA is further reviewed by our pathologists. During the section cutting, every 10th section of the tissue array is reviewed again by our pathologists to make sure the correct histology of each core and appropriate core retaining rate of the TMA in use.
How do you ship your tissue array and single tissue sections/slides?
Our TMA and single tissue sections are packed in appropriate slide mailers and wrapped safely in foam packs and shipped in a suitable FedEx box. We normally ship our products via FedEx overnight express.
How long can a tissue array or single tissue section be stored?
There are quite a few studies on stability of paraffin-embedded tissue sections during storage. It is recommended that paraffin tissue sections should be stable at room temperature for 3 to 6 weeks and at 4C for one year. Our experience has shown that for detection of most protein molecules paraffin tissue sections should be stable for at least for six months if they are well-wrapped and stored at 4C. For some detection of functional molecules, such as phosphorylated protein, it is important to use sections cut within a few weeks.
Do you have any favorable IHC/ISH/FISH protocols for your tissue array sections?
IHC/ISH/FISH protocols for TMA sections should be the same as those for whole single tissue sections. For antigen retrieval, it is better to use a mild method and avoid direct boiling and use of high pH solution. Please click supports page and download our IHC/ISH/FISH protocols.
Are there any publications using your TMAs?
Yes, there should be many publications in the literature. You can search Pantomics online or in PUBMED.
Do you make custom TMAs?
Yes, you can contact our Customer Service in the USA: 1-888-231-3180 (toll free) or 1-415-863-2380, or email firstname.lastname@example.org for more details
Do you guarantee the results of my IHC/ISH/FISH tests if I use your TMA or single tissue sections?
Many factors determine the outcomes of IHC/ISH/FISH experiments. It is not possible for anyone to guarantee your experiment results when multiple reagents and suppliers are involved. However, you can call us and our experts will be happy to share with you their experiences in using TMA sections.
Are your formalin-fixed, paraffin-embedded TMA and single tissue sections bio-hazards?
After formalin fixation, chemical/heat dehydration and paraffin-embedding, our paraffin-embedded tissue blocks, sections and tissue arrays are considered non-hazardous, although the chemical, physical, bio-hazardous and toxicological properties of these products have not been thoroughly investigated.
What are the advantages of your TMA products over those of other vendors?
The main advantages are:
- Freshly cut TMA sections- cut upon receiving your order;
- Optimal fixation: Collect and fix tissue samples from fresh in standard 10% NBF that we provide to our collaborative hospitals following strict guidelines;
- Uniform quality for each tissue core in any TMA - Our tissue samples are fixed, processed, embedded and stored using the same SOPs. They are all from our dedicated tissue bank facility.
- Reliable diagnosis - Pantomics was found by a pathologist. It is also managed by pathologists. We also have an expert board consisting of many experienced pathologists.
- Lasting supply of the same TMA, because our comprehensive tissue bank
- Provide single tissue sections of selected cores in most of our TMA products.
What services do you provide?
As listed on our website, we provide a wide range of services from tissue processing, custom array construction, various staining, image analysis and various contracted protracts. Please contact our Customer Service in the USA: 1-888-231-3180 (toll free) or 1-415-863-2380, or email email@example.com for more details
How do you manage your service project?
After receiving your order and required materials, we will assign a project number and a manager for your project. He or she will be responsible for coordination, monitoring up the progress and organizing all the data for the project. Please contact our Customer Service in the USA: 1-888-231-3180 (toll free) or
1-415-863-2380, or email firstname.lastname@example.org for more details
What is the turn-around time for your services?
It depends on the scale of a project. It may take one week to few months to get the project done. Please contact our Customer Service in the USA: 1-888-231-3180 (toll free) or 1-415-863-2380, or email email@example.com for more details